Evaluation of the Sensitivity and Specificity of a Novel Quality of Life (QoL) Tool to Assess the Treatment Satisfaction in Psoriasis Patients
Conditions: Psoriasis
Sponsor: Clinact

Non-Interventional Study Protocol 
Study Short Title  
Evaluation of the sensitivity and specificity of a novel quality of life (QoL) 
tool to assess the treatment satisfaction in psoriasis patients 
STUDY IDENTIFICATION No. 2020-A00652-37 
Full Study Title 
Evaluation of the sensitivity and specificity, compared to DLQI as a standard tool, of a novel 
QoL questionnaire (treat to the PSOriasis patient satiSfactiOn TARGET) among moderate to 
severe psoriasis patients treated with brodalumab (Kyntheum®) 
GPP statement:  
This Non-Interventional Study will be conducted in compliance with the 
Clinical Study Protocol, Good Pharmacoepidemiology Practices and 
applicable regulatory requirement(s). 
Sponsoring entity: 
LEO Pharma France  
LEO Study ID: PSO-TARGET 
2 rue René Caudron  
215 avenue Georges Clemenceau 
78960 Voisins-Le-Bretonneux 
 
Date: 25-05-2020 
 
Version: 2.0 
 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 2 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
KEY STUDY PERSONNEL 
STUDY MANAGER 
BERTRAND Bénédicte, Clinical Manager 
 
CLINACT  
Vélizy Espace – Immeuble Santos Dumont 
13 avenue Morane Saulnier – CS 50730 
78457 Vélizy-Villacoublay Cedex, France 
 
MAIN PROTOCOL AUTHOR 
SALTET DE SABLET Thibaut, Medical Writer 
 
CLINACT 
Vélizy Espace – Immeuble Santos Dumont 
13 avenue Morane Saulnier – CS 50730 
78457 Vélizy-Villacoublay Cedex, France 
 
STATISTICIAN 
CARRERE Florence, Head of Biometry / 
Senior Biostatistician 
 
STATITEC 
Vélizy Espace – Immeuble Santos Dumont 
13 avenue Morane Saulnier – CS 50730 
78457 Vélizy-Villacoublay Cedex, France 
 
 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 3 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
APPROVERS 
The following person(s) within LEO Pharma (LEO) has/have approved this Study Protocol by 
signing the Non-Interventional Study Protocol Approval Form adjoined as a separate page to 
this document: 
Nadine MacKenzie 
 
Medical director, France and Benelux  
 
 
 
 
Sarah Moumane 
 
Dermatology MSL manager, France 
 
 
Angèle GUILBOT 
 
Scientific and Regulatory Director 
CLINACT 
Vélizy Espace – Immeuble Santos Dumont 
13 avenue Morane Saulnier – CS 50730 
78457 Vélizy-Villacoublay Cedex, France 
 
 
Dr Ziad REGUIAI 
 
International Co-ordinating Investigator  
Polyclinique Reims-Bezannes 
89 Rue Victor De Broglie 
51430 Bezannes, FRANCE 
 
 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 4 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
1 
Table of Contents 
 
1 Table of Contents ................................................................................................................... 4 
2 List of Abbreviations .............................................................................................................. 7 
3 Responsible Parties ................................................................................................................ 8 
4 Abstract ................................................................................................................................ 10 
5 Amendments and Updates .................................................................................................. 15 
6 Milestones ........................................................................................................................... 16 
7 Rationale and Background ................................................................................................... 16 
8 Research Question and Objectives ...................................................................................... 20 
 Primary Objective ............................................................................................................ 20 
 Secondary Objectives ...................................................................................................... 20 
9 Research Method ................................................................................................................. 20 
 Study Design .................................................................................................................... 20 
 
Eligibility criteria .......................................................................................................... 20 
 
PSO-TARGET Quality of Life Component grid. ............................................................. 21 
 
Dermatology Quality of Life Index (DLQI) .................................................................... 22 
 
Limitation of bias ......................................................................................................... 23 
 
Study Schedule ............................................................................................................ 23 
 
Definition of a non-interventional study ..................................................................... 24 
 Setting .............................................................................................................................. 25 
 Variables .......................................................................................................................... 26 
 Data Source ..................................................................................................................... 28 
 Study Size ......................................................................................................................... 29 
 Data Management ........................................................................................................... 30 
 Data Analysis ................................................................................................................... 32 
 Statistical Analysis Plan .................................................................................................... 32 
 
Description of the population ..................................................................................... 32 
 
Baseline characteristics ............................................................................................... 33 
 
Sensitivity/sensibility analysis ..................................................................................... 33 
 
Efficacy analysis ........................................................................................................... 35 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 5 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 
Other secondary analyses ........................................................................................... 36 
 
Safety analysis ............................................................................................................. 39 
 Quality Control ................................................................................................................ 39 
 
Data Collection ............................................................................................................ 39 
 
Data monitoring ........................................................................................................... 39 
 
Data validation ............................................................................................................. 40 
 Limitations of Research Methods .................................................................................... 40 
 Other Aspects .................................................................................................................. 41 
10 Protection of human subjects ............................................................................................. 41 
11 Management and Reporting of Adverse Events and Other Experiences ............................ 44 
 Definitions ....................................................................................................................... 44 
 Physician’s responsibility for reporting of Adverse Drug Reactions, Adverse Events and 
Other Experiences ........................................................................................................... 45 
 LEO responsibilities for reporting of safety-related data ................................................ 47 
12 Plans for Disseminating and Communicating Study Results ............................................... 47 
13 References ........................................................................................................................... 48 
Annex 1. PSO-TARGET Component Grid ................................................................................... 51 
 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 6 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
APPENDICES 
1. 
PSO-TARGET Component grid 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 7 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
2 
List of Abbreviations 
ADR: 
Adverse Drug Reaction 
AE: 
Adverse Event 
CRF: 
Case Report Form 
CRO: 
Contract Research Organization 
DLQI: 
Dermatology Quality of Life Index 
HCP: 
Healthcare Practitioner 
IEC: 
Independent Ethics Committee 
IRB: 
Institutional Review Board 
LEO 
LEO Pharma A/S and/or affiliates or representatives  
MedDRA: 
Medical dictionary for Regulatory Activities  
NIS: 
Non-Interventional Study 
OE: 
Other Experience 
PASI: 
Psoriasis Area and Severity Index  
PRO: 
Patient Reported Outcome 
QoL: 
Quality of Life 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 8 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
3 
Responsible Parties 
Sponsor : LEO pharma France 
2 Rue René Caudron 
78960 Voisins-le-Bretonneux 
France 
 
Study Sponsor Contact: Yassmina Mandouri  
2 Rue René Caudron, 
78960 Voisins-le-Bretonneux 
Email yamfr @leo-pharma.com 
 
Contract Research Organization: CLINACT 
Vélizy Espace, bâtiment Santos Dumont 
13 Avenue Morane Saulnier 
78140 Vélizy-Villacoublay 
 
Coordinating Investigator: 
Dr Ziad REGUIAI 
Polyclinique Reims-Bezannes 
89 Rue Victor De Broglie 
51430 Bezannes, FRANCE 
 
 
Scientific committee: 
Dr Pierre-Dominique GHISLAIN 
Cliniques Universitaires Saint Luc – Université Catholique de Louvain 
Avenue Hippocrate 10, 
1200 Woluwe- Saint-Lambert 
Dr Thierry BOYE 
Hôpital d'Instruction des armées SAINTE ANNE (TOULON) 
BCRM TOULON 2 boulevard Sainte Anne BP 600 – 83800 TOULON Cedex 9 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 9 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Dr Ziad REGUIAI 
Polyclinique Reims-Bezannes 
89 Rue Victor De Broglie 
51430 Bezannes, France 
 
LEO Pharma legal entity is the sponsor of the study and the Contract Research Organisation(s) 
(CRO) CLINACT is authorised by LEO to act on behalf of LEO. LEO Pharma 2 Rue René Caudron, 
78960 Voisins-le-Bretonneux, France will be the Data Controller. 
Contact and responsibilities of all parties contributing to the study, including all investigators, 
are detailed in a stand-alone document available upon request to LEO. For key contributors, 
e.g. national coordinating investigators, LEO will keep CVs and documentation regarding 
Conflicts of Interest and make such documentation available upon request from relevant 
parties, e.g. authorities, journals. LEO will keep a record of all relevant sponsor personnel. 
CLINACT will keep a record of all involved CRO personnel. 
The following essential documents must be in the hands of LEO before the study is initiated at 
a site: 
 Written agreement between LEO or CLINACT and the Study Site Responsible / Clinic / 
Hospital. 
 Signed and dated protocol agreement and amendment agreements, if any, with the 
original signature of the Site Responsible. 
 Patient Information Sheet and Informed Consent Form in local language (notified to / 
approved by Independent Ethics Committees (IECs). 
 Written IEC / IRB approval. 
 Competent Authority notification. 
 Product liability insurance. 
 LEO safety plan which is a three party agreement between Global safety, Safety contact 
person and the CRO on the handling of safety reporting 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 10 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
4 
Abstract 
Title 
Evaluation of the sensitivity and specificity, compared to DLQI as a standard tool, of a novel 
QOL questionnaire (treat to the Patient satiSfactiOn TARGET in Psoriasis patients) among 
moderate to severe psoriasis patients treated with brodalumab (Kyntheum®) 
 
Rationale and background 
The severity of psoriasis can be influenced by a great variety of factors including extent of the 
disease, lesions location and impact on quality of life. The current standard of care for psoriasis 
is focusing on the reduction of the skin symptoms as defined by the PASI, somewhat setting 
asides the patient’s feelings in terms of which aspects of his/her life are affected by the 
disease. Despite the fact that multiple patient reported outcomes (PRO) questionnaires are 
available to evaluate the impact of the disease on patients’ quality of life, only few items 
address the subjective impact of skin disease. Among the available PROs the Dermatology Life 
Quality Index (DLQI) is the most frequently used. It is a standardized tool designed to cover a 
broad range of dermatologic afflictions but lacks specificity towards the effect of psoriasis on 
quality of life. The DLQI is composed of ten questions grouped in 6 domains “symptoms and 
feelings”, “daily activities”, “leisure”, “work/school”, “personal relationships” and “treatment”. 
Each answer is graded from 0 to 3. The DLQI score is calculated by adding the score of each 
question, resulting in a maximum score of 30 and a minimum of 0. The higher the score, the 
more quality of life is impaired. A score higher than 10 indicates that the patient's life is being 
severely affected by their skin disease.  
Because of its limitations, some patients cannot seem to completely restore a normal quality 
of life (e.g. DLQI 0-1) even though their reached a perfect PASI score (100). This phenomenon 
may be explained by the fact that the patient’s own perception can be different from the 
physician’s perspective and may have changed in time, between follow-ups. These are as many 
reasons as why it is highly difficult to accurately fathom the therapeutic expectations of the 
psoriasis patients. The standard tools currently in use are not able to assess the perception of 
the disease by the patient its evolution over time. In addition, it is widely recognized that 
alexithymia is more prevalent in the psoriasis patients than in the general population and 
patients with alexithymia appear to suffer higher psoriasis burden as they have more 
difficulties to express their expectations. Since patients struggle to recognize and verbalize 
their emotions, it can be useful and informative to offer patients a variety of verbatim in which 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 11 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
they can identify. PSO-TARGET is an exploratory observational, non-interventional study 
aiming to evaluate a novel approach of assessing psoriasis patients’ satisfaction towards their 
biologic treatment from a quality of life standpoint by using a psoriasis-specific Quality of Life 
assessment grid. 
 
Research question and objectives 
The aim of this exploratory study is to evaluate the sensitivity and specifity of the PSO-
TARGET QoL Component grid as part of a new approach for assessing the level of achievement 
of the psoriasis patient’s therapeutic goal, identified by himself, after a treatment with 
Kyntheum®. This tool will be, if validated, used by physicians to devise a “Treat to patient 
satisfaction target” strategy that better suits their patients’ expectations.  
To construct this new questionnaire, the first step was to collect psoriasis patients’ 
feedback on what is the aspect of their life that is the most impacted by the disease and which 
is the one they would want to improve the most. To this aim, a retrospective survey based on 
the recollection and experience from three clinical dermatologists (two French and one 
Belgian) of patient’s expectations, has been conducted. The results of the survey have been 
used to analyse the type of expectations provided by the patients. Based on that analysis, the 
expert dermatologists generated a grid containing 12 therapeutic goals equally distributed into 
the four major psychometric components classically used in quality of life studies in patients 
with chronic diseases (physical, subjective, relational/social and therapeutic). The proposed 
verbatim was then reviewed by a psychologist to ensure that there was a balance between the 
proposals; i.e. the vocabulary used was neutral enough not to guide the choices. This first step 
has therefore given rise to a QoL component grid that will be administered to the patients 
prior to the initiation of a systemic treatment (Kyntheum® / brodalumab) to set up a main 
objective for the upcoming treatment. At 12-16 weeks the patient will be asked to rate his/her 
level of satisfaction in regard to the treatment objective defined prior to treatment initiation 
using a four-point Likert scale (“very satisfied”, “satisfied”, “unsatisfied”, “very unsatisfied”). In 
order to evaluate the sensitivity and specificity of, the PSO-TARGET QoL component grid, the 
patient will be asked to fill in, prior the treatment introduction and during the follow up visits, 
the DLQI questionnaire. The primary objective of the study will be to estimate the level of 
concordance of this satisfaction level based on the PSO-TARGET QOL tool and the reference 
method in Quality of Life for psoriasis patients; i.e. the DLQI, at the same time point. This aim 
will be reached by comparing, at 12-16 weeks, the DLQI and the satisfaction level given by 
patients in regard to their own treatment objective defined at baseline using the PSO-TARGET 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 12 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
QoL component grid. True Positive (TP), False Positive (FP), True Negative (TN) and False 
Negative (FN) will be defined using a contingency table. These quantitative variables will be 
used to calculate the sensitivity (proportion of actual satisfied patients that are correctly 
identified as such) and specificity (proportion of actual unsatisfied patients that are correctly 
identified as such) of the PSO-TARGET QoL Component grid, compared to the quality of life 
given by the DLQI. If these metrics reach a certain threshold (85%), the PSO-TARGET QoL 
component grid will be considered for additional studies in order to validate it at a larger scale 
and further demonstrate it is as much sound in assessing the patients’ quality of life as the 
DLQI. 
Because of the fact that alexithymia is highly prevalent in psoriasis patients, the grid will 
be administered to the patient after he/she had spontaneously expressed his/her treatment 
expectations. This should help the patient to narrow down the specific goal where his/her 
expectation belongs. In addition, as part of a secondary objective the treating physician will 
also choose an item from the table based on what he/she perceives in terms of patient’s 
expectations without disclosing it to the patient. This will allow us to evaluate the level of 
accordance between the physician-chosen and the patient-chosen therapeutic goal. As 
another secondary endpoint, the level of achievement of the therapeutic goal will be assessed 
at 12/16 weeks and followed-up for 52 ± 4 weeks. Patients scoring the treatment as “satisfied 
or very satisfied” will be considered as having achieved their therapeutic goal. Another 
endpoint of interest (secondary) will be to assess, after 12/16 weeks of treatment, if the 
patient chooses a new therapeutic goal, different from the one he initially defined. 
It is important to note that, this study being observational, none of the visits (baseline 
and follow-ups) are specific to the trial but part of the dermatologists’ standard of care in both 
countries (France and Belgium). In addition, in order to limit variability in terms of treatment 
profiles (dosage and administration schedule) and thus to keep the study population as 
homogenous as possible, it has been decided to include only patients treated by Kyntheum®, 
in other terms Kyntheum® treatment is an accessory to the study but PSO-TARGET will not 
assess Kyntheum® efficacy per se. 
The study objectives are the following: 
Primary objective: 
Assess at week 12/16, post biologic treatment, the sensitivity and the specificity, compared to 
DLQI as a standard tool, of the PSO-TARGET QoL component grid as a novel approach aiming 
to evaluate the patients’ satisfaction with regard of their treatment. 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 13 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Secondary objectives: 
- 
Evaluate at week 12/16, post Kyntheum® treatment, the percentage of patients who has 
achieved the main treatment goal they identified in the QoL component grid at baseline. 
- 
Identification of predictive factors (among baseline characteristics) of the achievement 
of the main treatment goal; 
- 
Evaluate the level of agreement between the dimensions reported by the patient and by 
the treating physician; 
- 
Evaluate at 52 weeks the percentage of patients for whom the therapeutic objective 
initially achieved at the 1st follow-up visit is still maintained; 
- 
Evaluate the percentage of patients who change their therapeutic objective after 12/16 
weeks of treatment; 
- 
Follow the evolution of the PASI score (at 12/16 and 52 weeks); 
- 
Level of accordance between PASI 90/100 and the satisfaction level in regard to the 
therapeutic objective set by the PSO-TARGET QoL Component grid; 
- 
Follow the evolution of the DLQI score (at 12/16 and 52 weeks). 
 
Study design 
PSO-TARGET is an observational, non-interventional, prospective, multicentric, 
international, European study requiring no change in the patients’ standard of care (RIPH3 in 
France). 
Population 
Adult patients suffering from moderate to severe psoriasis vulgaris for whom the 
dermatologist decided to prescribe a treatment with Kyntheum®. 
Variables 
Primary endpoint 
- 
At 12/16 weeks, level of concordance between the satisfaction level in regard to the 
therapeutic objective set by the PSO-TARGET QoL Component grid and the DLQI in 
assessing the impact of the treatment on the patients’ quality of life. 
Secondary endpoints 
- 
At week 12/16, post Kyntheum® treatment, the percentage of patients who achieved the 
main treatment goal identified by the patient himself in the QoL component grid at 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 14 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
baseline. The therapeutic objective achievement is defined as “satisfied” or “very 
satisfied” response on 4 points Likert scale. 
- 
Level of concordance between the satisfaction level in regard to the therapeutic 
objective set by the PSO-TARGET QoL Component grid and the DLQI at the 2nd follow-up 
visit (52 ± 4 weeks.). 
- 
Research of predictive factors (among baseline characteristics) of the achievement of the 
main treatment goal. 
- 
Percentage of agreement between the physician-reported and the patient-reported 
dimensions at the first follow-up visit. 
- 
Rate of patients having changed objective at the 1st follow-up visit (12/ 16 weeks). 
- 
Percentage of patients who have maintained at 52 ± 4 weeks the level of satisfaction 
achieved at the 1st follow-up visit. 
- 
PASI Scores at baseline, at the 1st follow-up visit (12/ 16 weeks), at the 2nd follow-up visit 
(52 ± 4 weeks.). 
- 
Level of accordance between PASI 90/100 and the satisfaction level in regard to the 
therapeutic objective set by the PSO-TARGET QoL Component grid. 
- 
DLQI Scores at baseline, at the 1st follow-up visit (12/ 16 weeks), at the 2nd follow-up visit 
52 ± 4 weeks. 
 
Data sources 
Patients’ data will be collected at day 0, at the 1st follow-up visit (12/16weeks) and at the 
2nd follow-up visit at 52 ± 4 weeks according to the physician’s practice. 
As a prospective study, the following data will be collected during the patient visit: 
disease history, concomitant treatments, previous anti psoriatic treatment and adverse events. 
In addition, the following study specific data will be collected: disease severity (PASI score), 
quality of life questionnaires (DLQI, PSO-TARGET component grid). 
 
Study size 
The main criterion is the sensitivity of the PSO-TARGET tool (percentage of patients who 
consider their target objective as being achieved after 12/16 weeks of treatment as defined 
by a “satisfied or very satisfied” response, assessed on a 4 points Likert scale, among patients 
with a DLQI total score of 0 or 1). 
The sample size calculation is based on the following hypotheses : 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 15 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 Sensitivity : 90%  
 Absolute precision : 10% 
 Type I error : 5% 
 Power at 80%  
 Prevalence: 80% (estimated rate of patients with a DLQI 0-1 after 12 weeks of 
treatment. 
Based on these hypotheses, the sample size needed is estimated at 134 evaluable patients. 
Assuming 10% of patients will not be evaluable on main criterion, 150 patients have to be 
included. 
 
Data analysis 
Analysis of the primary endpoint 
The performance of the PSO-TARGET QoL component grid to assess the treatment impact on 
the patients’ quality of life will be determined by calculating the sensitivity and specificity of 
the grid compared to the DLQI (reference). The grid will be validated if both the specificity and 
sensitivity parameters reach the 85% threshold. 
 
Milestones 
Regulatory Submissions: Q2 2020 
Start of data collection Q3 2020  
End of data collection Q2 2022 
Final report Q4 2022 
5 
Amendments and Updates 
None 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 16 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
6 
Milestones 
Planned dates for study milestones are indicated in the table below: 
 
Milestone 
Planned Date 
Start of data collection 
Q3 2020 
End of data collection 
Q2 2022 
Final study report 
Q4 2022 
 
The start of the study is defined as the date on which the first information on a study patient 
is recorded in the study dataset. LEO will ensure that End-of-Data Collection (End of Study) 
notification is submitted to the concerned authorities and IECs for each site, for each country 
and for the complete study. 
Based on upcoming knowledge, LEO might choose to terminate the study prematurely. In such 
case the Committee(s), study sites, IECs and authorities will be informed promptly. 
 
7 
Rationale and Background 
Psoriasis is a chronic, immune-mediated inflammatory skin disease. Clinical manifestations of 
psoriasis can be of multiple forms, including, among others, plaque psoriasis, guttate psoriasis, 
palmoplantar psoriasis, and pustular psoriasis (Lebwohl, 2018). Psoriasis is characterized by an 
abnormal keratinocyte proliferation in the interfollicular epidermis along with an infiltration 
of antigen-presenting cells and release of pro inflammatory cytokines, leading to a local 
inflammation (Ippagunta et al., 2016; Lowes et al., 2007). The aetiology of the disease is not 
fully understood, but a number of risk factors are recognized, including family history and 
environmental risk factors, such as smoking, stress, obesity, and alcohol consumption (Huerta 
et al., 2007). The prevalence of psoriasis is difficult to evaluate with precision but is estimated 
around 2-4% in western countries (Gelfand et al., 2005; Kurd and Gelfand, 2009; Stern et al., 
2004). In France, the prevalence of psoriasis is estimated to 4,4 % (Richard et al., 2018). 
Psoriasis causes considerable psychosocial disability and has a major impact on patients’ 
quality of life (Krueger et al., 2001). 
The severity of psoriasis can be influenced by a great variety of factors including extent of the 
disease, inflammation, lesions location and impact on quality of life. As those factors can 
fluctuate over time, so can the intensity of the disease and more importantly the patient’s 
perception of his/her affliction. The current standard of care for treatment of psoriasis is 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 17 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
primarily focusing on the reduction of the skin symptoms as defined by the Psoriasis Area 
Severity Index (PASI), somewhat setting asides the patient’s feelings in terms of which aspects 
of his/her life are affected by the disease. Indeed, a multinational study has already shown 
that a discrepancy exists between the physician’s assessment of the disease severity and the 
patient’s (van de Kerkhof et al., 2015). This could be, at least partially, explained by the use of 
standardized tools, by the physician which not necessarily take into consideration the patients 
therapeutic expectation which could sometimes be a subjective parameter. (van de Kerkhof 
et al., 2015). Currently, the higher efficacy observed with new biologics means that PASI 90 or 
even PASI 100 response are increasingly being considered as a new treatment goal (Daudén et 
al., 2016; Kerdel and Zaiac, 2015; Lebwohl et al., 2015). However, other quality of life aspects 
of chronic affections such as psoriasis that are not being assessed by tools like the PASI, must 
not be overlooked Multiple patient reported outcomes (PRO) questionnaires are available to 
evaluate the impact of the disease on patients’ quality of life. Among the available PROs, the 
Dermatology Life Quality Index (DLQI) is the most frequently used (Puig et al., 2017). It is 
composed of ten questions grouped in 6 domains “symptoms and feelings”, “daily activities”, 
“leisure”, “work/school”, “personal relationships” and “treatment”. Each answer is graded 
from 0 to 3. The DLQI is calculated by adding the score of each question, resulting in a 
maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. 
A score higher than 10 indicates that the patient's life is being severely affected by their skin 
disease (Finlay and Khan, 1994). However, the DLQI is a standardized tool which missing 
potentially some quality of life specific issues for psoriasis patient. Consequently, among 
patients, some cannot seem to completely restore a normal quality of life (DLQI 0-1) even 
though they reached a perfect PASI score (100). This phenomenon may be explained by the 
fact that the patient’s own perception can be different from the physician’s perspective and 
may have changed between follow-ups. Although, the Patient Benefit Index has been devised 
to allow the patient to weigh the therapeutic goals in order to define which ones are the most 
important for him/her (using a 4 points Likert Scale, (Augustin et al., 2008)), it is not 
discriminatory enough towards the patient’s principal expectation (Feuerhahn et al., 2012). 
In addition, it is widely recognized that alexithymia (difficulty to express emotion) is more 
prevalent in the psoriasis patients than in the general population and psoriasis patients with 
alexithymia appear to suffer higher psoriasis burden as they have more difficulties to express 
their expectations (Sampogna et al., 2017). Since these patients struggle to recognize and 
verbalize their emotions, it can be useful and informative to offer patients a variety of verbatim 
in which they can identify. Taken together these elements plea for a novel approach that take 
more into consideration the patient’s expectations prior to treatment initiation and not only  

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 18 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
the dermatologist symptomatic approach. We therefore believe that it is of importance to 
assess the 4 components of quality of life usually impacted in case of chronic disease as 
defined by Chassany (Chassany, 2003; Forestier et al., 2019), before initiating the systemic 
treatment, in order to define better therapeutics goals in an holistic approach. It is necessary 
to assess this new approach in a homogenous population, thus only patients starting a biologic 
treatment by Kyntheum® at the inclusion in the study will be enrolled. Indeed, satisfaction 
towards a treatment may be influenced by several factors including administration regimen.  
 
The aim of this study is to evaluate, compared to the DLQI as a standard tool, the 
sensitivity and specificity of the PSO-TARGET QoL Component grid as a new QoL questionnaire 
for assessing the level of satisfaction of the psoriasis patients in achieving the therapeutic goal, 
identified by himself, after a biologic treatment. This study is the first step of an evaluation 
process aiming to validate the PSO-TARGET QoL Component grid. Ultimately, this tool will be 
used by physicians to devise a “Treat to patient satisfaction target” strategy that better suits 
their patients’ expectations. To construct this new questionnaire, the first step has been to 
collect psoriasis patients’ feedback on what is the aspect of their life that is the most impacted 
by the disease and which is the one they would want to improve the most. To this aim a 
retrospective survey based on the recollection and experience from 3 clinical dermatologists 
(2 French and 1 Belgian) of patient’s expectations, was conducted. The results of the survey 
have been used to generate a table containing 12 treatment goals equally distributed into the 
4 major  components classically used in quality of life studies in patients suffering from chronic 
diseases (physical, subjective, relational/social and therapeutic) (Chassany, 2003; Forestier et 
al., 2019). The proposed verbatim was then reviewed by a psychologist to ensure that there 
was a balance between the proposals; i.e. the vocabulary used was neutral enough not to 
guide the choices. This component grid will be administered to the patients prior to the 
initiation of a systemic treatment (Kyntheum® / brodalumab) to set up the main therapeutic 
objective (1 out of 12) fitting with his priority expectation from the upcoming treatment. The 
patient will only have access to the 12 treatment goals but not to the category headings. 
Because of the fact that alexithymia is highly prevalent in psoriasis patients, the grid will be 
submitted to the patient after he/she had been asked by the physician to express 
spontaneously his/her treatment expectations. This should help the patient to narrow down 
the item where his/her expectation belongs. At the 1st follow-up visit (12/16 weeks), the level 
of achievement will be assessed using a 4 points Likert scale (“very satisfied”, “satisfied”, 
“unsatisfied”, “very unsatisfied”). In order to evaluate the sensitivity and the specificity of the 
PSO-TARGET QoL component grid, the primary objective of the study will be to estimate the 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 19 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
level of concordance of this satisfaction level and the overall quality of life as defined by the 
DLQI at the same time point. It is important to consider that systemic treatment by Kyntheum® 
is an accessory to the study but the objective of the PSO-TARGET is not to evaluate Kyntheum® 
efficacy. 
As part of secondary objectives, in parallel to that initial assessment by the patient, the 
physician will tick on the grid what would be his patients therapeutic goal based on what he 
knows/understands from the patient’s disease history and therapeutic desires. At the time of 
his/her assessment, the physician will be blinded of the patient’s choice of therapeutic goal. 
The accordance between the physician-chosen and the patient-chosen dimensions will be 
analyzed. The 12 items of the tool will be pooled and analysed by component (physical, 
subjective, relational and therapeutic). At 52 weeks, among other secondary endpoints, the 
maintenance of the level of achievement of the initial objective observed at the 1st follow-up 
visit, will be assessed. 
One of the innovative aspects of this exploratory observational study will be the 
administration of a psoriasis-specific quality of life component grid containing 12 treatment 
objectives grouped in the 4 quality of life components/dimensions usually impacted in patients 
suffering from chronic diseases (Chassany, 2003; Forestier et al., 2019). Those dimensions 
accounting for the burden to bear when suffering from a chronic disease are the following: 
Physical, Subjective, Relational/Social and Therapeutic. Each dimension will include 3 patient’s 
therapeutic goal based on dermatologists’ clinical experience and reviewed by an expert on 
psychometric tools. 
This is an exploratory study, a first step to assess the interest of the PSO-TARGET component 
grid. If the sensitivity and specificity reach an acceptable threshold (85%), the potential of the 
PSO-TARGET grid will be considered for validation in larger clinical studies. Indeed, more 
studies will be needed to test other attributes in order to fully validate the PSO-TARGET grid 
as an alternative to the DLQI for QoL assessment. Once the PSO-TARGET component grid is 
validated, it will prove to be a useful tool for a better design of a therapeutic objective from 
the physician and thus a better care brought to the patient which should improve the patient’s 
satisfaction and treatment adherence.  

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 20 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
8 
Research Question and Objectives  
 Primary Objective 
The primary endpoint will be the evaluation at week 12/16 of the sensitivity and the specificity, 
compared to the DLQI as a standard, of the PSO-TARGET QoL component grid to assess the 
level of satisfaction of patient achieving the therapeutic goal, identified by himself. 
The therapeutic objective will be considered as achieved if the patient gives the responses 
“Satisfied” or “Very Satisfied” on the Likert scale. The response will then be compared to the 
DLQI score at 12/16 weeks. 
 Secondary Objectives 
- 
Evaluate the percentage of patients who consider their target objective as being achieved 
after 12/16 weeks of treatment as defined by a “satisfied or very satisfied” response. 
- 
Level of concordance between the satisfaction level in regard to the therapeutic 
objective set by the PSO-TARGET QoL Component grid and the DLQI at the 2nd follow-up 
visit (52 ± 4 weeks.). 
- 
Evaluate the level of agreement between the dimensions reported by the patient and by 
the treating physician at baseline. 
- 
Follow the degree of completeness of the main treatment goal identified at baseline after 
52 weeks. 
- 
Follow evolution of the PASI score (at 12/16 and 52 weeks). 
- 
Level of accordance between PASI 90/100 and the satisfaction level in regard to the 
therapeutic objective set by the PSO-TARGET QoL Component grid. 
- 
Follow evolution of the DLQI score (at 12/16 and 52 weeks). 
- 
Evaluate the rate of patients who change their therapeutic objective after 12/16 weeks 
of treatment. 
9 
Research Method 
  Study Design 
 
Eligibility criteria 
The inclusion criteria are the following: 
 Age > 18 years 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 21 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 Patient for whom the dermatologist decided to initiate a treatment by Kyntheum® 
according to SmPC. 
 Patient who signed an informed consent. 
 
The following non-inclusion criteria will be applied: 
 Vulnerable subjects according to the law; 
o pregnant, parturient or breast feeding women; 
o deprived of their freedom by administrative, medical or legal decision or 
who is under trusteeship/guardianship; 
o legally protected, or unable to express their consent to participate; 
o With no affiliation to a social security system; 
 Psychologically/linguistically unable to express their consent to participate; 
 With an hypersensitivity to at least one of the excipients of Kyntheum®; 
 Participating at the same time in another clinical trial. 
 PSO-TARGET Quality of Life Component grid. 
As a first step to construct the component grid, a retrospective survey based on the 
recollection and experience from 3 clinical dermatologists (2 French and 1 Belgian) of patient’s 
expectations, has been conducted. The results of the survey have been used to generate a grid 
containing 12 therapeutic goals equally distributed into the 4 major psychometric components 
classically used in quality of life studies in patients suffering from chronic diseases (Chassany, 
2003; Forestier et al., 2019). These four dimensions (cf table 1) are the following: 
- Physical: autonomy, physical capabilities, ability to perform daily activities; 
- Subjective: linked to experienced emotion, anxiety, well-being; 
- Relational/social: with family, friendship or professional environment, engaging 
personal relationships, involvement in social or leisure activities; 
- Therapeutic: linked to treatment, for ex. treatment-/care-related discomfort. 
The investigators participating to the study will agree to implement this table as part of their 
standard of care along with the DLQI questionnaire. 
 
Table 1: Quality of Life (QoL) component grid 
Physical 
Subjective 
Relational/ social 
Therapeutic 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 22 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Not be 
limited/handicaped by 
the pain 
Think less or not at all about 
the disease  
Spend quality time with family, 
friends or colleagues 
Need to think less about 
treatment and care 
Do not feel any 
functional discomfort 
(itching, rash) in my 
daily activities 
Do not feel any anxiety from 
the disease 
Not caring about what people think 
about me 
Encounter very few, if any, 
drug discomfort  
Have freedom of 
movement  and 
activities  
Feel serene, have peace of 
mind 
Have a fulfilling intimate life 
To be cured quickly 
 
This grid will be administered to the enrolled patients after signature of the informed consent. 
The patient will be requested to identify what would be his/her main treatment objective. 
Only one item from the list will be picked by the patient. The investigator must not influence 
the patient into choosing a specific component to the table. The patient will have a grid with 
12 proposals in front of him/her and will not be aware of the dimensions to which the 
proposals relate. The four dimensions typically described in chronic diseases will be considered 
only for analysis, but not submitted to patients. The patient will be given some space and time 
to choose the component without any help or supervision from the investigator. This is 
requested in order to avoid social desirability, defined as the tendency of some respondents 
to report an answer in a way they deem to be more socially acceptable than would be their 
"true" answer. The patient will then conceal his/her response in a provided envelope without 
revealing the chosen component to the physician. 
In the meantime, the treating physician will identify the therapeutic objective that is 
supposedly the most important for his patient, based on his/her discussion with him. The 
physician-reported component will be concealed in a separate envelope and compared with 
the patient-chosen component during the analysis of the secondary endpoints. 
As the primary endpoint of the study, the level of achievement of this therapeutic goal at 3 
months (12/16 weeks) will be assessed by a 4-points Likert scale (Very Unsatisfied; Unsatisfied; 
Satisfied; Very Satisfied), and compared to the DLQI scoring classes. 
 Dermatology Quality of Life Index (DLQI) 
The DLQI is designed to measure the health-related quality of life of adult patients suffering 
from a skin disease. It can be administered in patients aged 16 years and over and takes only 
few minutes to complete. The DLQI consists of 10 questions concerning patients' perception 
of the impact of skin diseases on different aspects of their health-related quality of life over 
the last week. It is not specific to psoriasis and is the most frequently used patient reported 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 23 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
outcome measure in randomised controlled trials in dermatology in general and in psoriasis 
more specifically (Cardiff University, 2019; Puig et al., 2017). 
The DLQI is composed of ten questions grouped in 6 domains “symptoms and feelings”, “daily 
activities”, “leisure”, “work/school”, “personal relationships” and “treatment”. To each 
question the patient will have the followings choices: “Very much”, “A lot”, “A little”, “Not at 
all” or “not relevant” 
Each answer is graded from 0 (“not relevant”, “not at all” or not answered) to 3 (“very much”). 
The DLQI is calculated by adding the score of each question, resulting in a maximum of 30 and 
a minimum of 0. The higher the score, the more quality of life is impaired. A score higher than 
10 indicates that the patient's life is being severely affected by their skin disease (Finlay and 
Khan, 1994). 
More specifically, the total score will be divided into the following subcategories: 
 
0-1 = no effect at all on patient’s life; 
 
2-5 = small effect on patient’s life; 
 
6-10 = moderate effect on patient’s life; 
 
11-20 = very large effect on patient’s life; 
 
21-30 = extremely large effect on patient’s life. 
 Limitation of bias 
In order to limit bias, the sensitivity and specificity analysis need to be performed on a 
population as homogenous as possible. To this end, only patients treated with brodalumab 
(Kyntheum®) will be enrolled. By doing so we will limit the bias due to different treatment 
profiles (schedule of drug administration….). However, Kyntheum® efficacy will not be 
assessed during the study. 
 Study Schedule 
The enrolment period is expected to be 5 months. After the patient’s individual 
treatment plan has been decided, he/she will be approached for informed consent to 
participate in the study and deliver data to use for national and pooled analysis. 
Investigators are expected to enter data into the site specific part of the CRF at baseline and 
at any patient contact throughout the duration of the study. In order to complete and sign-off 
the CRF, a medical record may be used as source for historical data. 
Visits will be according to local clinical practice and not decided in advance by the study 
protocol.  

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 24 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Relevant data from every visit within 52 weeks after baseline will be collected. 
For analysis the following applies: 
Visits that falls within week 12/-16 weeks are proxy for visit at 3 months. If more than one visit 
within this period, the visit closest to week 16 will be used for analysis. 
Visits that falls within week 48-56 weeks are proxy for visit at 12 months (52 weeks ± 4) .If 
more than one visit within this period, the visit closest to week 52 will be used for analysis. 
The study design is the following: 
 
 
The study will enrol consecutive patients planned to receive Kyntheum® and fulfilling the 
eligibility criteria. The assignment of the patient to Kyntheum® must not be decided in advance 
by the trial protocol, but must fall within current practice, and the prescription shall be clearly 
separated from the decision to include the patient in the study. The visit schedule is defined 
by the standard of care as there is no extra mandatory visits related to the participation in the 
study. Patients must be informed about the study and asked for consent to use their data, and 
patients willing to participate be enrolled. 
 
Definition of a non-interventional study 
The study is a ‘non-interventional study’ as defined for drug studies in Directive 2001/20/EC 
(European Commission, 2001) with primary data collection and will follow the guidelines for 
Good Pharmacoepidemiology Practices (Public Policy Committee, 2016). 
This means that: 
 The medicinal product is prescribed in the usual manner in accordance with the terms 
of the marketing authorisation;  
 The assignment of the patient to a particular therapeutic strategy is not decided in 
advance by a trial protocol but falls within current practice and the prescription of the 
medicine is clearly separated from the decision to include the patient in the study  

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 25 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 No additional diagnostic or monitoring procedures are applied to the patients. 
Interviews, questionnaires, blood samples and patient follow-up may be performed as 
part of normal clinical practice. 
 Epidemiological methods are used for the analysis of collected data. 
  Setting 
The study is planned to be conducted in approximatively 25 sites in 2 countries. Investigators 
will be clinical dermatologists. Each participating site is expected to include in average 5/6 
patients. In case of slow recruitment in some sites, the other sites will be allowed to enrol up 
to 10 patients. Inclusion requires that Kyntheum® is prescribed in accordance with the 
approved terms of the marketing authorization in the country and that none of the stated 
contraindications apply. 
Caution should be taken by the treating physician concerning any precautions, warnings and 
potential drug interactions stated in the product label. 
Patients should be included in the study only once. 
The study aims to involve sites and investigators that are representative for HCPs that prescribe 
biologics to patients suffering from psoriasis vulgaris. Sites can be hospital (university, private, 
public) dermatology departments, private dermatology clinics, and all sorts of general 
practices. Sites where patients are prescribed Kyntheum®, but for continuation of care are 
routinely referred to a different site without access to prescribe Kyntheum®, should not be 
selected for this study. 
Information about the PSO-TARGET study should be given after the decision is made to 
treat the patient with Kyntheum®. It will be emphasized that the participation study will not 
condition the patient treatment and will not alter the visit schedule defined by the standard 
of care (3 and 12 months). After enrolment (i.e. signature of the Informed Consent Form), the 
physician will provide the patient with the QoL component grid along with the DLQI 
questionnaire. After having explained the purpose of the table in regards to the study, the 
physician shall give the patient enough time to reflect on which component is the most 
important for him/her without influencing him/her. Both questionnaires will be answered 
after this reflection period. 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 26 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
  Variables 
The following data will be collected from the patients’ medical records and reported on the 
CRF by the investigator. 
 
Consent 
 Unique Study subject number (ISO three letter Country Code, followed by site number 
within country and consecutive patient number within site) 
 Date of Informed Consent (dd.MMM.yyyy) 
 Date of first case report recording (dd.MMM.yyyy) 
 
Demographics 
 Month/Year of Birth (MMM.yyyy) 
 Gender (Male/Female) 
 Weight (kg) 
 Height (cm) 
 
Medical History 
 Date of diagnosis of psoriasis (dd.MMM.yyyy)  
 Location of Psoriasis (List: scalp, nail, body, joint involvement, genital or intimate 
psoriasis, other)  
 Body Surface Area (xx%) 
 Commonly associated comorbidities (List: cardiovascular diseases, diabetes, 
hypertension, depression, psoriasis arthritis, inflammatory bowel disease, other) 
 Smoking habits (never, active with pack years, not active with pack years and years 
since stopped) 
 Alcohol consumption (never, occasionally or regularly with number of days/week, 
number of drinks per day when alcohol is used)  
 Prior psoriasis treatment and posology + reason for discontinuation of the last therapy 
administered  
 Standard occupational category. 
 
 
Psoriasis treatments during study period 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 27 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 Study treatment & co-medications (product name, formulation, dose, number of 
prescribed packages, package size)  
 Date of treatment initiation 
 Date of discontinuation (dd.MMM.yyyy) 
 Reason for discontinuation (noncompliance,  adverse event, requirement for 
alternative therapy, death, pregnancy, other) 
 
Severity/effectiveness 
 Psoriasis area and severity index (PASI) 
 
Patient Reported Outcome 
 Dermatology Life Quality Index (DLQI) score 
 PSO-TARGET QoL component grid 
 
The collected data are presented in the following flow chart of the study : 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 28 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 
  Data Source 
Investigator will complete the CRF with assessments and information according to the 
protocol. In addition, participants (patients) will be asked to enter data about their psoriasis 
symptoms and their Quality of Life, during the data collection period.  
 
The below described scores will be mandatory: 
 
Psoriasis Area and Severity Index (PASI) is the most widely used tool for the measurement of 
severity of psoriasis in clinical research. PASI combines the assessment of the severity 
of lesions and the area affected into a single absolute score in the range 0 (no disease) to 72 
(maximal disease).  
 
Reporter 
Data to be collected 
Base-line 
Visit (Day 0) 
3 months Visit 
(week 12-16) 
12 months visit 
(week 48-56) 
Investigator 
Unique Study subject  
Month/Year of Birth  
Gender  
Weight  
Height  
Date of diagnosis  
Location of Psoriasis  
Body Surface Area  
Commonly associated comorbidities  
Smoking habits 
Alcohol consumption 
Prior psoriasis treatment  
Psoriasis treatment during study period 
Date of discontinuation of psoriasis treatment during study 
period 
Reason for discontinuation of psoriasis treatment during study 
period  
PASI 
QoL component grid 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
 
X 
 
X 
X 
 
Patient 
DLQI 
PSO-TARGET QoL component grid 
X 
X 
X 
X 
X 
X 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 29 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
The Dermatology Quality of Life Index (DLQI) is well recognized Quality of Life questionnaire 
in psoriasis and capture a combination of symptoms, impact on daily routines, and feeling of 
stigmatization. It is a simple 10-question validated questionnaire that has been used in over 
40 different skin conditions in over 80 countries and is available in over 90 languages. Its use 
has been described in over 1000 publications including many multinational studies. It is 
recommended to provide indirect measure of disease severity and is well used in studies on 
psoriasis and mentioned in the UK-treatment guideline (for details, see section 9.1.3). 
 
The PSO-TARGET QoL component grid is a novel tool designed using a retrospective survey 
based on the recollection and experience from 3 clinical dermatologists of patient’s 
expectations. It contains 12 therapeutic goals equally distributed into the 4 major 
psychometric components classically used in quality of life studies in patients suffering from 
chronic diseases (Chassany, 2003; Forestier et al., 2019). These four dimensions are: physical, 
subjective, relational/social and therapeutic. It has never been used before since it was 
designed for the PSO-TARGET study. Each patient will be required to pick only one item in the 
grid as his/her main therapeutic goal (see section 9.1.2). Treatment satisfaction in regards to 
the chosen component will be assessed at 12/16 weeks and 52 weeks by a 4 points Likert Scale 
and the level of concordance will be compared to DLQI scoring classes (described in section 
9.1.2). 
  Study Size 
The main criterion is the sensitivity of the PSO-TARGET tool (percentage of patients who 
consider their target objective as being achieved after 12/16 weeks of treatment as defined 
by a “satisfied or very satisfied” response, assessed on a 4 points Likert scale, among patients 
with a DLQI total score of 0 or 1). 
The sample size calculation is based on the following hypotheses: 
Sensitivity: 90%  
Absolute precision : 10% 
Type I error : 5% 
Power at 80%  
Prevalence: 80% (estimated rate of patient with a DLQI 0-1 after 12 weeks of treatment) 
Hypothesis : 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 30 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
H0 : Se = Se0 
H1 : Se = Se1 > Se0 
With Se=sensitivity, Se0=0.8 and Se1=0.9 
Using the binomial probability formula, the sample size necessary to meet both a significance 
level and a power requirement may be found by solving the following two equations 
simultaneously : 
Significance level B ( s1 > s α | n1, Se0) = α 
B (s1 > s α | n1, Se1) = 1 - β 
Where n1 : patients with a DLQI 0-1, s1 : patients with a DLQI 0-1 and a positive test outcome 
With α=0.05 and 1 - β=0.8 
To obtain n, n1 is inflated by the prevalence P (rate of patients with a DLQI 0-1 = 80%), to 
obtain n = n1 / P 
The software used is PASS version 12, using the Li and Fine method (Li and Fine, 2004). 
Based on these hypotheses, the sample size needed is estimated at 134 evaluable patients. 
Assuming 10% of patients will not be evaluable on main criterion, 150 patients have to be 
included. 
 
 Data Management 
The Study Site will receive data collection tools (CRFs, questionnaires) from CLINACT. 
Whenever possible, complete data sets should be entered. Text field entries and any data 
collected on paper should be legible and follow the requested language standard. 
The Study Site Responsible must sign off the complete data set reported by the site for each 
patient, confirming the collected data. Adverse Event and Other experiences reported 
according to section 11 should be signed off separately by a physician involved in the study. A 
causality evaluation should always be provided.  
Data Management will be carried out according to a Data Management Plan which will be 
written and approved before the design of the study database is finalized. The data 
management provider should approve all data formats before the data collection tools are 
made available to the sites.  
If the written informed consent of a patient is known not to be available in spite of it being 
required, data for this patient is not entered into or is deleted from the database.  

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 31 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
If a patient is erroneously included in the study more than once only the data relating to the 
first inclusion will be kept in the database and be available for analysis. Data from later 
inclusions will be transferred to the first dataset when relevant, i.e. if collected within the time 
frame of the first follow-up period. 
If a patient is included in the study in spite of not being treated according to the approved 
terms of the marketing authorization, data is kept in the database and analysed separately and 
as part of the overall analyses as described in the Statistical Analysis Plan. 
LEO owns the data collected in the CRF and as PRO. General Data Protection Regulation 
(European Commission, 2016) (GDPR) must be adhered to, in addition to any local laws and 
regulations regarding data privacy. The study must follow the EFPIA HCP Code Article 15 Non-
Interventional Studies of Marketed Medicines (The European Federation of Pharmaceutical 
Industries and Associations, 2008). 
The Study Master File compiled by the CRO should be transferred to LEO affiliate when 
complete. The Complete Study Master File comprises both LEO and CRO compiled documents 
but should not hold duplicates. 
The Study Database compiled by CRO should be transferred to LEO HQ when complete.  
Safety data collection and reporting from this NIS must follow the current version of the EMA 
Guideline on Good pharmacovigilance practices (GVP) Module VI – Management and 
reporting of adverse reactions to medicinal products (European Medicines Agency, 2017). For 
reporting please refer to Section 11.  
 
The data extracted from medical records and databases is not owned by LEO. The collection 
must be guided by relevant guidance documents, e.g. Guidance for Industry and FDA Staff: 
Best Practices for Conducting and Reporting Pharmacoepidemiologic Safety Studies Using 
Electronic Healthcare Data (Food and Drug Administration, 2013), the ISPOR Good Research. 
Practice for Retrospective Database Analysis Task Force Report (Berger et al., 2009), and the 
European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) 
Guide on Methodological Standards in Pharmacoepidemiology and Code of Conduct 
(European Medicines Agency, 2010). 
When collecting database data, collection and submission of single case safety data is not 
required. For data collected from medical records, please refer to Section 11. 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 32 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 Data Analysis 
This study is observational and epidemiological methods will be employed for data analyses. 
Descriptive analysis will be performed of all collected data, except data collected only for the 
purpose of data cleaning. 
Section 9.7.1 describes the statistical analyses as foreseen at the time of planning the study. 
Any known deviations from the planned analyses, the reason for such deviations and all 
alternative/additional statistical analyses that may be performed as well as the final statistical 
analysis must be described in a revised Statistical Analysis Plan (SAP) before completion of data 
collection. All later deviations and/or alterations will be summarised in the Clinical Study 
Report. 
 Statistical Analysis Plan 
Data analyses will be performed using SAS Version 9.4 or further (SAS Institute, Cary, NC USA 
software). 
Quantitative parameters will be described using the following summary descriptive statistics: 
number of non-missing values, mean, standard deviation, median, first and third quartiles, and 
minimum and maximum values. 
Qualitative parameters will be described overall using frequencies and percentages. 
Percentages will be calculated on the number of non-missing observations. 
The level of significance for all comparisons is set at 0.05 using two-tailed tests. Confidence 
intervals at 95% could be provided, if relevant. 
 
Description of the population 
The safety population will comprise all included patients having received at least one dose of 
treatment. 
The efficacy population will comprise all included patients who fulfill all inclusion and exclusion 
criteria. 
The total number of patients included in the study, in each analysis population and related 
reasons of exclusion will be described. 
The total number of patients attended each visit, number and reasons of study discontinuation 
will also be described. 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 33 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 
Baseline characteristics 
Baseline and demographic characteristics will be described on the analysis population and will 
be summarized using appropriate summary statistics such as mean, standard deviation, 
median, minimum and maximum for continuous variables, and frequency counts and 
percentages for categorical variables. 
 
 Sensitivity/sensibility analysis 
 Analysis of the primary endpoint 
The primary endpoint will be the evaluation at week 12/16 of the sensitivity and the specificity, 
compared to the DLQI as a standard, of the PSO-TARGET QoL component grid to assess the 
level of satisfaction of patient achieving the therapeutic goal, identified by himself. 
The therapeutic objective will be considered as achieved if the patient gives the responses 
“Satisfied” or “Very Satisfied” on the Likert scale. The response will then be compared to the 
DLQI score at 12/16 weeks. 
It will be described on the efficacy population. 
A contingency table will be constructed as follows: 
PSO-TARGET \ DLQI 
0-1 
2-5 
6-10 
11-20 
21-30 
Very satisfied 
TP 
FP 
FP 
FP 
FP 
Satisfied 
TP 
FP 
FP 
FP 
FP 
Unsatisfied 
FN 
TN 
TN 
TN 
TN 
Very unsatisfied 
FN 
TN 
TN 
TN 
TN 
 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 34 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
This table can be summarized as : 
PSO-TARGET \ DLQI 
0-1 
≥ 2 
Very satisfied ou 
Satisfied 
TP 
FP 
Unsatisfied 
ou Very unsatisfied 
FN 
TN 
TP: True positive 
FP: False Positive 
FN: False Negative 
TN: True Negative 
 
The validity of the QoL component grid will then be assessed by calculating the following 
parameters: 
 Sensitivity: defined as the probability to have patients who have reached their therapeutic 
target (who have responded « satisfied » or « very satisfied » on the Likert scale, globally and 
in each major domains) among patients with a DLQI score between 0 and 1. 
In other terms the sensitivity is defined as the concordance of the QoL component grid and 
the DLQI for the patients with optimal quality of life. 
The sensitivity is calculated by: 
𝑆𝑒=
𝑇𝑃
𝑇𝑃+ 𝐹𝑁 
 
Specificity: defined as the probability to have patients who have not reached their therapeutic 
target (who have responded « unsatisfied » or « very unsatisfied » on the Likert scale, globally 
and in each major domains) among patients with a DLQI score ≥2. 
In other terms the specificity is defined as the concordance of the QoL component grid and 
the DLQI for the patients with suboptimal quality of life. 
The specificity is calculated by: 
𝑆𝑝=
𝑇𝑁
𝐹𝑃+ 𝑇𝑁 
 
The QoL component grid will be validated if these two parameters reach the threshold of 85%. 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 35 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Objective 
Statistical analysis 
Exposure measure 
Outcome measure 
Covariables 
1 
Contingency table; 
Sensitivity / 
Specificity 
N/A 
Concordance level 
between PSO-
TARGET Component 
grid and DLQI at 
12/16 weeks 
N/A 
 
 Analysis of the secondary performance endpoints 
Analyses of secondary endpoints will be performed on the efficacy population.  
No replacement of missing data will be performed. 
The same analysis as the primary performance analysis will be performed at 52 weeks. 
 
 
Efficacy analysis 
- 
 Secondary objective/endpoint : achievement of target objective at 12 weeks, per 
component 
Evaluation at week 12/16 of the level of achievement of the main treatment goal identified by 
the patient in the table at baseline. This evaluation will be performed using a Likert scale in 4 
points (“very satisfied”, “satisfied”, “unsatisfied”, “very unsatisfied”).  
The achievement of the main treatment goal will be defined as a “satisfied or very satisfied” 
response. 
It will be described on the efficacy population. 
- 
The proportion of patients with achievement of the main treatment goal will be described 
and the confidence interval at 95% will be provided. 
- 
The primary analysis will be performed with considering missing data as non responder, 
and a sensitivity analysis will be performed on patients without missing data (observed 
case). 
- 
Search for predictive factors of efficacy. 
The predictive factors of the achievement of the main treatment goal on completed patients 
will be searched among baseline characteristics using binary logistic regressions models. 
Univariate analyses will be used to select (p-value  0.20) the explanatory variables to include 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 36 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
in the multivariate model. The results of univariate and multivariate analyses will be 
interpreted in terms of odds-ratios with their 95% confidence intervals 
In case of correlated variables, only the more significant in univariate will be include in the 
multivariate model. 
Variables with a rate of missing data ≥ 20%, or those with empty categories or with very small 
number will not be considered eligible for this research of predictive factors. 
As part of one of the secondary objectives, the analyses performed for the efficacy endpoint 
are summarized in the table below : 
Objective 
Statistical analysis 
Exposure measure 
Outcome measure 
Covariables 
2.a 
Proportions 
N/A 
Achievement of the 
main goal (yes /no) at 
12/16 weeks 
N/A 
2.b 
Proportions – 
sensitivity analysis 
N/A 
Achievement of the 
main goal (yes /no) at 
12/16 weeks 
 
N/A 
2.c 
Binary logistic 
regression models, 
N/A 
Achievement of the 
main goal (yes /no) at 
12/16 weeks 
Relevant 
confounders (eg : 
demographic data, 
medical history, 
previous treatment…) 
2.d 
Proportions 
N/A 
Achievement of the 
main goal (yes /no) at 
12/16 weeks for each 
component 
N/A 
 
 
Other secondary analyses 
- 
Description and evolution of PASI 
The PASI score will be described at baseline, W12/16 and W52. 
The change in the PASI score between baseline and W12/16 then between baseline and W52 
will be described by summary descriptive statistics, including 95% confidence interval of the 
mean. 
- 
Evolution of DLQI 
The change in the DLQI score between baseline and W12/16 then between baseline and W52 
will be described by summary descriptive statistics, including 95% confidence interval of the 
mean. 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 37 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
- 
Level of agreement between the dimensions reported by the patient and by the treating 
physician. 
The proportion of concordant / discordant choices between the dimensions selected at 
baseline by patient and the physician will be described. 
The level of agreement could be evaluated with a Kappa coefficient. Results will be provided 
in both a quantitative and a qualitative way using the following classes : <0 =« no agreement », 
[0 ; 0.20]=« slight agreement », ]0.20 ; 0.40]=« fair agreement », ]0.40 ; 0.60]=« moderate 
agreement », ]0.60 ; 0.80]=« substantial agreement » et ]0.80 ; 1]=« almost perfect 
agreement ». 
- 
Maintenance of target objective at W52 
The Maintenance of the main treatment goal will be defined as a “satisfied or very satisfied” 
response at W52 for patients who have achieved their initial treatment goal at W12/16. 
The proportion of patients with maintenance of their main treatment goal at W52 will be 
described. 
- 
Change of therapeutic objective at the 1st follow-p visit (W12/16). 
The proportion of patients who changed their main treatment goal at W12/16 will be 
described. 
- 
Level of accordance between PASI ≥ 90 and the satisfaction level in regard to the 
therapeutic objective set by the PSO-TARGET QoL Component grid. 
- 
The change in the PASI scorebetween baseline and the 1st follow-up visit (W 12/16) will be 
described according to the level of achievement of the main treatment goal (achieved or 
not). The percentages of patients with a PASI ≥ 90 that responded “satisfied or very 
satisfied” on the Likert scale at 12 weeks will be calculated and will be compared to the 
percentages of patients with a PASI≥90 that responded “unsatisfied or very unsatisfied”, 
using a khi2 analysis. In case the populations are too small, a Fisher exact test will be used. 
The analyses performed for the secondary endpoints are summarized in the table below : 
Objective 
Statistical analysis 
Exposure measure 
Outcome measure 
Covariables 
1 
Contingency table; 
Sensitivity / 
Specificity 
N/A 
Concordance level 
between PSO-
TARGET Component 
grid and DLQI at 
12/16 weeks 
N/A 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 38 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Objective 
Statistical analysis 
Exposure measure 
Outcome measure 
Covariables 
2.a 
Proportions 
N/A 
Achievement of the 
main goal (yes /no) at 
12/16 weeks 
N/A 
2.b 
Proportions – 
sensitivity analysis 
N/A 
Achievement of the 
main goal (yes /no) at 
12/16 weeks 
 
N/A 
2.c 
Binary logistic 
regression models, 
N/A 
Achievement of the 
main goal (yes /no) at 
12/16 weeks 
Relevant 
confounders (eg : 
demographic data, 
medical history, 
previous treatment…) 
2.d 
Proportions 
N/A 
Achievement of the 
main goal (yes /no) at 
12/16 weeks for each 
component 
N/A 
3.a 
Means 
N/A 
Description and 
evolution of PASI 
score at 12/16 then 
52 ± 4 weeks 
N/A 
3.b 
Mixed effect model 
with repeated 
measurement 
N/A 
Evolution of PASI 
score over the 52 ± 4 
weeks 
PASI score at baseline 
3.c 
Means 
N/A 
Description and 
evolution of DLQI 
score at 12/16 then 
52 ± 4 weeks 
N/A 
3.d 
Mixed effect model 
with repeated 
measurement 
N/A 
Evolution of DLQI 
score over the 52 ± 4  
weeks 
DLQI score at 
baseline 
3.e 
Proportions. 
Khi-Square analysis 
N/A 
PASI≥90 versus 
satisfaction level 
(QoL Component 
grid) 
 
4.a 
Proportions 
N/A 
Proportion of 
concordant choices 
(yes /no) 
N/A 
4.b 
Kappa coefficient 
N/A 
Agreement for the 
selected dimension 
between patient and 
physician 
N/A 
5.a 
Proportions 
N/A 
Maintenance of the 
main goal (yes /no) at 
52 ± 4  weeks  
N/A 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 39 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Objective 
Statistical analysis 
Exposure measure 
Outcome measure 
Covariables 
6.a 
Proportions 
N/A 
Change of the 
therapeutic objective 
(yes /no) at 12/16 
weeks  
N/A 
 
 
Safety analysis 
Study AEs will be tabulated in the final report. AEs will be classified by system organ class 
(SOC), preferred terms (PT) in accordance with the current version of the Medical dictionary 
for Regulatory Activities (MedDRA), causality and seriousness. 
Safety analyses will be performed on the Safety population. 
  Quality Control 
LEO Pharma and/or its designee will monitor study data to ensure data quality and 
conformance to Good Clinical Practices (GCPs). Verification of Case Report Form (CRF) data to 
source documentation, assessment of study progress and assessment of Investigator 
compliance to study protocol and Ethics Committee/IRB requirements will be performed 
according to a pre-defined monitoring plan. 
 
Data Collection 
Data will be collected on printed CRFs by the investigators. The completed CRFs as well as the 
completed questionnaires will be sent to the CRO and entered by a data manager into a 
computer database developed specifically for this study. 
Data will remain anonymous. 
Access to the database will be restricted to personnel responsible for data entry and to data 
management and statistics personnel who are directly involved in the management or analysis 
of this study. Investigators will not have access to the computer database. 
 
Data monitoring 
The Monitoring Plan is a separate document, in which detailed monitoring arrangements such 
monitoring frequency, timing of monitoring visit, access to source data etc. are defined. 
The level of source data verification will be set in the Monitoring Plan. 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 40 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
The Clinical Research Associate (CRA) will always refer to the currently valid version of the 
Monitoring Plan. Monitoring will be performed by outsource consultant according to validated 
procedures as detailed in the Monitoring Plan. 
 
Data validation 
All data management activities will be described in the Data Management Plan. 
During the study, data queries will be generated for data items that are potentially erroneous 
and require appropriate clarification or correction. Prior to database lock, statistical 
verification of the data will be undertaken in order to further assure data quality. 
Over the course of the study, the investigator and the members of the investigator's team 
agree to be available during regular Quality Control visits by the Clinical Research Associate. 
During these visits, the following points will be reviewed: 
- 
Signed informed consent; 
- 
quality of the data collected in the CRFs: accuracy, missing data, consistency of 
the data with the ‘source’ documents (medical files, appointment books, original copies of 
laboratory results, etc.). 
 
 Limitations of Research Methods 
The complementary value of observational studies relies on their robustness for extrapolation 
to the background environment that they aim to represent. Thus, the study population shall 
be representative which means minimization of site selection bias and patient selection bias. 
In studies of patient treatments, the treatment must be representative, meaning the existence 
of the study should not impact prescription habits. 
However in the current study we are observing Kyntheum® users, the estimates will be 
affected by selection bias, e.g. Confounding by indication and channelling bias. Those patients 
the dermatologist chooses to treat with Kyntheum® in the first time after launch, are likely to 
be the most severe patients who have failed on other treatments available (bias by indication) 
and those patients that are “channelized” to the study sites and further chosen as study 
subjects might differ systematically from that group of patients we are trying to describe 
(channelling bias). The influence of channelling bias is tried minimized by consecutive 
enrolment, ensuring that patients are not chosen by the investigator to participate in the 
study. Additionally we expect selection bias due to informed consent, confounding by missing 
data and attrition depending on disease severity.  

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 41 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Acknowledging that the study is prone to many sources of bias and confounding, the design 
of this study has been optimized to reflect the patient journeys to the extent possible. 
 
 Other Aspects 
Audits and Inspections 
The Quality Assurance (QA) unit at LEO may audit the study to ensure that study procedures 
comply with the protocol and LEO standard operating procedures, and that collected data is 
correct and complete. 
Representatives from /IEC or Competent Authority may wish to inspect the study on site. Upon 
receiving notification of such inspection, the Study Site Responsible must immediately contact 
LEO and must make the records available as requested.  
 
Archiving of Study Data and Documentation 
During the course of the study the Site Responsible must as a minimum file the essential 
documents (Section 3), the protocol (all used versions), the list of participating patients, the 
written informed consents, the CRFs and the progress reports in the Study Site File. After final 
database lock the Site Responsible must as a minimum store the list of participating patients 
and the signed Informed Consent Forms on site for at least 5 years or according to local 
regulations (if a longer archiving period is required). The Site Responsible should store 
additional study documentation for a longer period of time as required by any local 
regulations and/or hospital/clinic requirement. 
LEO shall maintain the data and the documentation relating to the study for at least 5 years 
after the studied product is no longer on the market in any country. 
 
10 
Protection of human subjects 
This study is a non-interventional study where the existence of the study has no impact on the 
patient. The treatment of the participating patients will not be any different from patients not 
participating in the study, except for collection of informed consent to use of the patient’s 
data. Informed consent from the patients shall be collected in order to allow collection of non-
standard data such as the psychosocial component and for data monitoring purposes. 
The Site Study Responsible must give the patient (and if applicable, legal guardian) oral and 
written information about the study in a form that the patient (or legal guardian) can 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 42 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
understand, and obtain the patient’s (and if applicable, the patient’s assent and the legal 
guardian’s) written consent before collection by LEO of identifiable patient information 
(hereinafter referred to as personal data). The patient (or legal guardian) must agree that 
his/her data will be processed, stored and may be transferred to third parties, e.g. other 
companies or authorities, that may be located in other countries with potentially different 
regulations for data. Additionally the patient (or legal guardian) must agree that his/her data 
will be transferred to LEO HQ and used for multinational analysis. Before consenting, the 
patient (and if applicable, legal guardian) must be given sufficient time to consider and to pose 
questions. Since the study is observational, the consent only concerns the data collection per 
se and is not consent to any interventional procedure or treatment.  
The patient or legal guardian, if applicable, has the right to withdraw his/her consent at any 
time without prejudice. In the Informed Consent Form it is stated that if consent is withdrawn, 
any data collected before withdrawal of consent will be kept. The original, signed Informed 
Consent Forms must be kept on the Site.  
Data erroneously collected from patients for which written consent is not available, will not be 
included in or will be deleted from the database, as feasible. 
 
For details, see the Patient Information Sheet and Informed Consent Form. 
This study will be conducted in accordance with the current version of the Declaration of 
Helsinki (World Medical Association, 2013), The European Federation of Pharmaceutical 
Industries and Associations (EFPHIA) HCP Code, Article 15 Non-interventional Studies of 
Marketed Medicines (The European Federation of Pharmaceutical Industries and Associations, 
2008), Good Pharmacoepidemiology Practices (Public Policy Committee, 2016) and any local 
regulations. Special attention will be paid to data privacy protection; General Data Protection 
Regulation (GDPR (European Commission, 2016)), LEO Pharma A/S, Industriparken 55, 
Ballerup will be the data holder.  
LEO/CLINACT will ensure that the protocol and any amendments and the Patient Information 
Sheet/Informed Consent Form, Diary and Questionnaires are submitted to the relevant 
Independent Ethics Committees (IECs) and/or competent authorities and/or other national or 
regional authorities according to local requirements. According to applicable regulations, LEO, 
CLINACT will submit required documents to the IEC, such as: 
 periodic updates on the progress of the study 
 notification of the end-of-study 
 a summary of the study results 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 43 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
LEO will keep a copy of all documents submitted and an updated list of all submission and 
approval dates of all documents submitted to the IEC and/or authorities and will provide the 
Site Responsible with a copy of this list. Copies of the documents will be distributed upon 
request. 
None of the data planned to be collected are expected to have any psychological impact on 
the participants, and the questions posed will be presented in a non-judgmental, objective 
manner so that the impact on the patient’s behaviour and honesty in data reporting is 
minimized. The nature of the collected data will not make it possible to track the patients 
without access to the participant lists and Consent Forms stored at the Study Site. The 
collection of this data is considered ethically justified, based on these precautions and the 
following considerations.  
This study focuses on collecting data on the real-life experience of biologic treated psoriasis 
patients for up to 56 weeks.  
It will be a challenge to keep patients motivated to contribute data to the study long-term, 
but psoriasis patients are generally very willing to share their experience with those lending 
non-judgmental ears to their experience.  
 
The Site Study Responsible must give the patient oral and written information about the study 
in a form that the patient can understand, and obtain the patient’s written consent before 
collection of identifiable patient information (hereinafter referred to as personal data). Before 
consenting, the patient must be given sufficient time to consider and to pose questions. Since 
the study is observational the consent only concerns the data collection per se and is not 
consent to any interventional procedure or treatment. 
The patient must agree that his/her data will be transferred to LEO and processed and stored, 
and shared with other business partners responsible for Kyntheum® in other markets. In 
addition, the patient must agree that authorized representatives from LEO or local authorities 
with inspection rights get access to their consent documentation and medical records for 
quality checks on protocol compliance and the data entries if requested. Written informed 
consent to use of collected data must always be obtained before collection of any personal, 
sensitive data. Data erroneously collected from patients for which written consent is not 
available, will not be included in or will be deleted from the database, as feasible. 
The patient has the right to withdraw his/her consent at any time without prejudice. In the 
Informed Consent Form it is stated that if consent is withdrawn, any data collected before 
withdrawal of consent will be kept. The original, signed Informed Consent Forms must be kept 
on the Site. 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 44 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 
11 
Management and Reporting of Adverse Events and Other 
Experiences 
 Definitions 
Adverse Event 
An adverse event (AE) is any untoward medical occurrence in a patient administered a 
medicinal product and which does not necessarily have to have a causal relationship with this 
treatment. An adverse event can therefore be any unfavourable and unintended sign (e.g. an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product. 
Adverse Drug Reaction 
An Adverse Drug Reaction (ADR) is a response to a medicinal product which is noxious and 
unintended. Response in this context means that a causal relationship between a medicinal 
product and an adverse event is at least a reasonable possibility. ADRs may arise from use of 
the product within or outside the terms of the marketing authorisation or from occupational 
exposure.  
Conditions of use outside the marketing authorisation include off-label use, overdose, misuse, 
abuse and medication errors  
Other Experiences 
Other Experiences (OE) are considered ‘non events’ which describe the circumstances around 
the use of a drug which potentially could cause drug related problems or which could 
potentially give positive knowledge of a drug. These may or may not be associated with 
adverse events.  
These events include but are not limited to: unintended beneficial effects, drug exposure in 
utero, drug exposure via breast milk, drug exposure before and/or during pregnancy, paternal 
drug exposure before and/or during pregnancy, occupational exposure, drug overdose or 
abuse, drug misuse, medication error (including potential and intercepted), off label 
use/unapproved use, lack of efficacy, loss of efficacy, drug and food interaction, any suspicion 
of counterfeit product, and suspected transmission of an infectious agent by a medicinal 
product. 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 45 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Seriousness 
A serious ADR or AE is any ADR or AE which results in death, is life threatening, requires 
inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or 
significant disability or incapacity, or is a congenital anomaly or birth defect. 
Life-threatening in this context refers to a reaction in which the patient was at risk of death a 
the time of the event; it does not refer to an event which hypothetically might have caused 
death if it was more severe. 
Medical and scientific judgement should be exercised in deciding whether other situations 
should be considered serious, such as important medical events that might not be immediately 
life-threatening or result in death or hospitalisation but might jeopardise the patient or might 
require intervention to prevent one of the other outcomes listed above.  
Any suspected transmission of an infectious agent via a medicinal product is considered a 
serious ADR. 
Severity  
Severity is a clinical observation and describes the intensity of the event. 
 Mild: 
 
Transient symptoms, no interference with the patient’s daily activities 
 Moderate: 
Marked symptoms, moderate interference with the patient’s daily activities 
 Severe:  
Considerable interference with the patient’s daily activities. 
Causality 
 Possible:A reasonable temporal relationship between the medicinal product 
administration and the event, and there is no other obvious explanation for the occurrence 
of the event. 
 Not related: There is evidence for (an) alternative explanation(s) for the event (e.g. the 
event is explained by one or more of the following: 
a) the patient’s medical condition, 
b) a concomitant medication for which the event is labelled, or 
c) the event occurred prior to the introduction of the medicinal product). 
 
Physician’s responsibility for reporting of Adverse Drug Reactions, 
Adverse Events and Other Experiences 
Physicians and other healthcare professionals involved in the study should report to LEO any 
AE (including SAEs), OE or pregnancy in patients who are or were treated with Kyntheum® 
within 24 hours of becoming aware of it.  

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 46 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
The provided study specific LEO Adverse Event Form – Marketed Products or in case of 
pregnancies – the Pregnancy Form (Part 1) should be used for the reports and completed 
carefully, including the section on causality. A copy of the completed form must be sent, within 
24 hours, to the Safety Contact Person by email or fax (contact details below). 
Contact details of the Safety Contact Persons: 
In France: 
Isabelle CHAILLET-VAN MIERLO 
Telephone Number: +33 1 30 14 40 25 
Email address: pharmacovigilance.fr@leo-pharma.com 
fax number: +33 1 30 14 46 13 
In Belgium:  
Kristien VANELDEREN 
Telephone Number: +32 (0)3 740 78 68 
Email address: drug.safety.be@leo-pharma.com 
The physician should record a precise medical term for the AE or OE, preferably a diagnosis. 
Please observe that death or surgery are considered as outcome, not as an event, so it is the 
event leading to death or surgery which should be recorded.  
Only one AE or OE should be recorded per form. If no diagnosis is available, the physician 
should record each sign and symptom on a separate form. For each AE or OE the causality, 
severity and outcome must be included. Besides the event/experience description, the LEO 
Study ID, and the subject number in the study should be included.  
Important additional information obtained later, e.g. a report of diagnostic procedures or a 
hospital discharge summary should be incorporated, by the reporter, in a follow-up version of 
the already reported AE report and a new causality assessment should be made. The follow-
up report shall be provided to LEO by the same route as the initial AE report. For non-LEO 
products, the physician should notify local competent authorities or the concerned 
manufacturer/ marketing authorization holder, but not both, of AEs at least possibly related 
to the non-LEO product including a reference to the Study ID or study title.  
LEO may request further information from the physician in order to fully assess the safety 
reports.  
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 47 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
 LEO responsibilities for reporting of safety-related data 
LEO will notify the Competent Authorities of all serious and non-serious ADRs related to LEO 
product(s) according to currently applicable pharmacovigilance guidelines for non-
interventional studies.   
All safety-related data on study patients collected in the study database or reported to LEO 
according to the normal procedure for marketed drugs, e.g. serious and non-serious ADRs, will 
be summarized in the Non-Interventional Study Report. 
12 
Plans for Disseminating and Communicating Study Results 
All efficacy and safety data collected in the study will be summarized in the Non-Interventional 
Study Report 
LEO will prepare a Non-Interventional Study Report based on the results obtained. The Final 
Study Report shall be reviewed and approved by the Coordinating Investigator and be available 
within one year from collection of the last data point. In case the Coordinating Investigator 
changes during study conduct, all investigators will be informed and asked for their consent to 
delegate this responsibility to the new Coordinating Investigator. The sites that have enrolled 
patients in the study will be informed about the results when the report is finalized. Summary 
results will be posted on a publicly accessible database. 
LEO aims to have the results of this study published, and acknowledges the right of the 
participating sites to publish results from this study.  
A primary publication based on all study data and following the STROBE guidelines (von Elm 
et al., 2007) in an international peer reviewed journal is foreseen with the Coordinating 
Investigator as the first or last author, if qualifying as author according to the Vancouver 
guideline/Good Publication Procedures vs3 (Battisti et al., 2015) with details in reference list. 
Any manuscripts for secondary publications or abstracts may not be submitted until after the 
primary publication manuscript has been accepted for publication. Any manuscript or abstract 
must be sent to LEO for commenting at least 30 calendar days prior to submission.  
LEO has the right to use the data and results for regulatory and reimbursement purposes, and 
for internal presentation within the company and to partners. In addition, LEO may use the 
data for analysis of pooled data from various studies. 
 
 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 48 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
13 
References 
Augustin, M., Gajur, A.I., Reich, C., Rustenbach, S.J., and Schaefer, I. (2008). Benefit 
Evaluation in Vitiligo Treatment: Development and Validation of a Patient-Defined Outcome 
Questionnaire. Dermatology 217, 101–106. 
Battisti, W.P., Wager, E., Baltzer, L., Bridges, D., Cairns, A., Carswell, C.I., Citrome, L., Gurr, J.A., 
Mooney, L.A., Moore, B.J., et al. (2015). Good Publication Practice for Communicating 
Company-Sponsored Medical Research: GPP3Good Publication Practice for Company-
Sponsored Research (GPP3). Annals of Internal Medicine 163, 461–464. 
Berger, M.L., Mamdani, M., Atkins, D., and Johnson, M.L. (2009). Good Research Practices for 
Comparative Effectiveness Research: Defining, Reporting and Interpreting Nonrandomized 
Studies of Treatment Effects Using Secondary Data Sources: The ISPOR Good Research 
Practices for Retrospective Database Analysis Task Force Report—Part I. Value in Health 12, 
1044–1052. 
Cardiff University (2019). Dermatology Life Quality Index. 
Chassany, O. (2003). De la maladie chronique à la qualité de vie Méthodes d’évaluation. 
Revue Des Maladies Respiratoires 20, 34–37. 
Daudén, E., Puig, L., Ferrándiz, C., Sánchez-Carazo, J.L., Hernanz-Hermosa, J.M., and the 
Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology (2016). 
Consensus document on the evaluation and treatment of moderate-to-severe psoriasis: 
Psoriasis Group of the Spanish Academy of Dermatology and Venereology. Journal of the 
European Academy of Dermatology and Venereology 30, 1–18. 
von Elm, E., Altman, D.G., Egger, M., Pocock, S.J., Gøtzsche, P.C., and Vandenbroucke, J.P. 
(2007). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 
statement: guidelines for reporting observational studies. The Lancet 370, 1453–1457. 
European Commission (2001). Directive 2001/20/EC of 4 April 2001 on the approximation of 
the laws, regulations and administrative provisions of the Member States relating to the 
implementation of good clinical practice in the conduct of clinical trials on medicinal 
products for human use, 2001. 
European Commission (2016). Regulation6/679 of the European Parliament and the Council 
of the European Union 27 April 2016 on the protection of natural persons with regard to the 
processing of personal data and on the free movement of such data, and repealing Directive 
95/46/EC (General Data Protection Regulation). 
European Medicines Agency (2010). The European Network of Centres for 
Pharmacoepidemiology and Pharmacovigilance (ENCePP) Guide on Methodological 
Standards in Pharmacoepidemiology (Revision 5). 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 49 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
European Medicines Agency (2017). Guideline on good pharmacovigilance practices (GVP) 
Module VI – Collection, management and submission of reports of suspected adverse 
reactions to medicinal products (Rev 2). 
Feuerhahn, J., Blome, C., Radtke, M., and Augustin, M. (2012). Validation of the patient 
benefit index for the assessment of patient-relevant benefit in the treatment of psoriasis. 
Archives of Dermatological Research 304, 433–441. 
Finlay, A.Y., and Khan, G.K. (1994). Dermatology Life Quality Index (DLQI)—a simple practical 
measure for routine clinical use. Clinical and Experimental Dermatology 19, 210–216. 
Food and Drug Administration (2013). Guidance for Industry and FDA Staff. Best Practices for 
Conducting and Reporting Pharmacoepidemiologic Safety Studies Using Electronic 
Healthcare Data. 
Forestier, B., Anthoine, E., Reguiai, Z., Fohrer, C., and Blanchin, M. (2019). A systematic 
review of dimensions evaluating patient experience in chronic illness. Health and Quality of 
Life Outcomes 17, 19–19. 
Gelfand, J.M., Weinstein, R., Porter, S.B., Neimann, A.L., Berlin, J.A., and Margolis, D.J. (2005). 
Prevalence and Treatment of Psoriasis in the United Kingdom: A Population-Based Study. 
Archives of Dermatology 141, 1537–1541. 
Huerta, C., Rivero, E., and Rodríguez, L.A.G. (2007). Incidence and Risk Factors for Psoriasis in 
the General Population. Archives of Dermatology 143, 1559–1565. 
Ippagunta, S.K., Gangwar, R., Finkelstein, D., Vogel, P., Pelletier, S., Gingras, S., Redecke, V., 
and Häcker, H. (2016). Keratinocytes contribute intrinsically to psoriasis upon loss of Tnip1 
function. Proceedings of the National Academy of Sciences of the United States of America 
113, E6162–E6171. 
Kerdel, F., and Zaiac, M. (2015). An evolution in switching therapy for psoriasis patients who 
fail to meet treatment goals. Dermatologic Therapy 28, 390–403. 
van de Kerkhof, P.C.M., Reich, K., Kavanaugh, A., Bachelez, H., Barker, J., Girolomoni, G., 
Langley, R.G., Paul, C.F., Puig, L., and Lebwohl, M.G. (2015). Physician perspectives in the 
management of psoriasis and psoriatic arthritis: results from the population-based 
Multinational Assessment of Psoriasis and Psoriatic Arthritis survey. Journal of the European 
Academy of Dermatology and Venereology : JEADV 29, 2002–2010. 
Krueger, G., Koo, J., Lebwohl, M., Menter, A., Stern, R.S., and Rolstad, T. (2001). The Impact of 
Psoriasis on Quality of Life: Results of a 1998 National Psoriasis Foundation Patient-
Membership Survey. Archives of Dermatology 137, 280–284. 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 50 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
Kurd, S.K., and Gelfand, J.M. (2009). The prevalence of previously diagnosed and 
undiagnosed psoriasis in US adults: results from NHANES 2003-2004. Journal of the American 
Academy of Dermatology 60, 218–224. 
Lebwohl, M. (2018). Psoriasis. Annals of Internal Medicine 168, ITC49–ITC64. 
Lebwohl, M., Strober, B., Menter, A., Gordon, K., Weglowska, J., Puig, L., Papp, K., Spelman, 
L., Toth, D., Kerdel, F., et al. (2015). Phase 3 Studies Comparing Brodalumab with 
Ustekinumab in Psoriasis. N Engl J Med 373, 1318–1328. 
Li, J., and Fine, J. (2004). On sample size for sensitivity and specificity in prospective 
diagnostic accuracy studies. Statistics in Medicine 23, 2537–2550. 
Lowes, M.A., Bowcock, A.M., and Krueger, J.G. (2007). Pathogenesis and therapy of psoriasis. 
Nature 445, 866. 
Public Policy Committee, I.S. of P. (2016). Guidelines for good pharmacoepidemiology 
practice (GPP). Pharmacoepidemiology and Drug Safety 25, 2–10. 
Puig, L., Thom, H., Mollon, P., Tian, H., and Ramakrishna, G.S. (2017). Clear or almost clear 
skin improves the quality of life in patients with moderate-to-severe psoriasis: a systematic 
review and meta-analysis. Journal of the European Academy of Dermatology and 
Venereology 31, 213–220. 
Richard, M.-A., Corgibet, F., Beylot-Barry, M., Barbaud, A., Bodemer, C., Chaussade, V., 
D’Incan, M., Joly, P., Leccia, M.T., Meurant, J.M., et al. (2018). Sex- and age-adjusted 
prevalence estimates of five chronic inflammatory skin diseases in France: results of the 
« OBJECTIFS PEAU » study. Journal of the European Academy of Dermatology and 
Venereology 32, 1967–1971. 
Sampogna, F., Puig, L., Spuls, P., Girolomoni, G., Radtke, M.A., Kirby, B., Brunori, M., 
Bergmans, P., Smirnov, P., Rundle, J., et al. (2017). Prevalence of alexithymia in patients with 
psoriasis and its association with disease burden: a multicentre observational study. British 
Journal of Dermatology 176, 1195–1203. 
Stern, R.S., Nijsten, T., Feldman, S.R., Margolis, D.J., and Rolstad, T. (2004). Psoriasis Is 
Common, Carries a Substantial Burden Even When Not Extensive, and Is Associated with 
Widespread Treatment Dissatisfaction. Journal of Investigative Dermatology Symposium 
Proceedings 9, 136–139. 
The European Federation of Pharmaceutical Industries and Associations (2008). EFPIA HCP 
CODE. EFPIA code on the promotion of prescription-only medicines to, and interactions with, 
healthcare professionals. 

NIS-PSO-TARGET 
Non-Interventional Study Protocol 
Study ID RCB: 2020-A00652-37 
Page 51 of 51 
 
 
 
 
THIS DOCUMENT CONTAINS TRADE SECRETS, AND/OR COMMERCIAL OR FINANCIAL INFORMATION, PRIVILEGED OR CONFIDENTIAL, DELI-
VERED IN CONFIDENCE AND RELIANCE THAT SUCH INFORMATION WILL NOT BE COPIED OR MADE AVAILABLE TO ANY THIRD PARTY 
WITHOUT THE WRITTEN CONSENT OF LEO PHARMA A/S 
 
World Medical Association (2013). World Medical Association Declaration of HelsinkiEthical 
Principles for Medical ResearchInvolving Human Subjects. 
 
Annex 1. PSO-TARGET Component Grid 
Physical 
Subjective 
Relational/ social 
Therapeutic 
Not be 
limited/handicaped by 
the pain 
Think less or not at all about 
the disease  
Spend quality time with family, 
friends or colleagues 
Need to think less about 
treatment and care 
Do not feel any 
functional discomfort 
(itching, rash) in my 
daily activities 
Do not feel any anxiety from 
the disease 
Not caring about what people think 
about me 
Encounter very few, if any, 
drug discomfort  
Have freedom of 
movement  and 
activities  
Feel serene, have peace of 
mind 
Have a fulfilling intimate life 
To be cured quickly