Impact of Clinical and Psychological Factors on Treatment Satisfaction in Psoriatic Patients in Biological Therapy
Conditions: Psoriasis
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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Study protocol 
"Impact of clinical and psychological factors on treatment satisfaction 
in psoriatic patients in biological therapy" 
 
Version: 1.0 of 14/03/2023 
ACRONYM STUDY: PSOSAT 
 
1. Summary of the study 
Psoriasis is an inflammatory disease with a chronic-relapsing course with a significant impact on the 
physical and mental well-being of patients. Fortunately, in recent years, the introduction of 
increasingly selective biological therapies has allowed to obtain an excellent control of the disease, 
with high rates of complete (PASI100) or almost complete (PASI90) remission in treated patients. 
At the same time, however, various studies have shown that the quality of life of these patients and 
satisfaction with these therapies do not always correlate with the high levels of effectiveness of 
these drugs and this often represents a limit, as it has negative feedback on adherence to treatment. 
This study aims to identify, through the use of questionnaires, demographic, clinical and 
psychological factors that could better correlate with the satisfaction of psoriatic patients in 
systemic therapy with biological drugs for more than a year belonging to the Dermatology Clinics of 
the A. Gemelli-IRCCS University Hospital. 
 
 
 
 
 
1. Scientific background 
 
Psoriasis is a chronic inflammatory disease with a significant impact on the quality of life of those 
affected. The introduction of monoclonal antibodies directed against key cytokines in the 
pathogenesis of the disease has so far allowed to obtain excellent results not only in terms of 
objective clinical response (PASI90, PASI100), but also in terms of quality of life (DLQI) thanks to the 
speed of action, the long-term response and the better safety profile compared to so-called 
"traditional" drugs,  such as cyclosporine, methotrexate and acitretin. 
Patient satisfaction is one of the main elements to ensure the success of a systemic therapy for a 
chronic disease such as psoriasis, as it is closely related to adherence to treatment. 

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Although the literature suggests that treatment satisfaction derives mainly from objective data such 
as the extent of residual disease, there are no unequivocal data on which values of the disease 
severity index (PASI) are associated with greater patient satisfaction. Recent studies have also 
shown that a certain percentage of patients who achieve optimal responses with biological 
therapies (PASI90, PASI100, absolute PASI <2), still report an impact of the disease on their quality 
of life (assessed by DLQI) (2021 Life Basel Kirsten et al Which PASI OutcomeIs Most Relevant to the 
Patients in Real-World Care?) This paradox has been partly explained by the localization of residual 
disease in so-called sensitive sites and by the presence of a possible associated symptomatology, 
but it is still partially unexplored how the psychological profile of the patient can influence this 
aspect. (DermatolTher 2022 Lebwol M. et al "Evolution of Patient Perceptions of Psoriatic Disease: 
Results from the Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) 
Survey"). 
In particular, it remains to be clarified the weight of some psychopathological characteristics of 
patients and how these can negatively affect the quality of life and consequently satisfaction with 
treatment. 
On the other hand, it is known that there is an increased prevalence of numerous psychiatric 
pathologies in psoriatic patients: depression, bipolar disorder, anxiety, psychosis, cognitive 
impairment, sexual disorders, sleep disorders, eating behavior and personality disorders. (Rev. 
Neurosci 2018 Amanat M. et al "Neurological and psychiatricdisorders in psoriasis"). 
With regard to personality alterations, several studies have shown an increased prevalence 
(37.4%) of a particular personality profile, Type D, in patients with psoriasis: this is a personality 
profile characterized by negative emotionality, often associated with a higher incidence of 
psychiatric diseases (such as anxiety and depression) and which could affect satisfaction with 
therapies. 
 
 
1. Objectives of the 
study 
 Primary objective 
The primary objective of the study is to evaluate the effect of objectively measurable clinical 
variables such as: 
1. 
age of onset and duration of illness 
2. 
the presence of comorbidities 
3. 
possible combination with other treatments 
4. 
the residual localization of disease 
5. 
the presence/absence of psoriatic arthritis 

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6. 
the residual PASI 
7. 
PASI improvement compared to baseline 
8. 
DLQI 
9. 
DLQI improvement compared to baseline 
10. 
the achievement of an optimal response in terms of: 
1. ABSOLUTE PASI <2 
2. 
 90% and 100% reduction in PASI score from baseline 
3. DLQI between 0-5 
on satisfaction with the treatment of psoriatic patients, who have been on therapy for at least a 
year with a biological drug. Satisfaction will be expressed in terms of the score derived from the 
Treatment Satisfaction Questionnaire for Medication (TSQM-9). 
 
Secondary objective 
 
As a secondary objective, the relationship of specific psychopathological characteristics (Type D 
personality, Depression) with treatment satisfaction will also be evaluated. 
 
Duration design and setting of the study 
 
It is an observational study with monocentric drug. 
 
The study will last 12 months including enrolment and will begin after the ethics committee has 
delivered a favourable opinion. 
It will be conducted at the Institute of Dermatology and Venereology of FPG. 
 
 
 
 
 
 
1. Study population 
 
Patients diagnosed with psoriasis belonging to the Dermatology and Venereology clinics of FPG 
already treated with a systemic biological drug for at least one year will be included. 
 
   Inclusion criteria: 
 
-Patients with age>18 years, of both sexes; 
 
-Diagnosis of plaque psoriasis, with or without concomitant arthritis; 
 

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-Patients who have been receiving systemic biologics for at least one year and have disease severity 
(PASI) and quality of life (DLQI) data available at baseline (prior to initiation of treatment); 
-Signature of the written informed consent; 
 
 Exclusion criteria: 
 
-Presence of a psychiatric pathology already diagnosed 
 
-Patients with psoriasis variants (pustular, guttate, palmoplantar) 
 
1. Tools and Variables 
For each patient, the basic socio-demographic characteristics (age, sex, level of education) and the 
presence of comorbidities, any comedications, age of onset and duration of illness will be recorded. 
The severity of psoriasis at the time of enrollment will also be evaluated: absolute PASI at the time 
of enrollment, possible presence of disease localizations in "special" locations (scalp, nails, genitals, 
palmoplantar), presence or absence of psoriatic arthritis. 
We will also record the characteristics of the ongoing biological treatment: PASI at baseline, 
duration of treatment, molecule, number of systemic therapies previously used, possible 
concomitant therapy with another systemic drug. 
The PASI (Psoriasis Activity and Severity Index) is an index created to assess the severity of psoriatic 
lesions and their extension through the indication of the percentage of body area that presents 
lesions and a definition of the intensity of some local signs such as erythema, infiltration and 
desquamation, psoriasis is considered mild with a PASI <10,  moderate if the PASI is between 10 and 
20 and severe if greater than 20. 
 
Treatment satisfaction will be assessed using the Treatment Satisfaction Questionnaire for 
Medication (TSQMv.II). The TSQM-II is an 11-item questionnaire developed to assess treatment 
satisfaction with any treatment. There are four scales: treatment effectiveness (two elements), side 
effects (three elements), treatment convenience (three elements) and overall satisfaction (two 
elements). Patients rate their experiences with treatment during the last 2-3 weeks between 
"Extremely dissatisfied" and "Extremely satisfied" on five- or seven-point Likert-type scales. Higher 
TSQM-II scores indicate greater satisfaction with treatment. The questionnaire refers to a period of 
2-3 weeks before the time of completion of the questionnaire. 
We will also evaluate the psychological structure of patients and in particular the presence of a 
"Type D Personality" through a special validated questionnaire (DS14) that identifies this type of 
personality in those who obtain scores of "Negative Affectivity" or "Social Inhibition" higher than 

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10. In addition, the PatientHealth Questionnaire-9 (PHQ-9) will assess the possible presence and 
severity of depression by means of a short scale specific to General Practice (Spitzer et al., 1999) 
consisting of two questions. The first investigates the presence "in the last two weeks" of the 9 
symptoms of depression according to the DSM-IV also taken up in the DSM-5. Only this question 
determines the score of the PHQ-9. Each symptom is assessed on a 4-point scale. The second 
question assesses the functional impairment that depression causes on the normal course of the 
patient's life. This question does not count towards the PHQ-9 score. 
The PHQ-9 score ranges from 0 to 27. Scores between 5 and 9indicate the presence of a 
subthreshold depression. The score of 10 is the optimal cut-off to highlight clinically relevant 
depressions (Gilbody et al., 2007) with three different levels of severity depending on the score 
(MacArthur & MacArthur, 2009). 
Finally, the dermatological quality of life will be evaluated through DLQI (Dermatology Life Quality 
Index), a questionnaire of 10 questions that evaluates with a score from 0 to 30 the impact of the 
disease on the patient's quality of life (a score higher than 10 identifies a strongly compromised 
quality of life) 
1. ENDPOINT 
 
Primary ENDPOINT 
 
Effect of objectively measurable clinical variables on satisfaction - assessed by TSQMv.II - towards 
treatment, in a sample of psoriatic patients who have been treated for more than one year with a 
biological drug. This evaluation will be carried out by: 
1. 
the possible localization of the residual disease, measurable through the quantitative 
definition (body surface area-BSA: percentage of skin surface area with disease residue) and  
 
qualitative (PASI) of the disease residue compared to baseline; 
2. 
the improvement of the PASI and DLQI scores compared to the baseline, quantifiable 
through the measurement of the difference between the score at the last clinical 
reassessment (Tlast) and the score at the baseline (T0) (respectively delta PASI and delta 
DLQI); 
3. 
the evaluation of the efficacy of the treatment in terms of i) proportion of patients 
who achieve a reduction of 50%, 75%, 90%, 100% of the PASI score (PASI50, PASI75, PASI90, 
PASI100) compared to baseline, ii) achievement of an absolute PASI <2 at the last clinical 
reassessment (Tlast), iii) proportion of patients achieving a DLQI between 0-5 at the last 
clinical re-evaluation (Tlast); 
effect/association of clinical factors on/with satisfaction at treatment; 

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Secondary ENDPOINT 
The impact of psychopathological characteristics on treatment satisfaction, assessed by TSQMv.II, 
will be carried out through: 
4. 
Evaluation of the psychopathological effect of psoriasis on the patient using 
questionnaires: PatientHealth Questionnaire-9 (PHQ-9) and DS14 
 
1. Safety/adverse event management 
Definitions 
"Adverse event" means any harmful clinical event that occurs in a person who has been given a medicinal 
product and who does not necessarily have a causal relationship with such treatment. 
"Adverse reaction" means the unintended and unintended reaction resulting not only from the authorised use 
of a medicinal product under normal conditions of use but also from medication errors and uses not in 
accordance with the indications given in the marketing authorisation, including misuse and abuse of the 
medicinal product. 
"Serious adverse reaction" means an adverse reaction that causes: 
-death 
- life threatening, 
- hospitalisation or prolongation of hospitalisation, 
- severe or permanent invalidity, 
- congenital anomalies/birth defects, 
- other clinically relevant condition. 
   
Management of adverse events 
All adverse events will be collected, recorded and evaluated by severity and relationship to investigational and 
non-investigational medicinal products for the purpose of identifying suspected adverse reactions. 
 
 
 
Any suspected adverse reaction will be reported to the National Competent Authority - AIFA, regardless of the 
severity, according to the post-marketing pharmacovigilance flow, provided for by DM 30 April 2015 and GVP 
(Good Vigilance Practices) module VI, by communication to the Local Pharmacovigilance Manager for inclusion 
in the National Pharmacovigilance Network and, where required, to the Ethics Committee. 
Suspected adverse drug reactions should be reported to the Local Pharmacovigilance Manager within 48 hours 
of becoming known, and suspected adverse reactions from biological medicinal products should be reported no 
later than 36 hours. 
 
9. Statistical analysis 
 
Sample size 
 
The calculation of the sample size was carried out taking into account the subgroup analysis carried 
out by Schaarschmidt et al (Acta DermVenereol 2015) which evaluated the associations between 

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sociodemographic characteristics, disease severity and duration of the same with treatment 
satisfaction, expressed in terms of TSQM score. In this work a DLQI score between 0-5 is associated 
with a higher average TSQM score. 
Considering a significance level (α) of 0.05 and a potency (1-β) of 0.80, the estimated sample size 
for each of the two subpopulations (patients with DLQI between 0-5 and greater than 5) is 52. 
We therefore estimate to include in our study at least 104 patients with psoriasis who have been 
treated for at least one year with biological drugs. 
 
Statistical analysis 
Categorical variables will be described as absolute frequencies and percentages, while variables 
continuous as mean and standard deviation (±SD) and in the case of non-Gaussian distribution as 
median and interquartile range (IQR). 
Several optimal response endpoints will be considered and compared: absolute PASI <2, 90% and 
100% reduction in PASI score compared to baseline after one year of treatment (PASI 90, PASI 100), 
DLQI improvement >4 points, DLQI achievement between 0-5. 
The ANOVA test (analysis of variance) followed by the Tukey HSD, Bonferroni, Sidak or Scheff tests 
to adjust the p value in the case of multiple comparisons, will be used to perform subgroup analysis 
and satisfaction assessed by TSQM score. You will consider transformations of the TSQM satisfaction 
score to obtain a normal distribution. Subgroup analyses to compare the best treatment ever 
obtained by participants will be performed with the χ2 test or with the exact Fisher test for small 
numbers of participants within the subgroups. 
Multivariate linear regression analysis will be performed to estimate the association between the  
 
TSQM defined as dependent variable and the BSA score (%), residual PASI (both as continuous and 
categorical variable i.e. PASI<2 versus PASI>=2), delta PASI (continuous variable), proportion of 
patients who achieved PASI50, PASI75, PASI90, PASI100, DLQI (both as a continuous and categorical 
variable i.e. DLQI 0-5 versus DLQI>5) and delta DLQI (continuous variable),  possible presence of 
depression (presence / absence and level of severity if present), possible presence of type D 
personality, defined as independent variables, considering sex, age (in years) duration of the disease 
(in years), possible presence of psoriatic arthritis (yes / no), possible presence of disease 
localizations in "special" sites (scalp, nails, genitals, palmoplantar) (yes / no), possible combination 
of the biological drug with a traditional systemic therapy (yes/no) as confusing. 
A standardized regression coefficient β will be calculated for each independent variable, which 
indicates the magnitude of the change in the TSQM as the respective variable changes, keeping the 
others constant. 
In addition, a ROC curve with a logistic regression model will be estimated, inserting the TSQM 
(dichotomous variable of global satisfaction >=75 and <75, Mekies C et al. Patient Preference and 

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Adherence, 2018) as an objective variable and the residual PASI score as an explanatory variable, 
the psychological profile of the patient both in terms of presence/absence of personality D-trait and 
PHQ-9 score as covariates,  to evaluate the cut-off value of the PASI score using the Youden index. 
The unmatched data test will be used to perform bivariate analyses on the effects of sex, age, PASI, 
DLQI, disease duration, psoriatic arthritis on satisfaction assessed by TSQM score. Subgroups will be 
defined according to gender, age (< 50 or ≥ 50 years), PASI (<2 or >=2), DLQI (0-5 or > 5), duration of 
disease (0-10 or > 10 years) and presence or absence of psoriatic arthritis. 
Associations and differences will be considered statistically significant with a p ≤ 0.05.  
All analyses will be performed with the software STATA/BE v.17.0