SEquential Treatment of PSoriasis With Biologics
Conditions: Psoriasis
Sponsor: Royal United Hospitals Bath NHS Foundation Trust

 
 
Date: 28/07/2025 
 
 
 
SEquential Treatment of PSoriasis with Biologics 
STEPS Study 
 
 
Study protocol (Version 5.0) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Date: 28/07/2025 
 
 
 
Introduction 
Psoriasis affects up to 60 million people worldwide (1) and can lead to significant morbidity and a 
decline in quality of life (2, 3). Over the past two decades, rapid advances have been made in the 
understanding and treatment of this condition; multiple novel drugs have been approved (4). In 
the United Kingdom, there are currently 14 biologic and targeted synthetic therapies approved by 
National Institute for Health and Care Excellence (NICE) for use in psoriasis, within the classes 
anti-TNFα (TNFi), anti-interleukin-17 (IL-17i), anti-interleukin-12/23 (IL-12/23i), anti-interleukin-23 
(IL-23i), PDE-4 inhibitors (PDE4i) and TYK2 inhibitors (TYK2i).  
Randomised controlled trials have proven efficacy of biologics in psoriasis. However, in many 
trials, eligibility criteria include limitations on the number and class of prior biologic, for example 
in reSURFACE 1 and 2 evaluating tildrakizumab versus placebo or etanercept for psoriasis, 
exclusion criteria precluded previous use of IL-23i (p40/p19) or IL-17i (5).  Within reported trials 
there are also limited sub-analyses of biologic experienced patients, assessing response stratified 
by number of previous lines of biologic treatment.  
With real-world use, a significant percentage of patients on biologics for psoriasis stop treatment, 
and switch to another biologic, as a result of factors including inefficacy and adverse effects (6). 
Due to the chronicity of psoriasis, this can lead to a patient having multiple lines of treatment over 
time. Drug survival reduces with increasing lines of therapy, with previous biologic treatment 
shown to be a specific effect modifier for the risk of discontinuation associated with effectiveness 
in psoriasis (7). Drug survival is an important measure of real-world use, however is impacted by 
various factors including availability of a medication, patient and physician behavioural factors 
and adverse effects (8), and so is not a perfect substitute for efficacy.   
A recent systematic literature review evaluating effectiveness of biologics beyond first line in 
psoriasis found that currently available evidence is mainly observational, and at high risk of bias 
(9). There was a scarcity of data available beyond second line, with data only available for 260 
patients on 3rd/3rd+ line, and 152 patients on 4th/ 4th+ line. A meta-analysis of PASI75 response 
at 12-16 weeks did not find a serial reduction in response with sequential lines of treatment, 
however interpretation of this result is impeded by the limitations of the available data. 
Further studies are required to gain understanding of response to later lines of biologic treatment 
in psoriasis, to assess if prior treatment has an impact on later efficacy response. The 
development of evidence of effectiveness beyond third line would also help inform healthcare 

 
 
Date: 28/07/2025 
 
 
 
systems that currently ration the permitted number of lines of biologic per patient, and contribute 
to more informed discussions between patients and clinicians when switching biologic treatment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Date: 28/07/2025 
 
 
 
Study Aim 
The aim of the study is to assess clinical response to sequential lines of biologic and targeted 
synthetic treatment in psoriasis.  
 
Hypothesis  
Our hypothesis is that the primary response (at 12-16 weeks) to sequential lines of biologic and 
targeted synthetic treatment in psoriasis does not reduce with increasing lines of treatment after 
2nd line biologic or targeted synthetic treatment.   
 
Objectives 
i. 
To evaluate the proportion of patients achieving a PASI75 response to 3rd + line biologic 
or targeted synthetic therapy compared to 2nd line at 12-16 weeks and 6 months.  
ii. To assess the proportion of patients achieving PASI75, PASI90 and PASI100 to 3rd, 4th, 
5th and 6th + line biologic or targeted synthetic therapy compared to 2nd line, at 12-16 weeks 
and 6 months. 
iii. To evaluate the likelihood of achieving PASI ≤2 to 3rd, 4th, 5th and 6th + line biologic or 
targeted synthetic therapy compared to 2nd line, at 12-16 weeks and 6 months. 
iv. To evaluate the likelihood of achieving PASI75 to 2nd line TNFi, IL17i, IL23i, IL12/23i after;  
a. Primary inefficacy to 1st line TNFi   
b. Secondary inefficacy to 1st line TNFi    
v. To determine whether primary or secondary inefficacy to 1st biologic or targeted synthetic 
therapy influences likelihood of response (PASI75 at 12-16 weeks) to subsequent lines of 
therapy 
 
STUDY DESIGN  
Retrospective observational cohort study 
Inclusion criteria 

 
 
Date: 28/07/2025 
 
 
 
• 
Age ≥18 years  
• 
Diagnosis of chronic plaque psoriasis by a Dermatology consultant 
• 
Prior treatment with biologic or targeted synthetic treatment (1 to 10 lines) for psoriasis in 
the United Kingdom  
Exclusion criteria 
• 
Age <18 years  
• 
Diagnosis of other forms of psoriasis for example generalised pustular psoriasis 
 
Methods 
Data collection 
Dermatology centres from around the United Kingdom who treat psoriasis patients with biologics 
will be recruited. Participating clinicians will be asked to submit data on patients treated with 
biologic and targeted synthetic therapy from a retrospective case note review. An online survey 
will be developed on the platform RedCAP (Research Electronic data Capture), to collect and 
store data. The data will be fully anonymous when inputted and will consist of retrospective 
information obtained during routine clinic appointments, with no additional appointments required 
for this study. Each patient will be given a study ID which will be kept with the corresponding 
patient identifying information at the study site, with no access to identifying information from the 
analysts.   
Demographic data for each patient will be obtained at baseline, including the variables age, sex, 
ethnicity and comorbidities. A dataset of baseline, first follow up and 6-12 month follow up 
outcome measures (Psoriasis Area Severity Index (PASI), patient global assessment (PGA), 
Dermatology Life Quality Index (DLQI)) will be collected for each line of biologic treatment (Table 
1). These measures will be used to calculate the percentage of patients achieving the predefined 
outcomes of interest (PASI75/90/100, PASI ≤2) and to assess for inter-line variability in response. 
In line with NICE guidance, it is likely that the PASI and DLQI will be the most consistently 
recorded data, but other domains of disease activity will be collected where available.   
Table 1 Outcome measures to be assessed 

 
 
Date: 28/07/2025 
 
 
 
Outcome 
measure 
Baseline 
Baseline for 
each line 
First follow up 
(12-16 
weeks) 
for each line 
6-12 
months 
follow up for 
each line  
Age  
x 
 
 
 
Sex 
x 
 
 
 
Ethnicity  
x 
 
 
 
Age at psoriasis 
diagnosis  
x 
 
 
 
Comorbidities 
x 
 
 
 
Diagnosed PsA 
x 
 
 
 
Smoking status 
x 
 
 
 
Height 
x 
 
 
 
Psoriasis type 
Small 
or 
large 
chronic plaque 
x 
 
 
 
Nail  
x 
 
 
 
Scalp 
x 
 
 
 
Palmoplantar  
x 
 
 
 
Genital 
x 
 
 
 
Previous systemic/ 
UV treatments 
x 
 
 
 
Age at first biologic x 
 
 
 
Concurrent 
systemic 
or 
UV 
treatment 
 
x 
 
 
Weight/ BMI 
 
x 
 
x 
PASI 
 
x 
x 
x 
DLQI 
 
x 
x 
x 
BSA % 
 
x 
x 
x 
Physician 
global 
assessment 
 
x 
x 
x 
Patient 
global 
assessment 
 
x 
x 
x 
 
Statistical analysis  
Data analysis will be undertaken using SPSS and R. Demographic data will be analysed 
descriptively. Each patient will submit all treatment courses for analysis, for example, data from a 

 
 
Date: 28/07/2025 
 
 
 
patient treated with 3 lines of biologic or and targeted synthetic medicine will be used in the first-, 
second- and third-line analyses. 
This study aims to evaluate the proportion of patients achieving a relative PASI response 
(PASI75, 90 AND 100) across different lines of biologics. The primary response variable will be 
the binary PASI75 outcome. Explanatory variables include the line of therapy (categorised as 
1st, 2nd-3rd or 4th+ line), baseline PASI, age (categorised into 10-year intervals), disease 
duration (grouped into two-year intervals), sex, BMI and smoking status. 
All statistical analyses will be performed using R. Logistic generalised estimating equations 
(GEEs) will be employed, utilising the R package 'gee' to account for repeated observations 
within individuals. An exchangeable correlation structure will be specified, assuming equal 
correlation among all pairs of observations within a given patient.  
A complete case analysis will be conducted for model fitting, including only patients with 
available data for all explanatory variables at each line of therapy. This approach is valid under 
the assumption that data are missing at random (MAR), which is reasonable in this case given 
that missingness is likely due to differences in clinical practice and data collection systems. 
Patients with missing lines of therapy within their treatment sequence will be included in the 
analysis, as excluding lines beyond a missing entry would reduce the sample size and increase 
variance.  
To assess the likelihood of achieving PASI75/90/100 AND PASI<2 across different lines of 
therapy, crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) will be 
estimated using logistic GEEs. Crude models adjust only for repeated measures, while adjusted 
models account for sex, age, baseline PASI, BMI and smoking status.  
Recruitment approach 
Each centre will submit detailed retrospective data collected as part of standard care on patients 
recruited from routine clinics. We will recommend that data is submitted on the most recent 
patients starting each line of biologic treatment for psoriasis, with 5 consecutive patients for each 
line of therapy (first through maximum) where available. We propose competitive recruitment with 
a maximum of 50 patients per centre until the sample size is met. We will aim to recruit 5-6 centres 
in case of under recruitment of patients.  
Consent 
Individual consent from patients is not required due to the nature of the data according to the 
HRA: this consists of retrospective data collected during standard patient care with no changes 
made to a patient’s standard care. 
Sample size and outcome rationale 

 
 
Date: 28/07/2025 
 
 
 
A meta-analysis of the currently available evidence for effectiveness of biologics at achieving 
PASI75 at 12-16 weeks in different lines of therapy has shown a rate of 61%, 56.1%, 79% and 
61.6% in 1st, 2nd, 3rd/3rd+ and 4th/4th+ lines respectively (Figure 1) (9). The primary question of this 
study is to compare 2nd line biologic response to 3rd+ line. The meta-analysis indicates that the 
likelihood of achieving PASI75 does not reduce with subsequent lines of treatment. The sample 
size is therefore based on a non-inferiority comparison of the proportion of patients achieving 
PASI75 to 2nd line (56.1%) versus 3rd/4th+ lines. At 5% significance, 80% power, assuming a 56% 
PASI75 in both and non-inferiority limit of 10%, a sample size of 305 treatment courses per group 
is required. In additional, 61 treatment courses in first line only will be collected for comparison. 
Therefore, a total sample size of 671 treatment courses will be sought. A treatment course is 
equivalent to one line of a biologic or targeted small molecule treatment in one patient. As all 
treatment courses per participant will be used for analysis, the number of patients required to be 
recruited is smaller than the sample size (Table 2). 
Table 2. Number of recruited patients required to achieve treatment course sample size 
 Line of 
treatment    
No treatment 
courses required 
per group   
Number of patients 
required per line to 
achieve adequate 
treatment courses   
Treatment courses 
total per line if 
number achieved   
Treatment courses 
per group if 
number achieved 
1st   
61  
61  
366  
366 
2nd   
305  
61  
305  
205 
3rd   
305   
61  
244  
610 
4th   
61  
183  
5th   
61  
122  
6th+   
61  
61  
Total   
671  
366  
1281  
 
Data storage, confidentiality and archiving 
All information collected during the study will be kept strictly confidential.  Information will be 
anonymous when inputted into the RedCAP system and will be held securely within the system 
at the University of Bath.  
The study will comply with all aspects of the 1998 Data Protection Act and operationally this will 
include: 

 
 
Date: 28/07/2025 
 
 
 
• 
Each participant is to be allocated an anonymous patient ID; the local sites will hold the 
personal information of the corresponding patient. No personal identifying information will 
be available to the analysis team at any point of the study.   
• 
Appropriate storage, restricted access and disposal arrangements for participant clinical 
details at the study sites. 
• 
Sites are responsible for ensuring only the instructed identifiers (study ID) are present 
when submitting data into RedCAP and that any data/documentation is appropriately 
anonymised in accordance with the study procedures to conform with the 1998 Data 
Protection Act.  
 
At the end of the study, personal data will be securely archived at the University of Bath (RedCAP) 
for 10 years. The archiving of all anonymised electronic data for a minimum of 10 years will be 
the responsibility of the Sponsor. Following authorisation from the Sponsor, arrangements for 
confidential destruction will then be made. It is the responsibility of each centre to maintain their 
file of patient identifiers on site or at their designated archive facility for this period of time. 
 
Timeline 
Phase 
Timeline 
Set up: ethics and site initiation 
February 2025- July 2025 
Data collection 
August 2025- November 2025 
Analysis/ Write up 
Dec 2025- April 2026 
 
Ethical approval 
This study will be conducted according to the principles of the Declaration of Helsinki, Good 
Clinical Practice (GCP), European Medicines Agency 2002 and current European Directives 
particularly 2001. We will obtain HRA ethical approval prior to the study initation and will register 
the study with the National Institute for Health and Care Research.  
Funding 
This project is funded by a British Skin Foundation fellowship awarded to Dr Charlotte 
Gollins (BSF Fellowship 001_F_23 ). 
 

 
 
Date: 28/07/2025 
 
 
 
 
 
 
 
 
 
 
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