Biological Therapy Interruption and Re-Treatment in Chronic Plaque Psoriasis

October 2021 | Volume 20 | Issue 10 | Original Article | 1063 | Copyright © October 2021


Published online September 30, 2021

Charlie Yue Wang MBBSa, Peter Foley MD FACDa,b,c, Chris Baker MBBS FACDa,b,c, Marius Rademaker FRCP DMd

aDepartment of Clinical Trials, Skin Health Institute, Carlton, Victoria, Australia
bDepartment of Medicine (Dermatology), The University of Melbourne, Parkville, Victoria, Australia
cDepartment of Dermatology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia
dWaikato Clinical Campus, University of Auckland’s Faculty of Medical and Health Sciences Hamilton, Hamilton, New Zealand

Abstract
While biological treatments for chronic plaque psoriasis should be administered continuously to maximize and maintain efficacy, interruptions in therapy may be necessary for a number of reasons. We reviewed the evidence from clinical trials on efficacy, safety and immunogenicity in clinical trials for approved biologic agents for chronic plaque psoriasis. A systematic search of three major medical databases was performed and a total of 35 articles were included into the analysis, including 13 controlled trials. Trials assessing continuous therapy against dosing as-needed therapy (including infliximab, etanercept and secukinumab) have demonstrated superior efficacy for continuous regimes. However, randomized withdrawal trials for etanercept, adalimumab, ixekizumab, brodalumab, guselkumab, risankizumab and tildrakizumab, showed no significant impact on skin clearance rates in patients who are interrupted once and then re-treated. With the possible exception of infliximab, temporary interruption in biologic therapy appears to be safe and most agents will regain efficacy after re-introduction.

J Drugs Dermatol. 2021;20(10):1063-1071. doi:10.36849/JDD.5716

INTRODUCTION

Understanding of the immunologic basis of chronic plaque psoriasis has led to the development of several classes of biological agents, primarily monoclonal antibodies, including inhibitors of tumor necrosis factor (TNF), interleukin-12/23 (IL-12/23), interleukin-17 (IL-17), and interleukin-23 (IL-23).

Studies have explored alternate dosing regimens to improve adherence, however continuous therapy appears to be superior in efficacy compared to as-needed treatment for several agents.1-5 Nevertheless, temporary treatment interruption may occur in clinical practice for a number of reasons, such as elective surgery, hospitalization, illness such as COVID-19, pregnancy and breastfeeding, live vaccination, travel, and financial considerations. Conversely, some patients who have achieved and maintained skin clearance may request a trial off therapy. However, there are some concerns that interrupting biologic therapy may result in a subsequent diminished response and/or development of anti-drug antibodies. We reviewed the efficacy, safety and immunogenicity data of interrupted biologic therapy in clinical trials.

MATERIALS AND METHODS

A systematic review was performed according to PRISMA guidelines. An electronic search was conducted in the MEDLINE, Embase and ACP Journal Club databases, from date of inception to August 26, 2020. We combined the terms “psoriasis” with “infliximab, adalimumab, etanercept, certolizumab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, or tildrakizumab” and “withdraw, re-treat, interrupt, intermittent, or restart (and variations of each word root)”. Titles and abstracts were reviewed for relevant studies based on selection criteria, and full texts were reviewed to determine final inclusion. Reference lists from included articles were also reviewed for other relevant studies.

Selection Criteria
Final selection was based on five main criteria: full-text article in English (abstracts excluded), clinical trial (randomized controlled trials, non-randomized clinical trials or long-term extension trials), intervention (biologics in common use as outlined in the search), study population (chronic plaque psoriasis), and a withdrawal and re-treatment design in the study with available safety and efficacy data.

Data Extraction And Analysis
Data on study design, efficacy, and safety outcomes (including rate of response, rate of relapse, median time to relapse, safety profile, and rate of anti-drug antibodies) were extracted.

RESULTS

The initial database search yielded 678 results. After review of abstracts and titles, 40 relevant articles were identified, and