Evolution of the inclusion/exclusion criteria and primary endpoints in pivotal trials of biologics and small oral molecules for the treatment of psoriasis

ABSTRACT

Introduction: Primary endpoints and inclusion/exclusion criteria of biologics and small oral molecules for psoriasis treatment have been evolving due to a better understanding of the pathogenesis and potential risks.

Areas covered: We analyzed the designs of key phase 3 pivotal trials of all biologics and small oral molecules approved for moderate to severe plaque psoriasis from published data on the ClinicalTrials.gov website and literature in the PubMed database. Alefacept, efalizumab, anti-tumor necrosis factors, anti-interleukin (IL)-12/IL-23, anti-IL-17 and anti-IL-23 inhibitors were discussed chronologically. Small oral molecules including tofacitinib and apremilast were also reviewed.

Expert opinion: The primary endpoints of trials of biologics have been raised progressively and psoriasis area and severity index (PASI) 100 can now be readily achievable by the recent biologics. For safety, 5-year observation periods have become a gold standard after the report of progressive multifocal leukoencephalopathy after efalizumab. Also, the need for tuberculosis (TB) prophylaxis has also been relaxed in one trial of risankizumab. Small oral molecules are the future of affordable effective treatment for psoriasis, but the safety concerns must be overcome as reflected by their more stringent exclusion criteria. More biologic switch data and inclusion of patients previously excluded, e.g. viral hepatitis, are still needed.

KEYWORDS:

• Alefacept
• anti-interleukin
• anti-tumor necrosis factor
• apremilast
• biologics
• clinical trials
• design
• efalizumab
• psoriasis
• tofacitinib

Article Highlights

• Primary endpoints have evolved progressively from PASI 75 to PASI 100 for biologic treatment for psoriasis.

• Use of biologics as the active comparators are incorporated following regulatory requirement and for marketing purpose.

• Randomized controlled pivotal studies with subsequent open-label extension into 5 years are the standard designs to verify the long-term safety.

• An increase in trials of biologic switch is observed to reflect current clinical needs.

• Incorporation of hepatitis B DNA and hepatitis C RNA testing as a pre-trial screening tool other than serology exams becomes more prevalent in newer trials.

Declaration of Interest

S-H. Hsu has received speaking fees from AbbVie, Janssen-Cilag, Leo Pharma and Novartis. T-F. Tsai has been a consultant for AbbVie, Boehringer Ingelheim, Celgene, Eli-Lilly, Galderma, GSK, Janssen-Cilag, Leo Pharma, Merck-Serono, Novartis International AG, and Pfizer Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Declarations

A reviewer on this manuscript has disclosed that they have received research, speaking and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Alvotech, Leo Pharma, BMS, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Ortho Dermatology, Abbvie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate and National Psoriasis Foundation. They have also disclosed acting as a consult for others through Guidepoint Global, Gerson Lehrman and other consulting organizations. They have also been a founder and majority owner of www.DrScore.com, and a founder and part-owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment.

Additional information

Funding

This paper was not funded.