Improving clinical trial design in psoriasis: Perspectives from the global dermatology community

Abstract

Background: Clinical trials to test investigational drugs for the treatment of chronic plaque psoriasis currently lack standards for comparison of efficacy and safety data.The majority of studies do not address the important need for long-term treatment. Methods: The International Psoriasis Council (IPC) conducted two surveys of its members to assess the need for gold standards, active comparators, and long-term therapy in clinical trials. In Survey 1, 30 participants delivered viewpoints on active comparators for topical therapy (six questions), systemic therapy (nine questions), and continuous versus intermittent therapy (six questions). In Survey 2, 31 participants provided input on gold standards for treatment (five questions), appropriate comparators (four questions), and continuous versus intermittent therapy (six questions). The IPC leadership interpreted the results after each survey. Results: The majority of participants (77% in Survey 1 and 89% in Survey 2) agreed that studies of investigative treatments should include an active comparator. Participants described the most important feature of a gold standard as a treatment that: is widely used and generally accepted (45%); has the best efficacy (42%); and is well tolerated (13%). The majority agreed that gold standards should be dependent on: patient subgroup; location/extent of psoriasis; and psoriasis subtype/morphology. It was also agreed that continuous therapy for more than 3 years is needed for patients with moderate-to-severe plaque psoriasis. We have provided an expert opinion regarding the definition of a gold standard in psoriasis and have also established that no single treatment can be the gold standard across all subgroups and types of the disease. Conclusions: A single gold standard for the treatment of psoriasis does not exist. The complexity and heterogeneity of psoriasis requires different gold standards for the various manifestations of psoriasis and for subgroups of patients reconciling comorbidities. Of note, 17 experts out of 30 selected methotrexate as the most nominated gold standard amongst systemic agents. The experts support the election of an active comparator as one that is most efficacious over just the best in a particular class. In concordance, 87% of respondents agreed that good tolerability is therefore not the lead criterion for selection of an active comparator in favor of effectiveness and broad use. Patients with moderate-to-severe plaque psoriasis require continuous therapy; this statement was supported by 93% of the experts. Reasons for considering long-term therapy included appearance of comorbidities, impairment of quality of life, possibility of relapse, and subjective complaints such as itch, pain, and joint disease.

Key words::

• clinical trials
• control groups
• investigational drugs
• psoriasis

Acknowledgements

The IPC would like to thank the members who participated in the surveys. We also thank Julia R. Gage, PhD for assistance with writing the manuscript. CEMG is supported in part by the NIHR Manchester Biomedical Research Centre.

Funding sources: Unrestricted funding for this work was provided by Abbott, Amgen/Wyeth, Centocor, and Janssen-Cilag. These companies had no influence on the content or construction of this paper. Production of the manuscript was supported by the International Psoriasis Council.

Conflict-of-interest disclosures: Prof. van de Kerkhof has served as a consultant or speaker, or received grant support from Abbott Laboratories, Allmiral, Barrier Pharmaceutics, Celgene, Centocor Inc, Leo Pharma, Merck Serono, Schering-Plough, and Wyeth. Professor Barker has been a compensated consultant for Wyeth, Abbott, Janssen Cilag, Centocor, Schering-Plough, and Novartis. Professor Griffiths has received research support or has served as a consultant or speaker for Abbott, Amgen, Biogen-Idec, Centocor, Essex Pharma, Galderma, Incyte, Leo Pharma, Novartis, Novo Nordisk, Pfizer, Schering-Plough, Merck-Serono, Stiefel, UCB Pharma, and Wyeth. Dr Menter has served as a consultant, investigator, speaker or advisory board member for Abbott, Allergan, Amgen, Astellas, Asubio, Celgene, Centocor, DUSA, Eli Lilly, Galderma, Genentech, Novartis, Novo Nordisk, Pfizer, Promius, Stiefel, Syntrix Biosystems, Warner Chilcott, and Wyeth. Dr Leonardi has served as a consultant or speaker for Abbott, Amgen, Centocor, Genentech, and Warner Chilcott. He has been an investigator for Abbott, Allergan, Altana Pharma, Alza, Amgen, Astellas, Celgene, Centocor, Genentech, Bristol-Myers Squibb, Eli Lilly, Galderma, CombinatoRx, 3M Pharmaceuticals, Perrigo Israel Pharmaceuticals, Schering-Plough, Research Testing Laboratories, Novartis, Vitae Pharmaceuticals, and Wyeth. Ms Young is a consultant and/or speaker for Amgen, Abbott, Centocor, Ortho-McNeil-Janssen, and Coria Labs. Professor Kemeny has served as a consultant, investigator, speaker, or advisory board member for Abbott, Astellas, Barrier, Galderma, Leo Pharma, Novartis, Pfizer, Schering-Plough, Stiefel, UCB, and Wyeth. Professor Pincelli has served as a consultant and speaker for MerckSerono, Wyeth, Pfizer, and Creabilis Therapeutics. Dr Bachelez consulting activities for Abbott, Centocor, Janssen-Cilag, Leo Pharma, Merck-Serono, Schering-Plough, Wyeth-Pfizer. Professor Katsambas has served as a speaker or advisory board member for Abbott, Janssen-Cilag, Leo Pharma, Schering-Plough, Serono, Novartis, and Wyeth. Professor Ståhle has received research support or has served as a speaker or advisory board member for Abbott, Schering-Plough, Serono, Novartis, Janssen-Cilag, Wyeth, and Mölnlycke. Dr Horn consults with the International Psoriasis Council. Professor Sterry has served as a consultant, investigator, speaker or advisory board member for Abbott, Schering-Plough, Serono, Biogen-Idec, Novartis, Isotechnika, Fumedica, Janssen-Cilag, and Wyeth.