An international Delphi consensus to define a clinically appropriate definition of disease modification for plaque psoriasis

Dear Editor, Plaque psoriasis (PP) affects an estimated 29.5 million adults globally and carries a significant disease burden through associated comorbidities.1 Typically, treatment approaches follow the severity of the condition, with biologic agents usually reserved for use in patients with moderate-to-severe disease who have shown inadequate response to topical and phototherapy options.2, 3 With the rise of targeted biologic therapies on the IL23p19 pathway that demonstrate high levels of efficacy (in some cases with patients achieving a PASI 90/100 response within 12–16 weeks of initiation),4 questions have arisen as to whether PP can be controlled, modified or even brought into remission.5 However, PASI has limited utility within regular clinical settings and can demonstrate degrees of subjectivity and variability.6, 7 The aim of this study was to develop a definition of disease modification (DM) that could be applied within a clinical setting. A literature review was conducted in May 2021 to identify what trends exist that may define disease modification for PP. The search was conducted through the PubMed database. Fifty-nine studies were accepted, which were used to guide the expert-led discussion that followed. The discussion took place in October 2021 with eight experts (Study authors 1–8) in psoriasis care from Europe and North America involved. Using a modified Delphi methodology guided by an independent facilitator (Triducive Partners Limited), the panel developed six themes and 35 statements (Table 1) for wider testing which were independently reviewed by each member before being used to build a 4-point Likert scale survey. A total of 63 responses from across Europe and North America were analysed. From this, 22 statements attained very strong (≥90%) agreement, 10/35 strong (≥75%) agreement, and 3 statements fell below the established threshold (Figure 1). A sustained improvement in the disease course of plaque psoriasis resulting from a change in pathophysiology that minimises the need for treatment. In patients with moderate-to-severe plaque psoriasis, in the absence of precise biomarkers, disease modification may be evaluated by sustained BSA<1% / PGA 0/1 for >12 months following treatment cessation. BSA and PGA were chosen as measurements as they have been shown to be more effective and easier to use in a clinical setting over PASI.8, 9 Twelve months was agreed as the timeframe as evidence shows a patient can relapse at any point within 1 year.10 The panellists believe that these outcome statements provide an appropriate definition for DM in PP as they clearly define the goal and end point that both the clinician and patient can understand. Furthermore, this definition considers how DM can be determined at the end of an episode of treatment, within a framework for longer-term goals, and how these could be conducted and measured in the clinical setting. The next step will be to determine the validity of this definition by applying and evaluating it within a real-world clinical environment. The study was initiated and funded by Janssen Immunology. All authors (except for TS and NW) received honoraria from Janssen Immunology while undertaking this study. Janssen Immunology commissioned Triducive Partners Limited to facilitate the project and analyse the responses to the consensus statements in line with the Delphi methodology. KE has received research grants, served as a scientific adviser, and/or speaker for Abbvie, Almirall, Boehringer Ingelheim, BMS, Galderma, Lilly, Leo, Janssen, Pfizer, Novartis, Sanofi and UCB. MS has received honoraria for participating in Advisory boards and given lectures for Leo Pharma, Abbvie, Celgene, Eli Lilly, Novartis, Pfizer, UCB and Lipidor. KS has received consultancy/speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Aristea Therapeutics, Boehringer Ingelheim, Celgene, Eli Lilly, Evelo, Galderma, Janssen-Cilag GmbH, LEO Pharma, Novartis, Pfizer, Sanofi Genzyme, TFS Trial Form Support GmbH and UCB. CC has received research grants, served as a scientific adviser, and/or clinical study investigator for AbbVie, Actelion, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung, Sanofi and UCB. AWA has served as a research investigator, scientific advisor and/or speaker to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Mindera, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron and Pfizer. LP has received consultancy/speaker's honoraria from and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo-Pharma, Lilly, Novartis, Pfizer, Sandoz, Sanofi and UCB. RG has received consultancy/speaker's honoraria from and/or participated in clinical trials for Bausch Health, AbbVie, Janssen, Eli Lilly, Kyowa Kirin, Mallincroft, Novartis, Sanofi and Sun Pharma. KJ has acted as a consultant for and/or received honoraria from AbbVie, Aclaris, Allergan, Almirall, Amgen, Arena, Aristea, Asana, Aurigene, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Escalier, Galapagos, Janssen, Lilly, MoonLake Immunotherapeutics, Nimbus, Novartis, Pfizer, Sanofi, Sienna Biopharmaceuticals, Sun Pharma, Target-Derm, UCB, Valeant and Ventyx. KJ has received grant support (to The Rockefeller University) from AbbVie, Akros, Allergan, Amgen, Avillion, Biogen, Botanix, Boehringer Ingelheim, Bristol-Myers Squibb, Exicure, Innovaderm, Incyte, Janssen, Kyowa Kirin, Lilly, Nimbus Lackshmi, Novan, Novartis, PAREXEL, Pfizer, Regeneron, UCB and Vitae Pharmaceuticals. TS is a full time employee of Triducive Partners Limited. NW is a full time employee of Triducive Partners Limited. Research data are not shared. This is due to the anonymity and confidentiality of the Delphi methodology employed in this study.