Ab1122 guselkumab vs golimumab in psa tnfi-inadequate responders (evolution): formulating a pragmatic phase 3b randomized trial

Background Aside from the Tight Control in PsA (TICOPA) study, treatment strategy trials in psoriatic arthritis (PsA), and definitive guidance on managing patients (pts) with inadequate response (IR) to a first tumor necrosis factor inhibitor (TNFi), are lacking. Recent observational studies suggest potentially greater benefit from switching TNFi-IR pts to a new mechanism of action (MOA). [1] Objectives Design a pragmatic trial (EVOLUTION) to determine whether switching TNFi-IR PsA pts to a new MOA, specifically to the selective interleukin 23 inhibitor (IL-23i) guselkumab (GUS), is more effective than cycling to a 2 nd TNFi (Figure 1). Methods To plan the EVOLUTION trial, we assessed pts receiving any biologic in the multicenter longitudinal observational Psoriatic Arthritis Research Consortium (PARC) study. [2] Findings informed expected mean changes in selected outcome measures, enrollment feasibility, and sample size estimates. Results 215 pts initiating a biologic in PARC (including later lines of therapy) had data for the outcomes of interest and a 3-6 month follow-up visit. At therapy initiation (baseline [BL]), mean age=50.4 (SD 14.4), 56% were female, 81% were White. Mean BL clinical disease activity in PsA (cDAPSA)=20.0 (15), mean body surface area (BSA)=2.0% (6), 21% were in minimal disease activity (MDA), 43% were in cDAPSA remission/low disease activity (LDA), and 70% had a BSA ≤1%. 113/215 (53%) pts met EVOLUTION’s clinical enrollment criteria (Figure 1). Pts who would be eligible for EVOLUTION vs ineligible pts had higher disease activity (mean cDAPSA 29.0 vs 10.0, PtGA 5.6 vs 3.1, Psoriatic Arthritis Impact of Disease Questionnaire [PSAID-12] 5.1 vs 2.6, swollen joint count [SJC] 6.0 vs 0.8, tender joint count [TJC] 11.0 vs 2.4); age and sex distribution were similar. Among EVOLUTION-eligible pts not in MDA at BL, 21% achieved MDA at follow up. Also at follow-up in EVOLUTION-eligible pts not in response at BL, 38% achieved cDAPSA LDA, 38% achieved BSA ≤1%, 30% achieved both, and mean change (Δ) in PtGA= -1.0 (2.5), Δ pt pain= -1.4 (2.7), and Δ PSAID-12= -1.0 (1.9). EVOLUTION’S primary study outcome (cDAPSA LDA + IGA 0/1) will be assessed at 12 months (Table 1), and per clinical practice, pts will be enrolled at the time of switch vs post-washout. Assuming 24%, 45% and 50% of pts in the golimumab (GOL), GUS Q8W and GUS Q4W arms, respectively, would achieve the primary outcome, and a 20% pt dropout rate, a total sample size of 300 pts is anticipated to yield 80 pts per randomized group and provide 80% power to detect a difference in proportions of GUS Q4W vs GOL and GUS Q8W vs GOL pts achieving cDAPSA LDA + IGA 0/1. Conclusion The EVOLUTION trial will apply an innovative, pragmatic randomized trial approach to assessing therapy effectiveness by recruiting a treatment-refractory PsA population consistent with that seen in clinical practice. This also includes using a novel primary endpoint (cDAPSA LDA + IGA 0/1) with direct applicability to routine care. This first of its kind head-to-head comparative effectiveness trial in real-world PsA pts will address important knowledge gaps in the management of PsA related to switching from a TNFi to GUS vs cycling to a 2 nd TNFi and will build on a longitudinal cohort study used to plan this study. References [1]Ogdie A, et al. Arthritis Rheumatol. 2022;74(suppl 9) A1600. [2]Walsh JA, et al. J Rheumatol . 2020;47:1496-1505. Table 1. EVOLUTION Endpoints Primary outcome cDAPSA LDA + IGA 0/1 at 12 months Secondary endpoints at 6 and 12 months cDAPSA LDA + IGA 0/1 (6 months) MDA, PSAID-12 <4, Δ PSAID-12, IGA 0/1 in pts with BSA >3% at BL, IGA in pts with IGA ≥2 at BL, Δ PROMIS-Fatigue, Δ DLQI, Δ BASDAI in pts with axial disease, dactylitis resolution, enthesitis resolution, drug retention, AE, tolerability Qualitative process evaluation Qualitative interviews on trial format, engagement and participation PSAID-12 (PSAID <4 is the pt acceptable symptom state); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); Dermatology Life Quality Index (DLQI); Pt-Reported Outcomes Measurement Information System (PROMIS) Acknowledgements This work was supported by Janssen Scientific Affairs, LLC (CNTO1959PSA3006; NCT05669833 ) and represents a collaboration between the authors and funders. Disclosure of Interests Alexis Ogdie Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, CorEvitas, Gilead, GlaxoSmithKline, Happify Health, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Janssen, Pfizer and Novartis and to Forward from Amgen, Soumya Reddy Consultant of: AbbVie, Amgen, Fresnius Kabi, Janssen, Novartis, and UCB, Kathleen Bush: None declared, Sarah Hopkins Gillespie: None declared, M Elaine Husni Consultant of: AbbVie, Genzyme/Regeneron, Janssen, Novartis, Eli Lilly, Sanofi, and UCB, Paras Karmacharya: None declared, Jose Scher Consultant of: AbbVie, Janssen, Kaleido, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: Janssen, Novartis, and Pfizer, Michelle Perate Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Cinty Gong Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Jessica A. Walsh Consultant of: AbbVie, Janssen, Eli Lilly, Novartis, and UCB, Grant/research support from: AbbVie, Merck, and Pfizer.