A NOVEL COMPOSITE ENDPOINT INCLUDING LOW PERIPHERAL JOINT DISEASE ACTIVITY STATE AND CLEAR/ALMOST CLEAR SKIN IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: POST HOC ANALYSES OF 2 PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDIES

Background: Composite indices are valuable tools to assess the heterogeneity of PsA. The PsA Disease Activity Score (PASDAS)[1] comprehensively assesses joint and skin domains but is cumbersome to use in clinical practice. The Clinical Disease Activity Index for PsA (cDAPSA),[2] a composite measure excluding CRP and thus relatively easy to use in clinical practice, focuses on peripheral joint disease but does not assess the skin. A novel composite endpoint combining cDAPSA and Investigator’s Global Assessment (IGA) of psoriasis (PsO) has been proposed as a tool for both skin and joint disease activity that is feasible for use in clinical practice and is being used in an ongoing pragmatic trial. [3] Objectives: (1) Compare achievement of cDAPSA low disease activity (LDA; score ≤13, including remission) + IGA 0 or 1 (IGA 0/1; range=0 [clear] to 4 [severe]) among patients (pts) receiving guselkumab (GUS) vs. placebo (PBO); (2) contrast performance of cDAPSA LDA+IGA 0/1 vs. PASDAS LDA (≤3.2); (3) assess earlier cDAPSA LDA+IGA 0/1 response as predictor of future stringent disease control. Methods: Adults with active PsA despite standard nonbiologic therapies enrolled in DISCOVER-1 (31% TNFi-experienced) & DISCOVER-2 (biologic-naive) were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, Q8W; or PBO with crossover to GUS 100 mg Q4W at W24. Pts with cDAPSA ≥13 and IGA >1 at baseline (BL) were included in these post hoc analyses. cDAPSA LDA+IGA 0/1 response was summarized by randomized group. Pts who discontinued study agent or participation or initiated protocol-prohibited PsA treatments through W24 were considered nonresponders, as were pts with missing data from W24-W52. GUS vs PBO response rates through W24 were compared with logistic regression adjusted for prior TNFi use and cDAPSA score, IGA score, and conventional synthetic (cs) DMARD use at BL (nominal p values). Agreement between cDAPSA LDA+IGA 0/1 and PASDAS LDA was assessed with Cohen’s kappa, % concordance, sensitivity, and specificity (ref: PASDAS LDA). Among GUS-randomized pts, the predictive value of W16 cDAPSA LDA+IGA 0/1 or PASDAS LDA for achieving ACR50/70, 100% improvement in PsO Area and Severity Index (PASI 100), pt global assessment (PtGA) ≤20mm, HAQ-DI normalization (≤0.5), and Minimal Disease Activity (MDA) was assessed using logistic regression adjusted for prior TNFi use and BL disease activity and csDMARD use. Results: At W8 (first PASDAS timepoint), PASDAS LDA was met by 12%/ 9% of GUS (Q4W/ Q8W) vs 2% of PBO pts (both p≤0.001) (Figure 1 ). At W16 (first IGA assessment), cDAPSA LDA+IGA 0/1 was achieved by 25%/ 28% of GUS (Q4W/ Q8W) vs 6% of PBO pts (both p<0.001); corresponding W16 rates for PASDAS LDA were 22%/ 21% vs. 5% (both p<0.001). Response rates for both endpoints continued to increase through W52 of GUS. Cohen’s kappa (0.72) and 88% concordance indicated substantial agreement between cDAPSA LDA+IGA 0/1 and PASDAS LDA, with high sensitivity and specificity (both 88%) for the novel endpoint. Pts achieving cDAPSA LDA+IGA 0/1 at W16 were significantly more likely to achieve stringent disease control at W52 than pts without W16 response; odds ratios for achievement of ACR50/70, PASI 100, PtGA ≤20mm, HAQ-DI ≤0.5, and MDA responses at W52 were similar between W16 cDAPSA LDA+IGA 0/1 and PASDAS LDA responders. Conclusion: GUS was associated with early induction of a low joint+skin disease activity state and increasing response rates through 1 year across composite measures. cDAPSA LDA+IGA 0/1 showed substantial agreement with PASDAS LDA, and achievement of either outcome at W16 predicted later stringent disease control. Achievement of cDAPSA LDA+IGA 0/1 during GUS treatment was comparable to that of DAPSA LDA+IGA 0/1.[4] The novel composite endpoint of cDAPSA LDA+IGA 0/1 has construct and convergent validity and may be a practical predictor of long-term PsA joint and skin response. REFERENCES: [1] Helliwell PS. Ann Rheum Dis. 2013;72:986. [2] Schoels MM. Ann Rheum Dis. 2016 May;75:811. [3] Ogdie A. Ann Rheum Dis. 2023;82:1791. [4] Boehncke WH. Ann Rheum Dis. 2022;81:261. Acknowledgements: NIL. Disclosure of Interests: Daniel Aletaha Received speaker fees from: AbbVie, Gilead, Galapagos, Eli Lilly, Janssen, Merck, and Novartis, consultant of: AbbVie, Gilead, Galapagos, Eli Lilly, Janssen, Merck, and Novartis, received grant/research support from: AbbVie, Gilead, Galapagos, Eli Lilly, Janssen, Merck, and Novartis, Joseph F. Merola Consultant of: AbbVie, Amgen, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Janssen, Leo, Novartis, Pfizer, Sanofi-Regeneron, Sun, and UCB, Received grant/research support from: AbbVie, Amgen, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Janssen, Leo, Novartis, Pfizer, Sanofi-Regeneron, Sun, and UCB, Mohamed Sharaf Employee of: Janssen MEA, Dubai United Arab Emirates, Natalie J. Shiff Owns stock in: AbbVie, Gilead, Iovance, Jazz, Johnson & Johnson, Novavax, and Viatris, employee of: Janssen Scientific Affairs, LLC, Emmanouil Rampakakis Employee of: JSS Medical Research, Inc, consultant of: Janssen, Francois Nantel Shareholder of: Johnson & Johnson, consultant of: Janssen, Frédéric Lavie Owns stock or stock options in: Johnson & Johnson, employee of: Immunology Global Medical Affairs, Janssen Cilag Global Medical Affairs, Anna Moltó Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, and UCB, Alexis Ogdie Royalties from: Novartis (husband), consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, CorEvitas, Eli Lilly, Gilead, Happify, Janssen, Novartis, Pfizer, and UCB, received grant/research support to the University of Pennsylvania from: AbbVie, Janssen, Novartis, and Pfizer, received grant/research support to Forward from: Amgen and Bristol Myers Squibb. DOI: 10.1136/annrheumdis-2024-eular.24 Keywords: Biological DMARD, Clinical Trial, Skin, Randomized controlled trial Citation: , volume 83, supplement 1, year 2024, page 373Session: Clinical Poster Tours: Clinical aspects of psoriatic arthritis (Poster Tours)

Biological DMARD, Clinical Trial, Skin, Randomized controlled trial