Ab1095 impact of psoriatic arthritis manifestations on perception of pain improvement: pooled analysis of two phase 3, randomized, double-blind, placebo-controlled studies with guselkumab

Background Pain in PsA has multifaceted origins (e.g., peripheral joint inflammation, axial involvement [axPsA], skin lesions, dactylitis, enthesitis, underlying conditions) and can be difficult to treat. Guselkumab (GUS), a fully human IL-23p19 subunit inhibitor, is effective in treating multiple PsA domains and elicited durable improvement in patient (pt)-reported pain (PtP) in the DISCOVER (D)-1&2 trials [1,2] . Objectives Assess association between improvement in key PsA manifestations and PtP using 1-year D1&2 data. Methods D1&2 enrolled adults with active PsA despite standard therapies [3,4] . Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo with crossover to GUS 100 mg Q4W at W24. Treatment groups were pooled (N=1120). Longitudinal associations of improvement in SJC (0-66), TJC (0-68), Leeds enthesitis index (LEI), dactylitis severity score (DSS), Psoriasis Area and Severity Index (PASI), axPsA (N=312), and improvement in overall PtP (0-100 mm) and spinal pain (BASDAI question 2 in pts with axPsA) were assessed. Longitudinal associations of improvement in these PsA manifestations with ≥30%/50%/70% improvements in PtP (PtP-30/50/70) were assessed. Results Mean (SD) BL PtP of 61.2 (19.8) indicated substantial burden. Upon adjusting for potential confounders, greater improvement in PASI, SJC, and TJC (mutually adjusted) were each associated with significantly greater improvement in PtP and higher odds of achieving PtP-30 through W52 (Table 1 ). PASI reduction was also associated with greater odds of PtP-50, as was TJC improvement for PtP-50/70. In pts with BL enthesitis, LEI, PASI, and TJC improvements were each associated with greater PtP improvement and attaining PtP-30/50/70; SJC reduction was only associated with PtP-30. In pts with BL dactylitis, PASI and TJC reductions were significantly associated with PtP improvement. Overall, axPsA presence did not impact the extent of PtP improvement (data not shown). In pts with axPsA, significant associations were observed between spinal pain improvement and TJC and LEI improvement. Conclusion Improvements in key PsA manifestations were significantly associated with pain reduction, although to varying extents. TJC reduction had the greatest impact on PtP improvement, likely due to overlap of the construct measured. Psoriasis improvement had a greater impact on pain relief than SJC improvement, highlighting the sensory burden of skin lesions, while enthesitis improvement showed a significant association with both overall and spinal pain relief. These findings underscore the importance of utilizing treatments effective across manifestations to address recalcitrant PsA symptoms. References [1]Ritchlin CT. RMD Open 2022;8:e002195 [2]Nash P. ACR Convergence 2021 (PO1333) [3]Deodhar A. Lancet 2020;395:1115 [4]Mease PJ. Lancet 2020;395:1126 Table 1. Adjusted 1 Associations Between Improvements in Key PsA Manifestations and Pain Improvement Through W52 Pt Population Predictor (Δ) Δ PtP (β) 2 Odds Ratio (OR) 3 Δ Spinal Pain (β) 2,4 PtP-30 PtP-50 PtP-70 All (N=1120 ) PASI 0.41 ‡ 1.05 † 1.04 † 1.04 0.03 SJC 0.28 † 1.03 * 1.03 1.06 0.03 TJC 0.55 ‡ 1.05 ‡ 1.08 ‡ 1.12 ‡ 0.06 ‡ BL Enthesitis (N=728 ) LEI 1.62 ‡ 1.19 ‡ 1.25 ‡ 1.32 ‡ 0.18 † PASI 0.47 ‡ 1.06 † 1.06 † 1.06 * 0.02 SJC 0.28 † 1.03 * 1.03 1.03 0.03 TJC 0.39 ‡ 1.04 ‡ 1.05 ‡ 1.08 ‡ 0.05 ‡ BL Dactylitis (N=473 ) DSS -0.04 0.97 * 1.01 1.07 0.01 PASI 0.31 † 1.04 * 1.05 * 1.05 0.02 SJC 0.19 1.03 1.03 1.02 0.05 * TJC 0.60 ‡ 1.05 ‡ 1.06 ‡ 1.11 ‡ 0.05 † * p<0.05; † p<0.01; ‡ p≤0.0001 1 Adjusted for BL values, age, gender, BMI, SF-36 Mental Component Summary score, presence of TJC – SJC ≥7 (central pain sensitization proxy), FACIT-Fatigue score, and treatment group 2 β correspond to the incremental increase in pain improvement; 3 ORs correspond to the incremental increase in the odds of achieving pain endpoints, for every increase in improvement in key PsA manifestations or in the presence (vs absence) of axPsA. Higher β = greater impact on pain improvement 4 N=312 Acknowledgements: NIL. Disclosure of Interests Peter Nash Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Gilead/Galapagos, GSK, Janssen, MSD, Novartis, Pfizer, Samsung, Sun Pharma, and UCB, Grant/research support from: AbbVie, Boehringer-Ingelheim, Eli Lilly, Gilead/Galapagos, GSK, Janssen, MSD, Novartis, Pfizer, Samsung, Sun Pharma, and UCB, Iain McInnes Shareholder of: Causeway Therapeutics and Evelo Compugen, Consultant of: AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb, Cabaletta, Compugen, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Amgen, Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Lai-Shan Tam Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Janssen, Pfizer, and Sanofi, Grant/research support from: Amgen, Boehringer-Ingelheim, GSK, Janssen, Novartis, and Pfizer, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Michael Starr Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Inc., Frederic Lavie Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, May Shawi Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Xenofon Baraliakos Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB.