Background Sustained minimal disease activity (MDA) is achieved by a minority of patients (pts) receiving biologics for psoriatic arthritis (PsA) . Pt-reported MDA domains are less frequently achieved than physician-reported domains [2,3]. Here, we assessed MDA achievement in pts with PsA and inadequate response to 1–2 tumour necrosis factor inhibitors (TNFi-IR).
Objectives Identify PsA disease domains and factors contributing to the lack of MDA achievement at Week (W)48 for TNFi-IR PsA pts treated with guselkumab (GUS) using data from the Phase 3b COSMOS trial.
Methods In COSMOS, adults with active PsA (swollen/tender joint counts [SJC/TJC] each ≥3) and TNFi-IR were randomized 2:1 to subcutaneous GUS 100 mg or placebo (PBO) at W0, W4, then every 8 weeks. PBO pts crossed over to GUS at W16 (early escape) or W24 (planned). MDA was defined as fulfilment of ≥5/7 domains: tender entheses (Leeds Enthesitis Index [LEI]; 0–6) ≤1; Health Assessment Questionnaire – Disability Index (HAQ-DI; 0–3) ≤0.5; pt pain (0–100) ≤15; Psoriasis Area and Severity Index.
(PASI; 0–72) ≤1; Pt Global Assessment (PtGA; 0–100) ≤20; SJC (0–66) ≤1; and.
TJC (0–68) ≤1. Fibromyalgia (pFM) was defined at baseline (BL) using TJC minus SJC ≥7 as a proxy . A longitudinal trajectory of achieving each MDA domain through W48 was derived (non-responder imputation). Time to achieving each domain was assessed with.
Kaplan–Meier analyses; to account for differences in scales and domain strictness, scores were also normalized to SJC (0–66) scale. Response predictors (for pts not meeting each MDA domain criteria at BL) were identified using multivariate regression for time to achievement (Cox proportional hazards) and W48 achievement (logistic) of MDA.
Results GUS pts (n=189) showed improvement from BL in all MDA domains, with overall W24/48 response rates (%) of: LEI (74.5/79.8), HAQ-DI (26.1/37.0), pt pain (14.7/30.6), PASI (66.8/81.5), PtGA (24.5/39.9), SJC (46.2/63.0) and TJC (14.7/28.3) respectively. Times to achievement of minimal scores for LEI, SJC and PASI were faster than for PtGA,
HAQ-DI, pt pain and TJC for native-scale scores; when normalized, PtGA, HAQ-DI and pt pain showed a slower response (Figure 1). Higher BL HAQ-DI and worse fatigue (lower functional assessment of chronic illness therapy [FACIT]-fatigue score) were significantly associated with longer time to HAQ-DI ≤0.5; these factors plus older age predicted W48 non-achievement of HAQ-DI ≤0.5 (Table 1). Worse BL pt pain and fatigue were significant predictors of longer time to pt pain ≤15; these factors plus pFM predicted W48 non-achievement of pt pain ≤15. Worse BL fatigue was also significantly associated with longer time to PtGA ≤20 and W48 non-achievement of PtGA ≤20. Higher TJC, methotrexate (MTX) use and no pFM at BL were significantly associated with longer time to TJC ≤1; higher BL TJC, MTX and older age predicted W48 non-achievement of.
Conclusion GUS provided sustainable improvement in all MDA domains through W48. Physician-reported domains (LEI, PASI and SJC) were achieved faster than pt-driven domains (PtGA, HAQ-DI, pt pain and TJC). BL domain scores, worse fatigue and MTX use (for TJC only) were inversely correlated with MDA in the refractory domains.
References Rahman P et al. BMJ Open 2017;7:e016619
Coates L et al. Ann Rheum Dis 2022;81:856–7
Kavanaugh A et al. Arthritis Rheumatol 2022;74(S9)
Disclosure of Interests Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Carlo Selmi Speakers bureau: AbbVie, Amgen, Alfa-Wassermann, Biogen, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, SOBI, Paid instructor for: Amgen, Eli Lilly, Janssen, Novartis, Consultant of: AbbVie, Amgen, Alfa-Wassermann, Biogen, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, SOBI, Grant/research support from: AbbVie, Amgen, Pfizer, Georg Schett: None declared, Pascal Richette Speakers bureau: UCB, Janssen, Pfizer, Abbvie, Lilly, Novartis, Consultant of: UCB, Janssen, Pfizer, Abbvie, Lilly, Novartis, Julio Ramírez Speakers bureau: Abbvie, UCB, Janssen, Novartis, Pfizer, Angem and Lilly, Paid instructor for: Novartis and Janssen, Consultant of: Janssen, Novartis, Abbvie and UCB, Grant/research support from: Pfizer, Wim Noel Shareholder of: Johnson and Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson and Johnson, Emmanouil Rampakakis Consultant of: Employee of JSS Medical Research, a contract research organization (CRO) providing services to pharmaceutical and biotechnology stakeholders, Miriam Zimmermann Employee of: Janssen Pharmaceutical Companies of Johnson and Johnson, Mohamed Sharaf Employee of: Janssen Pharmaceutical Companies of Johnson and Johnson, Dennis McGonagle Speakers bureau: Abbvie, Celgene, MSD, UCB, Lilly, Novartis, Janssen, Paid instructor for: Abbvie, Celgene, MSD, UCB, Lilly, Novartis, Janssen, Grant/research support from: Abbvie, Celgene, MSD, UCB, Lilly, Novartis, Janssen.
- Clinical trials
- Psoriatic arthritis
- Outcome measures
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