POS1067 DOMAINS CONTRIBUTING TO MINIMAL DISEASE ACTIVITY ACHIEVEMENT IN PATIENTS WITH PSORIATIC ARTHRITIS RECEIVING GUSELKUMAB

Abstract

BackgroundDespite effective treatments, a minority of psoriatic arthritis (PsA) patients (pts) realize sustained minimal disease activity (MDA).1 Pt-driven domains of MDA are less frequently achieved, potentially arising from comorbid conditions.1ObjectivesIdentify domains contributing to and factors influencing MDA achievement in the 2-year Phase 3 DISCOVER-2 trial.MethodsRandomized and treated adults (N=739) had active PsA, were biologic/JAK inhibitor-naive, and had swollen and tender joint counts (SJC/TJC) each ≥5 and C-reactive protein ≥0.6 mg/dL. Pts with medical history of fibromyalgia (FM) were not excluded. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then every 8 weeks (Q8W); or placebo (PBO); PBO pts crossed over to GUS 100 mg Q4W at W24. MDA requires fulfillment of ≥5/7 criteria: TJC ≤1, SJC ≤1, Psoriasis Area and Severity Index (PASI) score ≤1, Pt Pain score ≤15, Pt global disease activity (PtGA) score ≤20, Health Assessment Questionnaire – Disability Index (HAQ-DI) score ≤0.5, and ≤1 tender entheses. A longitudinal trajectory of achieving each MDA criterion through W100 was derived (nonresponder imputation [NRI]). Time to achieve was estimated via Kaplan-Meier survival curve for scores deriving from native scales and those normalized to a 0-66 scale (corresponding to SJC). Multivariate regression models for time to achievement (cox proportional hazard) and achievement (logistic regression) of MDA at W100 identified predictors of response.ResultsAmong 492 GUS pts, continuous improvement across all MDA domains was shown through proportions of pts achieving criteria at W24 & W100 (NRI): SJC (45% & 65%), TJC (16% & 34%), PASI (71% & 72%), Pt Pain (23% & 37%), PtGA (29% & 45%), HAQ-DI (34% & 44%), entheseal points (75% & 80%). Times to achieve minimal SJC, PASI, and enthesitis with GUS were significantly faster than for PtGA, Pt Pain, TJC, and HAQ-DI for native-scale scores; when normalized, PtGA, Pt Pain, and HAQ-DI were achieved less often (Figure 1). Higher baseline (BL) Pt Pain score and lower BL Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score (worse fatigue) were significant predictors of longer time; lower BMI was associated with shorter time to achieve Pt Pain ≤15. Results for achieving Pt Pain ≤15 at W100 were similar. Worse baseline fatigue and PtGA were significant predictors of longer time to PtGA ≤20; worse fatigue also predicted non-achievement of PtGA ≤20 at W100. For time to achieve HAQ-DI ≤0.5, significant BL negative predictors were higher age and BL HAQ-DI score, which were also significant predictors of HAQ-DI ≤0.5 non-achievement at W100. Although seen in only a small number of pts, a significant impact of FM history and suicidal ideation/behavior on Pt Pain ≤15 and HAQ-DI ≤0.5, respectively, was observed (Table 1).Table 1.Predictors of Time to Achievement and Achievement of Recalcitrant MDA Domains at Week 100 in GUS-randomized Pts (N=492)Time to achievementIndependent BL VariablesPt Pain ≤15PtGA ≤20HAQ-DI ≤0.5HR (95% CI)HR (95% CI)HR (95% CI)Age-0.98 (0.97-0.99)†HAQ-DI-0.26 (0.19-0.36)‡PtGA VAS-0.99 (0.98-1.00)*-Pain VAS0.99 (0.98-1.00)†-FACIT-Fatigue§1.02 (1.00-1.03)*1.02 (1.01-1.04)‡-BMI0.98 (0.96-1.00)*FM (N=8)0.70 (0.55-0.90)†--Achievement at W100OR (95% CL)∥OR (95% CL)∥OR (95% CL)∥Age--0.98 (0.96: 1.00)*HAQ-DI--0.13 (0.08: 0.20)‡Pain VAS0.98 (0.97: 1.00)†--FACIT-Fatigue§1.02 (1.00: 1.05)*1.05 (1.03: 1.07)‡-BMI0.97 (0.94: 1.00)*--Suicidal Ideation/Behaviour (N=9)--0.16 (0.03: 0.86)*FM (N=8)0.59 (0.40: 0.86)†--HR Hazard Ratio CI Confidence Interval OR Odds Ratio CL Confidence Limits*p <0.05; †p <0.01; ‡p ≤0.0001§Higher score indicates less fatigue∥Wald CLConclusionGUS provided continuous improvement in each MDA domain through W100. BL domain score, as well as age, fatigue, and BMI, were significant determinants of MDA achievement in recalcitrant pt-driven domains (Pt Pain, PtGA, HAQ-DI). The impact of FM and mental health status merits further evaluation.