FRI0138 THE IMPACT OF UPADACITINIB VERSUS METHOTREXATE OR ADALIMUMAB ON INDIVIDUAL AND COMPOSITE DISEASE MEASURES IN PATIENTS WITH RHEUMATOID ARTHRITIS

Abstract

Background:In Phase 3 trials, upadacitinib (UPA), an oral JAK1-selective inhibitor, has been assessed as monotherapy vs MTX (SELECT-EARLY1) and in combination with MTX vs adalimumab + MTX (ADA; SELECT-COMPARE2) in RA pts who were MTX naïve or with inadequate responses to MTX (MTX-IR), respectively.Objectives:In this analysis we assessed individual and composite measures of disease activity in SELECT-EARLY and SELECT-COMPARE.Methods:In SELECT-EARLY, MTX-naïve pts received UPA 15 mg or 30 mg monotherapy once daily (QD), or MTX monotherapy, for 12 wks. In SELECT-COMPARE, MTX-IR pts on stable background MTX received UPA 15 mg QD, PBO, or ADA 40 mg every 2 wks for 12 wks. For this analysis, responses at Wk 12 were defined as ≥50% improvement in the 7 components of the ACR response criteria. Among ACR50 responders, the proportions of pts with ≥50% improvement in all 7 components of the ACR criteria was assessed. The proportion of pts achieving TJC68=0 and SJC66=0 was also determined. All analyses were based on observed data without imputation.Results:947 pts were randomized in SELECT-EARLY, and 1629 pts in SELECT-COMPARE. Mean time since RA diagnosis was 2.7 years in SELECT-EARLY (median 6 months) and 8.2 years in SELECT-COMPARE; mean DAS28(CRP) was 5.9 and 5.8, respectively. In SELECT-EARLY, significantly more MTX-naïve pts receiving UPA 15 mg or 30 mg monotherapy achieved ≥50% improvements in all ACR components at Wk 12 compared with MTX (Figure 1a,Figure 1b). In SELECT-COMPARE, significantly more MTX-IR pts on UPA 15 mg + MTX achieved ≥50% improvement in the ACR components vs PBO (all components) and ADA + MTX (all components except SJC and PhGA). Among pts with ACR50 responses at Wk 12, approximately half of the MTX-naïve pts on UPA 15 mg and 30 mg in SELECT-EARLY had ≥50% improvements in all 5 remaining ACR components (pain, PtGA, PhGA, HAQ-DI, hsCRP) compared with 28% with MTX. Corresponding proportions in MTX-IR pts in SELECT-COMPARE were 34% for UPA 15 mg + MTX, 28% for ADA + MTX, and 17% for PBO. UPA treatment also significantly increased the proportions of pts achieving both TJC68=0 and SJC66=0 vs PBO or MTX, and SJC66=0 vs ADA + MTX (Figure 1a,Figure 1b).Conclusion:In MTX-naïve and MTX-IR pts, treatment responses at 12 wks occurred in significantly higher proportions of pts receiving UPA monotherapy vs MTX and UPA + MTX vs PBO for all 7 components of the ACR response criteria, and for 5 of 7 ACR components for UPA + MTX vs ADA + MTX. Favorable outcomes with UPA treatment were evident both in composite and individual parameters.