Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials

Abstract

Introduction: The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported outcome tool recommended for the assessment of disease activity in patients with rheumatoid arthritis (RA) in clinical practice. This analysis evaluated the long-term effect of upadacitinib vs. comparators on RAPID3 scores in patients with RA in the phase 3 SELECT clinical trial program.

Methods: This post hoc analysis included data from five randomized controlled trials (RCTs) in patients receiving upadacitinib 15 mg or 30 mg once daily (QD) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The proportions of patients reporting RAPID3 remission (scores ≤ 3) were assessed at week 60. Correlations between absolute scores for RAPID3 and Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) at week 60 were assessed using Spearman correlation coefficients.

Results: A total of 3117 patients were included from the SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE, and -EARLY trials. By week 60, 32-52% of methotrexate-naïve and csDMARD inadequate responder (IR) patients treated with either upadacitinib 15 mg QD or upadacitinib 30 mg QD reported RAPID3 scores consistent with remission. The proportions were slightly lower in the biologic DMARD-IR SELECT-BEYOND population (19-28%). RAPID3 scores highly correlated (Spearman correlation values ≥ 0.58) with CDAI, SDAI, and DAS28(CRP) scores through week 60 (all p < 0.001).

Conclusions: Upadacitinib, as monotherapy or in combination with csDMARDs, was associated with patient-reported remission assessed by RAPID3 over 60 weeks across the SELECT RCTs in patients with RA.

Trial registration: SELECT-BEYOND (NCT02706847); SELECT-NEXT (NCT02675426); SELECT-MONOTHERAPY (NCT02706951); SELECT-EARLY (NCT02706873); SELECT-COMPARE (NCT02629159).

Keywords: RAPID3; Rheumatoid arthritis; Upadacitinib.

© 2022. The Author(s).

Figures

Fig. 1

Percentage of patients in RAPID3 remission, LDA, MDA, and HDA across the SELECT trials at baseline and weeks 12/14, 24/26, and 60. Data are AO for SELECT-NEXT, -BEYOND, and -MONOTHERAPY, and LOCF for rescue patients then AO for SELECT-EARLY and -COMPARE. ADA adalimumab, AO as observed, bDMARD biologic disease-modifying antirheumatic drug, csDMARD conventional synthetic disease-modifying antirheumatic drug, EOW every other week, HDA high disease activity, IR inadequate response, LDA low disease activity, LOCF last observation carried forward, MDA moderate disease activity, MTX methotrexate, QD once daily, RAPID3 Routine Assessment of Patient Index Data 3, UPA upadacitinib

Fig. 2

Correlation between RAPID3 scores and A CDAI, B SDAI, and C DAS28(CRP) scores across the SELECT trials at week 60. Correlation coefficients of < 0.3 considered low correlation, 0.3–0.6 moderate, and > 0.6 high. Data are AO for SELECT-NEXT, -BEYOND, and -MONOTHERAPY, and LOCF for rescue patients then AO for SELECT-EARLY and -COMPARE. ADA adalimumab, AO as observed, CDAI Clinical Disease Activity Index, CI confidence interval, DAS28(CRP) 28-joint Disease Activity Score using C-reactive protein, EOW every other week, LOCF last observation carried forward, MTX methotrexate, QD once daily, RAPID3 Routine Assessment of Patient Index Data 3, SDAI Simplified Disease Activity Index, UPA upadacitinib

Fig. 3

Scores for components of composite measures of disease activity (CDAI, SDAI, and DAS28[CRP]) in patients with RAPID3 remission vs. patients not in RAPID3 remission at week 60. Remission/non-remission at week 60 determined through NRI. Component scores are AO for SELECT-NEXT, -BEYOND, and -MONOTHERAPY, and LOCF for rescue patients then AO for SELECT-EARLY and -COMPARE. ADA adalimumab, AO as observed, bDMARD biologic disease-modifying antirheumatic drug, CDAI Clinical Disease Activity Index, csDMARD conventional synthetic disease-modifying antirheumatic drug, DAS28(CRP) 28-joint Disease Activity Score using C-reactive protein, EOW every other week, hsCRP high-sensitivity C-reactive protein, IR inadequate response, LOCF last observation carried forward, MTX methotrexate, NRI non-responder imputation, PhGA Physician’s Global Assessment of Disease Activity, PtGA Patient’s Global Assessment of Disease Activity, QD once daily, RAPID3 Routine Assessment of Patient Index Data 3, SDAI Simplified Disease Activity Index, SJC28 swollen joint count for 28 joints, TJC28 tender joint count for 28 joints, UPA upadacitinib