Long-term sustainability of response to upadacitinib among patients with active rheumatoid arthritis refractory to biological treatments: results up to 5 years from SELECT-BEYOND

Abstract

Objective: To evaluate the long-term sustainability of response to the Janus kinase inhibitor upadacitinib among patients with rheumatoid arthritis and an inadequate response or intolerance to biological disease-modifying antirheumatic drugs (bDMARD-IR) in the SELECT-BEYOND phase 3 trial.

Methods: Patients on background conventional synthetic DMARDs (csDMARDs) were treated once daily with upadacitinib 15 mg or placebo. Patients who completed the week 24 visit could enter a long-term extension of up to 5 years. The sustainability of response was assessed based on achievement of Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and Disease Activity Score 28-joint count using C-reactive protein (DAS28 (CRP)) targets and evaluated up to week 260 in all patients receiving the approved upadacitinib 15 mg dose, including those randomised to upadacitinib 15 mg and those who switched from placebo to upadacitinib 15 mg at week 12.

Results: In this bDMARD-IR population, 45% (n=104/229) and 79% (n=172/219) of patients treated with upadacitinib 15 mg plus background csDMARD(s) achieved CDAI remission or CDAI low disease activity (LDA) at any point during the 5-year study, respectively. Of those who achieved CDAI remission/LDA, 25%/43% maintained their initial response through 240 weeks of follow-up after first achieving response. Most patients who lost remission or LDA were able to recapture that response by the cut-off date. Similar overall results were observed for SDAI and DAS28 (CRP). No strong predictors of response were identified.

Conclusions: Over three-quarters of bDMARD-IR patients achieved CDAI LDA with upadacitinib, and almost half of those maintained LDA through 240 weeks of follow-up. Remission was achieved by nearly half of all patients and maintained in approximately a quarter of those achieving remission.

Trial registration number: NCT02706847.

Keywords: Antirheumatic Agents; Rheumatoid Arthritis; Therapeutics.

Figure 1. Proportion of patients achieving disease activity targets up to 5 years in SELECT-BEYOND. Data include patients randomised to UPA 15 mg and those who switched from placebo to UPA 15 mg at week 12. The proportions of patients achieving CDAI, DAS28 (CRP) or SDAI responses at any point during the 5-year study period are shown. CDAI, Clinical Disease Activity Index; csDMARD, conventional synthetic DMARD; DAS28 (CRP), 28-joint Disease Activity Score based on C-reactive protein; DMARDs, disease-modifying antirheumatic drugs; QD, once daily; SDAI, Simplified Disease Activity Index; UPA, upadacitinib.

Figure 2. Kaplan-Meier analysis of time to loss of disease activity targets after the first occurrence of response. Results are for patients who had achieved CDAI remission/LDA, DAS28<2.6/≤3.2 or SDAI remission/LDA. Week 0 indicates the first occurrence of response. Data include patients randomised to UPA 15 mg and those who switched from placebo to UPA 15 mg at week 12; those receiving placebo who achieved disease activity targets before or at UPA start date were excluded from the analysis. Remission was defined as CDAI≤2.8 or SDAI≤3.3; LDA was defined as CDAI≤10 or SDAI≤11. CDAI, Clinical Disease Activity Index; DAS28 (CRP), 28-joint Disease Activity Score based on C-reactive protein; LDA, low disease activity; QD, once daily; SDAI, Simplified Disease Activity Index; UPA, upadacitinib.

Figure 3. Proportions of patients in different disease activity states among those who achieved initial CDAI, DAS28 (CRP) or SDAI response (Observed Case). Data include patients randomised to UPA 15 mg and those who switched from placebo to UPA 15 mg at week 12; those receiving placebo who achieved disease activity targets before or at UPA start date were excluded from the analysis. Data are reported as observed case, with discontinuation of upadacitinib due to lack of efficacy treated as a loss of response (censored at the last dose date). CDAI, Clinical Disease Activity Index; csDMARD, conventional synthetic DMARD; DAS28 (CRP), 28-joint Disease Activity Score based on C-reactive protein; DMARD, disease-modifying antirheumatic drug; HDA, high disease activity; LDA, low disease activity; MDA, moderate disease activity; QD, once daily; REM, remission; SDAI, Simplified Disease Activity Index; UPA, upadacitinib.

Figure 4. Proportions of patients who lost initial CDAI, DAS28 (CRP) or SDAI targets and either recaptured or failed to regain response by the cut-off date. Data include patients randomised to UPA 15 mg and those who switched from placebo to UPA 15 mg at week 12; those receiving placebo who achieved disease activity targets before or at UPA start date were excluded. CDAI, Clinical Disease Activity Index; csDMARD, conventional synthetic DMARD; DAS28 (CRP), 28-joint Disease Activity Score based on C reactive protein; DMARD, disease-modifying antirheumatic drug; QD, once daily; SDAI, Simplified Disease Activity Index; UPA, upadacitinib.