Efficacy and safety of upadacitinib in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE): a placebo-controlled phase IIb/III study

Abstract

Objective To evaluate upadacitinib efficacy and safety dose response in Japanese patients with active RA and an inadequate response to conventional synthetic DMARDs (csDMARDs). Methods This was a multicentre, phase IIb/III, dose-ranging study conducted in Japan, in which patients on previously stable csDMARDs were randomized to receive upadacitinib 7.5, 15 or 30 mg once daily or matching placebo for a 12-week double-blind period. The primary endpoint was a 20% improvement in ACR criteria (ACR20) response at week 12 using non-responder imputation. Key secondary endpoints included ACR50, ACR70 and 28-joint DAS with CRP (DAS28-CRP) remission and low disease activity. Adverse events were also assessed. Results Of 197 patients treated, 187 completed the double-blind period. At week 12, more patients receiving upadacitinib 7.5, 15 or 30 mg vs placebo met the ACR20 response (75.5%, 83.7%, 80.0% vs 42.9%; P < 0.001), with significant differences observed as early as week 1. Stringent responses, including ACR50, ACR70 and DAS28-CRP <2.6, were achieved by significantly higher proportions of patients on upadacitinib than placebo and by numerically higher proportions on upadacitinib 15 or 30 mg vs upadacitinib 7.5 mg. Adverse events and infections (serious infections, opportunistic infections and herpes zoster) were more common with upadacitinib vs placebo and numerically highest with upadacitinib 30 mg. There were no venous thromboembolic events reported. Conclusion Efficacy of upadacitinib was demonstrated in this population of Japanese patients with RA and an inadequate response to csDMARDs. Safety and tolerability were consistent with other upadacitinib RA studies. The 15 mg dose of upadacitinib showed the most favourable benefit–risk profile. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02720523.

A review of upadacitinib in rheumatoid arthritis

“…The majority of herpes zoster cases were non-serious and involved a single dermatome, with no central nervous system involvement observed. Herpes zoster appeared to be more common in Japanese patients compared with patients from other regions [32]. Types of serious infection were consistent with what would be expected in patients with RA and included opportunistic infections, active tuberculosis, invasive fungal infections, and bacterial and virus infections, with pneumonia being the most common [33].…”

“…A total of 197 patients with an IR to csDMARDs were randomized to placebo or upadacitinib 7.5 mg, 15 mg, or 30 mg once daily in combination with csDMARDs for 12 weeks. All upadacitinib doses met the primary endpoint of ACR20 response at week 12 compared with placebo (75.5%, 83.7%, and 80.0% versus 42.9%; p<.001) [32]. However, the 7.5 mg dose of upadacitinib did not improve rates of more stringent endpoints such as remission defined by Simplified Disease Activity Index (SDAI) or CDAI, whereas significant differences in these endpoints were seen in the 15 mg and 30 mg groups.…”

“…In contrast to the global phase III studies, the SELECT-SUNRISE study was performed exclusively in Japanese patients with RA [32]. A total of 197 patients with an IR to csDMARDs were randomized to placebo or upadacitinib 7.5 mg, 15 mg, or 30 mg once daily in combination with csDMARDs for 12 weeks.…”

Upadacitinib versus placebo or adalimumab with background methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate: a subgroup analysis of a phase III randomized controlled trial in Central and Eastern European patients

“…HZ infection in the upadacitinib group appeared to be slightly less common in the CEE population than in the global population (2.3 versus 3.1 per 100 PY). This may be expected as the global population includes Asian patients who have a known increased risk of HZ infection with JAK inhibitors, 9 , 23 , 24 whereas there were no Asian patients included in the CEE population.…”

“…3 Upadacitinib has demonstrated a generally favorable benefit–risk profile across various patient populations in phase III trials. 4 – 9 The molecule has recently been approved for the treatment of RA by the European Medicines Agency and the US Food and Drug Administration. 3 , 10…”