The Japanese population was defined as patients with RA who were enrolled in Japan from three ongoing, multicenter, randomized, double-blind trials of upadacitinib: two methotrexate-controlled phase III studies that included subsets of patients from Japan (SELECT-EARLY and SELECT-MONOTHERAPY ) and one placebo-controlled phase IIb/III study conducted exclusively in Japan (SELECT-SUNRISE ).
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The purpose of this analysis was to assess the long-term safety of upadacitinib in patients with RA enrolled from Japan and compare this with the global (both Japan and ex-Japan) RA clinical trial population. It is therefore necessary to determine the long-term safety profile of upadacitinib in Asia to identify any region-specific safety signals. For example, a higher rate of infections, particularly herpes zoster, has previously been observed in patients treated with JAK inhibitors enrolled from clinical sites in Asia than patients enrolled from other regions. Adverse events of special interest (AESIs) with upadacitinib include serious infections, opportunistic infections, herpes zoster, malignancies, major adverse cardiovascular events (MACE), and venous thromboembolism (VTE).ĭifferences may exist in the safety profiles of JAK inhibitors in patients from Asia compared with global patients with RA. Upadacitinib has demonstrated clinical and functional efficacy in diverse RA populations, both in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and as monotherapy. Upadacitinib (ABT-494) is an oral JAK inhibitor engineered for greater selectivity for JAK1 versus JAK2, JAK3, and TYK2 based on in vitro analysis. The Janus kinase (JAK) family are important mediators of types I and II cytokine receptor signaling pathways involved in normal cellular processes as well as in the pathogenesis of rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. The safety profile of upadacitinib was generally similar between Japanese and global RA populations, except for higher EAIRs for serious adverse events and infections, including herpes zoster, in the Japanese population.
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Prior herpes zoster was a significant risk factor for herpes zoster. Herpes zoster rates were higher in the Japanese population (7.8, 12.4, and 16.7 per 100 PY with 7.5, 15, and 30 mg, respectively) versus global populations (3.7 and 7.0 per 100 PY with 15 and 30 mg, respectively). The exposure-adjusted incidence rates (EAIRs) of serious adverse events in the Japanese population were 11.5, 12.2, and 21.2 per 100 patient-years (PY) with upadacitinib 7.5, 15, and 30 mg, respectively.
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The Japanese population (mean age 57.0 years mean RA duration 6.1 years) received upadacitinib 7.5 mg ( n = 121), 15 mg ( n = 126), and 30 mg ( n = 124) once daily, while the global population (mean age 54.8 years mean RA duration 9.1 years) received upadacitinib 6 mg twice daily/15 mg once daily ( n = 2883) and 12 mg twice daily/30 mg once daily ( n = 1375). Pooled data in patients enrolled from Japan (the ‘Japanese population’ SELECT-SUNRISE, SELECT-EARLY, and SELECT-MONOTHERAPY) were compared with that from global (Japan and ex-Japan) upadacitinib clinical trial populations and summarized descriptively. The aim of this study was to assess the long-term safety of upadacitinib in patients with active RA from Japan compared with global clinical trial populations.
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Upadacitinib is a Janus kinase inhibitor with demonstrated efficacy in patients with rheumatoid arthritis (RA).