Upadacitinib in Rheumatoid Arthritis: Dose-Specific Pooled Findings

Key Takeaways

• Both 15 mg and 30 mg once daily were associated with improved ACR20 response at 12 weeks versus control.
• No significant efficacy difference was observed between the two doses in the direct pooled comparison.
• Adverse events rose with dose, and serious infections, herpes zoster, and elevated liver enzymes were more frequent with 30 mg; the authors favored 15 mg on benefit-risk grounds.

In rheumatoid arthritis, a systematic review and meta-analysis found that both once-daily upadacitinib doses improved 12-week ACR20 response versus control, with 15 mg associated with an OR of 4.09. The pooled evidence included nine randomized controlled trials and 5,237 participants. Across the trials, direct comparison of 15 mg and 30 mg did not show a significant efficacy difference. Similar efficacy was observed with both doses, while pooled safety outcomes were less favorable with 30 mg.

The analysis examined dose-specific efficacy and safety of orally administered upadacitinib, a selective JAK1 inhibitor, in rheumatoid arthritis. Investigators followed PRISMA methods and searched PubMed, Web of Science, and Embase from inception to July 2025. The protocol was registered as PROSPERO registration CRD420251134541, and analyses were run in RevMan 5.4, with fixed-effects or random-effects models selected by heterogeneity. The primary endpoint was ACR20 response at 12 weeks, and predefined secondary safety outcomes included overall adverse events, serious infections, herpes zoster, and laboratory abnormalities.

In pooled efficacy analyses, both dose groups showed statistically significant improvement versus control at 12 weeks. The 30-mg regimen was associated with an OR of 3.61. When the two regimens were compared directly, the odds ratio was 1.00 and the P value was 0.98, indicating no significant efficacy difference. Short-term clinical response was similar with 15 mg and 30 mg at the assessed 12-week outcome.

Safety findings showed a dose-dependent rise in adverse events, with overall event odds ratios of 1.30 for 15 mg and 1.42 for 30 mg. Serious infections, herpes zoster, and elevated liver enzymes were more frequent in the 30-mg group. The authors also noted that further studies are needed to clarify long-term outcomes and safety in specific patient populations. Within these pooled data, they concluded that the 15-mg regimen may offer a more favorable benefit-risk balance.