Clinical trial result revealed that upadacitinib may be more effective in treating patients with rheumatoid arthritis than the gold standard of care, methotrexate.
A clinical trial revealed that using upadacitinib as a monotherapy in patients with rheumatoid arthritis (RA) was a greater benefit to patients compared with methotrexate, the most commonly used initial therapy for RA.
Upadacitinib is a janus kinase (JAK) inhibitor that works to reduce inflammation caused by RA. It has been approved for treating patients with RA only after they’ve tried methotrexate.
“This trial convincingly demonstrates the efficacy of the JAK inhibitor upadacitinib as monotherapy in early rheumatoid arthritis. It works faster and better than methotrexate alone,” said Ronald van Vollenhoven, MD, lead investigator for the trial.
Although methotrexate is the most widely accepted initial RA therapy, it achieves remission in a minority of patients and acceptable disease control in at most 60% of patients. Some patients may have insufficient initial responses or are intolerant to methotrexate. About 80% of patients will lose response over time and other medications such as disease-modifying antirheumatic drugs (DMARDs) are often added to treatment regimens to combat this.
The SELECT-EARLY trial enrolled 947 patients with early stage RA who were treatment naïve to methotrexate. They were randomized to receive either 15 mg or 30 mg once daily of upadacitinib or weekly methotrexate for 24 weeks. Eighty-nine percent of enrolled patients completed the full 24 weeks.
The trial showed statistically significant and clinically meaningful improvements in both primary end points. Both doses of upadacitinib achieved a ≥50% response by week 12 (15 mg, 52%; 30 mg, 56%; P < .001) compared with methotrexate (28%; P < .001).
At week 24, 48% of patients receiving 15 mg upadacitinib and 50% of patients receiving 30 mg upadacitinib achieved a 28-joint Disease Activity Score of <2.6 compared with patients receiving methotrexate (19%, P < .001).
A significantly higher proportion of patients receiving either dose of upadacitinib compared to methotrexate also achieved low disease activity and remission by week 24 (15 mg: 24%; 95% CI, 20-29; 30 mg: 25%; 95% CI, 20-30; methotrexate: 7%; 95% CI, 4-10; P < .001).
Overall, 88% and 89% of patients receiving 15 mg or 30 mg of upadacitinib respectively had no radiographic progression. For patients receiving methotrexate, that number dropped to 78% (P < .01).
“These head-to-head data provide consistent evidence of the efficacy of this JAK inhibitor versus the gold standard of initial RA therapy, supporting the potential of upadacitinib as a new therapeutic option for patients with RA,” researchers said.
Additionally, the frequencies of treatment emergent adverse events (TEAEs) were similar between the 15 mg upadacitinib treatment arm and the methotrexate groups (65% vs 64%) but slightly higher in the upadacitinib 30mg treatment arm (71%).
Discontinuation due to TEAEs were comparable between all treatment arms (methotrexate: 5.1%; upadacitinib 15 mg: 4.4%; upadacitinib 30 mg: 3.8%).
A similar trend was observed for the frequency of serious adverse events. Acute myocardial infarction (methotrexate, n = 2; upadacitinib 30 mg, n = 1), pneumonia (methotrexate, n = 2; upadacitinib 15 mg, n = 1; upadacitinib 30 mg, n = 3), and osteoarthritis (upadacitinib 30 mg n = 2) were all reported in at least 1 patient in at least 1 treatment arm.
Development of serious infections such as pneumonia were higher among the upadacitinib 30 mg treatment arm and comparable between the 15 mg and the methotrexate treatment groups. A total of 6 deaths were reported. Two were from the 15 mg upadacitinib group, 3 from the 30 mg upadacitinib group, and 1 from the methotrexate group.
Excluding the difference in rate of side effects, the 30 mg dose of upadacitinib provided minimal additional benefit compared with the 15 mg dose.
van Vallenhoven R, Takeuchi T, Pangan AL, et al. Efficacy and safety of upadacitinib monotherapy in methotrexate-naïve patients with moderately to severely active rheumatoid arthritis (SELECT-EARLY): A randomized, double-blind, active-comparator, multi-center, multi-country trial. Arthritis Rheum. July 8 2020. doi:10.1002/art.41384