Upadacitinib Compared to Tofacitinib for Active RA

A recent study published in International Journal of Rheumatic Diseases compared the safety and efficacy of tofacitinib and upadacitinib in patients with active rheumatoid arthritis (RA) who did not respond to conventional synthetic (cs) or biologic (b) disease-modifying antirheumatic drugs (DMARDs). The study concluded that upadacitinib was the more effective intervention and was not associated with significant safety risks.

The study was conducted using a Bayesian network meta-analysis of direct and indirect evidence from randomized controlled trials (RCTs). RCTs eligible for inclusion assessed the efficacy and safety of tofacitinib and upadacitinib in combination with methotrexate in patients with previous failure using csDMARDs or bDMARDs.

Upadacitinib Comes Out on Top for Efficacy

Final analysis included nine RCTs encompassing a total of 5,794 patients. The studies yielded 15 pairwise comparisons that included 10 direct comparisons of six interventions. Upadacitinib 15 mg plus methotrexate and upadacitinib 30 mg plus methotrexate were considered the most effective treatment modalities, followed by tofacitinib 10 mg plus methotrexate, tofacitinib 5 mg plus methotrexate, and adalimumab plus methotrexate.

The researchers further observed: “Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX and upadacitinib 30 mg + MTX had the highest probability of being the best treatment in terms of the American College of Rheumatology 20 response rate (SUCRA = 0.820, 0.762), followed by tofacitinib 10 mg + MTX (SUCRA = 0.623), tofacitinib 5 mg + MTX (SUCRA = 0.424), adalimumab + MTX (SUCRA = 0.371), and placebo + MTX (SUCRA = 0.001).”

Serious adverse event rates were not significantly different among upadacitinib plus methotrexate, tofacitinib plus methotrexate, adalimumab plus methotrexate, and placebo plus methotrexate treatments.

Past Research: Upadacitinib Beats Methotrexate, High-dose Tofacitinib Comes with Warnings

Another recent study, published in The Lancet, found that patients with inadequate response to methotrexate may have improved clinical and functional outcomes with upadacitinib monotherapy as opposed to continuing methotrexate. A total of 598 randomized patients completed the trial, which measured 20% improvement in ACR criteria (ACR20) and low disease activity (28-joint Disease Activity Score using C-reactive protein [DAS28{CRP}] of 3.2 or lower) achievement. After 14 weeks, ACR20 was achieved by 41% of the methotrexate group, 68% of the upadacitinib 15 mg group, and 71% of the upadacitinib 30 mg group. DAS28(CRP) of 3.2 or lower was attained in 19% of the methotrexate group, 45% of the upadacitinib 15 mg group, and 53% of the upadacitinib 30 mg group.

Earlier this year, the Food and Drug Administration issued a warning pertaining to the use of high-dose tofacitinib to treat RA, associating it with an increased risk of blood clots in the lungs and death. Tofacitinib is FDA approved for the treatment of RA—but only in a 5 mg twice daily dose; the 10 mg twice daily dose is only approved for the treatment of ulcerative colitis.