Tofacitinib, Baricitinib, Upadacitinib, Filgotinib or Peficitinib? Study Compares Five Rheumatoid Arthritis Monotherapies

There are many existing medication options for patients with rheumatoid arthritis (RA), but which ones come out on top when it comes to safety and efficacy? Researchers recently compared five Janus kinase inhibitors (JAK inhibitors) to find the answer: tofacitinib, baricitinib, upadacitinib, filgotinib, and peficitinib.

“Several clinical trials have attempted to evaluate the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy in patients with active rheumatoid arthritis (RA), but their relative efficacy and safety as monotherapy remain unclear due to the lack of data from head‐to‐head comparison trials,” the study authors wrote.

They performed a Bayesian network meta-analysis combining direct and indirect evidence collected from randomized controlled trials (RCTs) to evaluate each medication’s safety and efficacy as monotherapy compared to placebo.

A total of five eligible RCTs were identified, encompassing 1,547 total eligible RA patients. Tofacitinib, baricitinib, upadacitinib, filgotinib, and peficitinib as monotherapy were all associated with a significantly higher American College of Rheumatology 20% (ACR20) response rate compared to placebo, with the highest ACR20 response rate observed in peficitinib 150 mg monotherapy (odds ratio=17.24.39; 95% credible interval, 6.57 to 51.80). Based on the surface under the cumulative ranking curve, the ranking probability portrayed that peficitinib 150 mg was correlated with the highest probability to be the best treatment in terms of ACR20 response rate achievement, followed by peficitinib 100 mg, filgotinib 200 mg, filgotinib 100 mg, tofacitinib 5 mg, upadacitinib 15 mg, baricitinib 4 mg and placebo. Rates of adverse events did not largely differ between the JAK inhibitor treatment groups, except tofacitinib 5 mg.

The study results were published in the Journal of Clinical Pharmacy and Therapeutics.

“All five JAK inhibitors—tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib—were efficacious monotherapy interventions for active RA, and differences were noted in their efficacy and safety in monotherapy,” the authors concluded.

Baricitinib made headlines recently when Eli Lilly announced the drug would be tested in patients with COVID-19.

Previous Tofacitinib vs. Upadacitinib Comparison

Previous comparisons have also been made between some of these JAK inhibitors, as well as versus placebo.

A 2019 study compared the safety and efficacy of tofacitinib and upadacitinib in patients with active RA who did not respond to conventional synthetic or biologic disease-modifying antirheumatic drugs (bDMARDs). The study concluded that upadacitinib was the more effective intervention and was not associated with significant safety risks.