JAK inhibitors: The game-changer for rheumatoid arthritis patients refractory to methotrexate

A recent study, PERFECTRA, has demonstrated that baricitinib, a Janus Kinase inhibitor (JAKi), is more effective than TNF inhibitors (TNFi) in treating patients with active rheumatoid arthritis (RA) who have not responded to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). This multicenter, real-life study provides new insights into treatment strategies for RA, highlighting the potential of baricitinib in a treat-to-target (T2T) setting.

The study involved 199 patients with RA who had disease durations of five years or less and had not been previously treated with biological or targeted synthetic DMARDs (b/tsDMARDs). These patients were randomized to receive either TNFi or baricitinib after failing to achieve disease control with csDMARDs. Over 48 weeks, changes in clinical measures and patient-reported outcome measures (PROMs) were assessed at 12-week intervals. The results showed that baricitinib was not only non-inferior but also superior to TNFi in achieving the ACR50 response at 12 weeks, with 42% of baricitinib patients reaching this milestone compared to 20% of TNFi patients. Additionally, 75% of patients on baricitinib achieved DAS28-CRP <2.6 at week 12, compared to 46% of those on TNFi. Throughout the study, baricitinib demonstrated comparable or better outcomes in secondary measures compared to TNFi.

Guidelines from both the European Alliance of Associations for Rheumatology and the American College of Rheumatology recommend using either a TNFi or a JAKi for patients with RA who do not achieve target disease activity with csDMARDs. Baricitinib, an oral selective JAK1/JAK2 inhibitor, is approved for use either as monotherapy or in combination with methotrexate for treating adults with moderate-to-severe active RA. This medication has shown significant improvements in clinical signs, symptoms, and patient-reported outcomes. Currently, baricitinib is approved for RA treatment in over 75 countries. In several pivotal phase II and III trials (RA-BALANCE, RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BEYOND), up to seven years of baricitinib treatment was well tolerated and provided rapid, sustained efficacy, a finding confirmed in real-world settings.

The PERFECTRA study suggests that for patients with RA who do not respond to csDMARDs, starting treatment with baricitinib is more effective than TNFi in achieving disease control and improving clinical outcomes. This finding could influence future treatment strategies, providing a more effective option for managing active rheumatoid arthritis in a T2T setting. With the ACR and EULAR guidelines recommending the use of JAKi for treatment of moderate to severe RA refractory to methotrexate monotherapy and the availability of long-term safety and efficacy data, it is anticipated that JAKiĀ  will revolutionize the prescription practices for rheumatic diseases.

References

  1. van de Laar CJ, Oude Voshaar MAH, Ten Klooster P, Tedjo DI, Bos R, Jansen T, et al. PERFECTRA: a pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs. RMD Open. 2024 May 30;10(2):e004291.
  2. Taylor PC, Laedermann C, Alten R, Feist E, Choy E, Haladyj E, et al. A JAK Inhibitor for Treatment of Rheumatoid Arthritis: The Baricitinib Experience. Journal of Clinical Medicine. 2023 Jan;12(13):4527.

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