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Current jakinibs for the treatment of rheumatoid arthritis: a systematic review

Cláudia Monfroni Rocha1, Alessandro Menna Alves2, Beatriz Fabris Bettanin1,2

  • 1Cell Culture Laboratory, Biotechnology Graduate Program, Universidade do Vale do Taquari, Univates, Av. Avelino Talini, 171, Lajeado, RS, 95914-014, Brazil.

Inflammopharmacology
|May 28, 2021
PubMed
Abstract

Insights

Janus kinase (JAK) inhibitors offer a new treatment option for severe rheumatoid arthritis (RA) patients who have not responded to other therapies. This review shows JAK inhibitors are effective and generally safe, though caution is advised for patients with severe liver or kidney disease.

Area of Science:

  • Rheumatology
  • Pharmacology
  • Immunology

Background:

  • Severe rheumatoid arthritis (RA) affects many patients unresponsive to conventional or biologic disease-modifying antirheumatic drugs (cDMARDs/bDMARDs).
  • A significant unmet need exists for effective and safe treatments in this patient population.
  • Small molecule Janus kinase (JAK) inhibitors represent a promising therapeutic class.

Purpose of the Study:

  • To systematically review the efficacy and safety of current JAK inhibitors (tofacitinib, peficitinib, decernotinib, upadacitinib, baricitinib, filgotinib).
  • To evaluate these JAK inhibitors in RA patients who failed prior cDMARD and/or bDMARD therapy.

Main Methods:

  • Systematic review of randomized controlled trials.
  • Searched major databases (Web of Science, Scopus, PubMed, clinicaltrials.gov) for relevant studies.
  • Keywords included 'rheumatoid arthritis', 'JAK inhibitor', and 'clinical trial'.

Main Results:

  • All evaluated JAK inhibitors demonstrated efficacy in ACR criteria (20, 50, 70) and Disease Activity Score 28 (DAS28) for low disease activity and remission.
  • Upadacitinib showed superior results compared to other JAK inhibitors in CRP-DAS28.
  • Tofacitinib achieved the best result in ESR-DAS28 for remission.
  • Peficitinib, baricitinib, and filgotinib had no reported deaths, while tofacitinib had 11 deaths.
  • Use in severe liver and kidney disease is not recommended.

Conclusions:

  • JAK inhibitors (e.g., tofacitinib, upadacitinib) are viable alternatives for moderate-to-severe RA, including in patients refractory to cDMARDs and bDMARDs.
  • JAK inhibitors can be used as monotherapy or in combination with methotrexate.
  • Further safety considerations are warranted, particularly in patients with comorbidities.
Keywords:
JAK inhibitorsRheumatoid arthritisSmall molecules

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