JAK inhibitors and systemic sclerosis: A systematic review of the literature

Autoimmun Rev. 2022 Oct;21(10):103168. doi: 10.1016/j.autrev.2022.103168. Epub 2022 Aug 6.

Abstract

Background: Systemic sclerosis (SSc) is a systemic autoimmune disease with heterogeneous clinical presentation and prognosis. JAK inhibitors reduced cutaneous and pulmonary fibrosis in mice models of SSc. Clinical data regarding the efficacy and safety of JAK inhibitors in SSc patients are scarce.

Methods: We performed a systematic literature review of patients with SSc defined by the 2013 ACR/EULAR criteria and treated with JAK inhibitors, searching in Medline, Cochrane library and Embase databases.

Results: Fifty-nine patients (mean age 47 ± 15 years) were included. Median treatment duration was 12 [6-12] months. JAK inhibitors (tofacitinib in 47 patients and baricitinib in 12 patients) were prescribed as first line therapy in 35 patients (59%). A significant cutaneous response (decrease in the mRSS - modified Rodnan skin score - of >5 points and ≥ 25% from baseline) was reported in 52 patients (88%). Among patients with interstitial lung disease (ILD) (n = 31), 28/29 patients had no ILD progression during follow-up time (missing data in 2 patients). Only 2 patients had a disease progression during treatment (including one patient with progressive skin fibrosis). Cutaneous response was more frequently observed in treatment naïve SSc patients. Decrease of the mRSS after treatment initiation was more significant in treatment naïve SSc patients. Eighteen non-serious side-effects were noted in 12 patients (20%), without treatment interruption: 6 infections, 6 gastrointestinal disorders, 4 hepatitis and 3 dyslipidemias.

Conclusion: JAK inhibitors could represent a safe and effective treatment option for skin fibrosis and ILD in systemic sclerosis.

Keywords: Baracitinib; JAK inhibitors; Systemic sclerosis; Tofacitinib.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Fibrosis
  • Humans
  • Janus Kinase Inhibitors* / adverse effects
  • Lung Diseases, Interstitial* / drug therapy
  • Lung Diseases, Interstitial* / etiology
  • Mice
  • Scleroderma, Systemic* / drug therapy
  • Skin Diseases*

Substances

  • Janus Kinase Inhibitors