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A systematic review of clinical and preclinical evidences for Janus kinase inhibitors in large vessel vasculitis

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Abstract

Corticosteroid-sparing disease-modifying anti-rheumatic drugs are an area of active exploration in large vessel vasculitis (LVV), i.e., Takayasu arteritis (TAK) and Giant Cell Arteritis (GCA). The role of Janus kinase (JAK) inhibitors has been recently identified in different inflammatory rheumatic diseases. We conducted a systematic review of the use of JAK inhibitors in LVV across MEDLINE, Scopus, Web of Science, EMBASE, PubMed Central, Cochrane database of controlled trials, clinicaltrials.gov, and major recent international conferences. We identified four cohort studies and ten case reports. The JAK inhibitors used in these studies were tofacitinib, baricitinib, and ruxolitinib. A cohort study in TAK compared 27 patients treated with tofacitinib with 26 others treated with methotrexate, with better clinical outcomes with tofacitinib but similar angiographic stabilization, relapses, corticosteroid-sparing effect, and adverse events in both groups. Most of the other studies favored clinical responses with JAK inhibitors in LVV but with a paucity of data on other outcomes. Most of the included studies were of moderate quality. Evidence from pre-clinical models of LVV as well as limited in vivo data in patients with TAK appears to suggest that JAK inhibition reduces adventitial fibrosis, intimal proliferation, and inflammatory T lymphocyte infiltration in the media as well as reduces resident memory T cells in the vascular wall (which are otherwise resistant to corticosteroids). Ongoing clinical trials of tofacitinib, baricitinib, and upadacitinib in LVV shall help to further clarify the potential promise of JAK inhibitors for LVV (PROSPERO registration number CRD42021273359).

Key points

•Tofacitinib appeared to associate with better clinical outcomes than methotrexate in TAK.

•JAKinibs reduce adventitial fibrosis, intimal proliferation, and inflammatory vascular infiltrate in pre-clinical models of LVV.

•Tofacitinib downregulates resident memory vascular T lymphocytes in pre-clinical models of LVV.

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Data availability

All the analyses performed for this systematic review have been reported in the main text or in the supplementary files. Data pertaining to the systematic review shall be shared on reasonable request to the corresponding author (Durga Prasanna Misra, durgapmisra@gmail.com).

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Acknowledgements

Durga Prasanna Misra acknowledges support from Indian Council of Medical Research (Grant No 5/4/1-2/2019-NCD-II) for his research on Takayasu arteritis. The funding agency had no role in the actual conduct or reporting of this systematic review.

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Authors and Affiliations

  1. Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, 226014, India

    Upendra Rathore, Darpan Radheshyam Thakare, Vikas Agarwal & Durga Prasanna Misra

  2. School of Telemedicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, 226014, India

    Pallavi Patro

  3. Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India

    Aman Sharma

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  1. Upendra Rathore
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Contributions

The conception and design of the study—DPM, VA, AS.

Acquisition of data and analysis and interpretation of data—DPM, UR, DRT, PP.

Drafting the article—DPM, UR, DRT, PP.

Revising it critically for important intellectual content—VA, AS.

Final approval of the version to be submitted—DPM, UR, DRT, PP, VA, AS.

Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved—DPM, UR, DRT, PP, VA, AS.

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Correspondence to Durga Prasanna Misra.

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Rathore, U., Thakare, D.R., Patro, P. et al. A systematic review of clinical and preclinical evidences for Janus kinase inhibitors in large vessel vasculitis. Clin Rheumatol 41, 33–44 (2022). https://doi.org/10.1007/s10067-021-05973-4

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