Baricitinib for Relapsing Giant Cell Arteritis: a Prospective Open-label 52-week Pilot Study

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 2022 Feb 22

PMID 35190385

Authors

Matthew J Koster

Cynthia S Crowson

Rachel E Giblon

Jane M Jaquith

Ali Duarte-Garcia

Eric L Matteson

Cornelia M Weyand

Kenneth J Warrington

Affiliations

Soon will be listed here.

Abstract

Background/purpose: Preclinical vascular inflammation models have demonstrated effective suppression of arterial wall lesional T cells through inhibition of Janus kinase 3 and JAK1. However, JAK inhibition in patients with giant cell arteritis (GCA) has not been prospectively investigated.

Methods: We performed a prospective, open-label, pilot study of baricitinib (4 mg/day) with a tiered glucocorticoid (GC) entry and accelerated taper in patients with relapsing GCA.

Results: 15 patients were enrolled (11, 73% female) with a mean age at entry of 72.4 (SD 7.2) years, median duration of GCA of 9 (IQR 7-21) months and median of 1 (1-2) prior relapse. Four (27%) patients entered the study on prednisone 30 mg/day, 6 (40%) at 20 mg/day and 5 (33%) at 10 mg/day. Fourteen patients completed 52 weeks of baricitinib. At week 52, 14/15 (93%) patients had ≥1 adverse event (AE) with the most frequent events, including infection not requiring antibiotics (n=8), infection requiring antibiotics (n=5), nausea (n=6), leg swelling (n=2), fatigue (n=2) and diarrhoea (n=1). One subject required baricitinib discontinuation due to AE. One serious adverse event was recorded. Only 1 of 14 (7%) patients relapsed during the study. The remaining 13 patients achieved steroid discontinuation and remained in disease remission during the 52-week study duration.

Conclusion: In this proof-of-concept study, baricitinib at 4 mg/day was well tolerated and discontinuation of GC was allowed in most patients with relapsing GCA. Larger randomised clinical trials are needed to determine the utility of JAK inhibition in GCA.

Trial Registration Number: NCT03026504.

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References

Adler S, Reichenbach S, Gloor A, Yerly D, Cullmann J, Villiger P . Risk of relapse after discontinuation of tocilizumab therapy in giant cell arteritis. Rheumatology (Oxford). 2019; 58(9):1639-1643. DOI: 10.1093/rheumatology/kez091. View

Regent A, Terrier B, Legendre P, Wartski M, Cohen P, Mouthon L . Efficacy of baricitinib for refractory large-vessel vasculitis. Rheumatology (Oxford). 2021; 60(11):e389-e391. DOI: 10.1093/rheumatology/keab541. View

Alba M, Garcia-Martinez A, Prieto-Gonzalez S, Tavera-Bahillo I, Corbera-Bellalta M, Planas-Rigol E . Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients. Medicine (Baltimore). 2014; 93(5):194-201. PMC: 4602452. DOI: 10.1097/MD.0000000000000033. View

Taylor P, Weinblatt M, Burmester G, Rooney T, Witt S, Walls C . Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis. Arthritis Rheumatol. 2019; 71(7):1042-1055. PMC: 6618316. DOI: 10.1002/art.40841. View

Taylor P, Keystone E, van der Heijde D, Weinblatt M, Del Carmen Morales L, Reyes Gonzaga J . Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017; 376(7):652-662. DOI: 10.1056/NEJMoa1608345. View

Rathore U, Thakare D, Patro P, Agarwal V, Sharma A, Misra D . A systematic review of clinical and preclinical evidences for Janus kinase inhibitors in large vessel vasculitis. Clin Rheumatol. 2021; 41(1):33-44. DOI: 10.1007/s10067-021-05973-4. View

Hoffman G, Cid M, Hellmann D, Guillevin L, Stone J, Schousboe J . A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum. 2002; 46(5):1309-18. DOI: 10.1002/art.10262. View

Langford C, Cuthbertson D, Ytterberg S, Khalidi N, Monach P, Carette S . A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. Arthritis Rheumatol. 2017; 69(4):837-845. PMC: 5378642. DOI: 10.1002/art.40044. View

Zhang H, Watanabe R, Berry G, Tian L, Goronzy J, Weyand C . Inhibition of JAK-STAT Signaling Suppresses Pathogenic Immune Responses in Medium and Large Vessel Vasculitis. Circulation. 2017; 137(18):1934-1948. PMC: 5930040. DOI: 10.1161/CIRCULATIONAHA.117.030423. View

10.

Stone J, Han J, Aringer M, Blockmans D, Brouwer E, Cid M . Long-term effect of tocilizumab in patients with giant cell arteritis: open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial. Lancet Rheumatol. 2024; 3(5):e328-e336. DOI: 10.1016/S2665-9913(21)00038-2. View

11.

Genovese M, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L . Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med. 2016; 374(13):1243-52. DOI: 10.1056/NEJMoa1507247. View

12.

Hoffman G, Cid M, Rendt-Zagar K, Merkel P, Weyand C, Stone J . Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial. Ann Intern Med. 2007; 146(9):621-30. DOI: 10.7326/0003-4819-146-9-200705010-00004. View

13.

Keystone E, Taylor P, Drescher E, Schlichting D, Beattie S, Berclaz P . Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis. 2014; 74(2):333-40. PMC: 4316868. DOI: 10.1136/annrheumdis-2014-206478. View

14.

Crowson C, Matteson E, Myasoedova E, Michet C, Ernste F, Warrington K . The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis Rheum. 2011; 63(3):633-9. PMC: 3078757. DOI: 10.1002/art.30155. View

15.

Hunder G . The early history of giant cell arteritis and polymyalgia rheumatica: first descriptions to 1970. Mayo Clin Proc. 2006; 81(8):1071-83. DOI: 10.4065/81.8.1071. View

16.

Spiera R, Paget S, Spiera H . Methotrexate in giant-cell arteritis. Ann Intern Med. 2001; 135(11):1006-7. DOI: 10.7326/0003-4819-135-11-200112040-00018. View

17.

Kermani T, Warrington K, Cuthbertson D, Carette S, Hoffman G, Khalidi N . Disease Relapses among Patients with Giant Cell Arteritis: A Prospective, Longitudinal Cohort Study. J Rheumatol. 2015; 42(7):1213-7. PMC: 4505815. DOI: 10.3899/jrheum.141347. View

18.

Villiger P, Adler S, Kuchen S, Wermelinger F, Dan D, Fiege V . Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2016; 387(10031):1921-7. DOI: 10.1016/S0140-6736(16)00560-2. View

19.

Fleischmann R, Takeuchi T, Schiff M, Schlichting D, Xie L, Issa M . Efficacy and Safety of Long-Term Baricitinib With and Without Methotrexate for the Treatment of Rheumatoid Arthritis: Experience With Baricitinib Monotherapy Continuation or After Switching From Methotrexate Monotherapy or Baricitinib Plus.... Arthritis Care Res (Hoboken). 2019; 72(8):1112-1121. DOI: 10.1002/acr.24007. View

20.

Stone J, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D . Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med. 2017; 377(4):317-328. DOI: 10.1056/NEJMoa1613849. View