Effectiveness of janus kinase inhibitors in relapsing giant cell arteritis in real-world clinical practice and review of the literature

• Published in: Arthritis research & therapy Vol. 26; no. 1; pp. 116 - 10
• Main Authors: Loricera, Javier, Tofade, Toluwalase, Prieto-Peña, Diana, Romero-Yuste, Susana, de Miguel, Eugenio, Riveros-Frutos, Anne, Ferraz-Amaro, Iván, Labrador, Eztizen, Maiz, Olga, Becerra, Elena, Narváez, Javier, Galíndez-Agirregoikoa, Eva, González-Fernández, Ismael, Urruticoechea-Arana, Ana, Ramos-Calvo, Ángel, López-Gutiérrez, Fernando, Castañeda, Santos, Unizony, Sebastian, Blanco, Ricardo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05-06-2024; BioMed Central; BMC
• Subjects: Aged; Aged, 80 and over; Azetidines - therapeutic use; Baricitinib; Diagnosis; Diseases; Drug therapy; Drugs; Female; Giant cell arteritis; Giant Cell Arteritis - blood; Giant Cell Arteritis - drug therapy; Health aspects; Heterocyclic Compounds, 3-Ring; Humans; Janus kinase inhibitors; Janus Kinase Inhibitors - therapeutic use; Large vessel vasculitis; Male; Middle Aged; Patient outcomes; Piperidines - therapeutic use; Purines - therapeutic use; Pyrazoles - therapeutic use; Pyrimidines - therapeutic use; Recurrence; Relapse; Retrospective Studies; Sulfonamides - therapeutic use; Tofacitinib; Treatment Outcome; Upadacitinib; Spain; Large vessel vasculitis; Giant cell arteritis; Tofacitinib; Upadacitinib; Janus kinase inhibitors; Baricitinib
• ISSN: 1478-6354; 1478-6362; 1478-6362
• DOI: 10.1186/s13075-024-03314-9

A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature.
Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted.
Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them.
This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).