2413: Janus Kinase Inhibitors in Giant Cell Arteritis in Clinical Practice. Real-World Clinical Practice Study and Literature Review

Fernando López¹, Javier Loricera², Toluwalase Tofade³, Diana Prieto-Peña², Susana Romero Yuste⁴, Eugenio De Miguel⁵, Anne Riveros-Frutos⁶, Ivan Ferraz Amaro⁷, Santos Castañeda⁸, Eztizen Labrador-Sánchez⁹, Olga Maiz¹⁰, Elena Becerra-Fernández¹¹, Javier Narvaez¹², Eva Galindez-Agirregoikoa¹³, Ismael González¹⁴, Ana Urruticoechea¹⁵, Sebastian Unizony¹⁶ and Ricardo Blanco¹⁷, ¹Rheumatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain, ²Hospital Universitario Marqués de Valdecilla, Santander, Spain, ³Neurology Department, Massachusetts General Hospital, Boston, MA, ⁴Complexo Hospitalario Universitario, Pontevedra, Spain, ⁵Hospital Universitario La Paz, Madrid, Spain, ⁶Hospital Universitario Germans Trias i Pujol, Barcelona, Spain, ⁷Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain, ⁸Hospital Universitario de la Princesa, Madrid, Spain, ⁹Hospital Universitario San Pedro, Laguardia, Spain, ¹⁰Hospital Universitario de Donostia. San Sebastián, Spain., Donosti, Spain, ¹¹Department of Rheumatology, Hospital Universitario de Torrevieja, London, United Kingdom, ¹²Hospital Universitario de Bellvitge, Barcelona, Spain, ¹³Basurto University Hospital, Bilbao, Spain, ¹⁴Hospital Universitario de León, León, Spain, ¹⁵Hospital Can Misses, Ibiza, Spain, ¹⁶Massachusetts General Hospital, Winchester, MA, ¹⁷Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain

Background/Purpose: Patients with giant cell arteritis (GCA) can relapse despite glucocorticoids, methotrexate and tocilizumab treatment. The JAK/STAT signalling pathway is involved in the pathogenesis of GCA, and JAK inhibitors (JAKi) are a potential treatment alternative. Baricitinib showed positive results in a small uncontrolled study (1).
The objective of this study is to evaluate the effectiveness of JAKi in GCA.

Methods: Real-world, retrospective clinical practice study of patients with GCA treated with JAKi. Outcomes assessed included disease relapse and safety. A literature search for other JAKi-treated GCA cases was conducted in PubMed, Embase and the Cochrane library from inception to 04/30/2023. We compared results of the previous baricitinib study (1) and the baricitinib recipients in our series.

Results: We present 34 patients (29 females[85%], mean age, 72.2 years, relapsing disease 34 [100%]) that received JAKi . The initial JAKi was baricitinib (n=14), tofacitinib (n=10) and upadacitinib (n=10) (Table and Figure). After a median [IQR] follow-up of 9.5 [4.2-12.7] months, 22 (64.7%) achieved and maintained remission, and 12 (35.3%) patients discontinued the initial JAKi due to relapse (n=10, 29.4%) or severe adverse events (SAEs) (n=2, 5.9%) including liver dysfunction and dyspnea/palpitations. The 12 patients failing the initial JAKi were switched to an alternative [JAKi (n=4), biologic therapy (n=7) and azathioprine (n=1)]. The literature review identified another 21 GCA patients (17 females, mean age 74.2 years) treated with JAKi, mostly with baricitinib (n=18). Most of these patients benefited from JAKi therapy (Table). Patients in our series receiving baricitinib had longer disease duration (median [IQR]31 [12-51] vs 9 [7-21] months; p=0.001) and had received biologics (71% vs 6.7%; p< 0.001) more frequently than those in the previous baricitinib study (1). Remaining baseline features were similar.

Conclusion: This real-world analysis suggest that JAKi could be effective in GCA, including patients failing other immunosuppressive therapies. The results of an ongoing phase 3 randomized controlled trial are awaited to confirm or rule out this observation.
References:

1. Koster MJ, et al. Ann Rheum Dis. 2022

F. López: None; J. Loricera: None; T. Tofade: None; D. Prieto-Peña: None; S. Romero Yuste: AbbVie, 6, AstraZeneca, 6, Biogen, 6, Lilly, 5, 6, Pfizer, 6, Sanofi, 1; E. De Miguel: None; A. Riveros-Frutos: None; I. Ferraz Amaro: AbbVie/Abbott, 5, 6, Amgen, 5, 6, Bristol-Myers Squibb(BMS), 6; S. Castañeda: None; E. Labrador-Sánchez: None; O. Maiz: None; E. Becerra-Fernández: None; J. Narvaez: None; E. Galindez-Agirregoikoa: None; I. González: None; A. Urruticoechea: None; S. Unizony: None; R. Blanco: AbbVie, 5, 6, Amgen, 6, AstraZeneca, 2, BMS, 6, Eli Lilly, 6, Galapagos, 2, 6, Janssen, 2, 6, MSD, 6, Novartis, 2, 6, Pfizer, 2, 6, Roche, 5, 6, Sanofi, 6.