Clinical experience and safety of Janus kinase inhibitors in giant cell arteritis: a retrospective case series from Sweden

Abstract

The Janus kinase (JAK)–STAT signaling pathway is relevant in both Takayasu and giant cell arteritis (GCA), and the use of JAK inhibitors (JAKi) in arthritis, psoriasis, and inflammatory bowel disease is nowadays common. Some evidence of the clinical efficacy of JAKi in GCA exists and a phase III randomized controlled trial (RCT) of upadacitinib is currently recruiting. In 2017, we started using barcitinib in a GCA patient with inadequate response to corticosteroids, and later on, we treated other 14 GCA patients with baricitinib/tofacitinib during intense follow-up. The retrospective data of these 15 individuals are here summarized. GCA was diagnosed based on the ACR criteria and/or imaging techniques combined with increased C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) followed by a good initial response to corticosteroids. JAKi was initiated based on inflammatory activity, with increased CRP, presumably dependent on GCA with clinical symptoms, despite unsatisfying high doses of prednisolone. The mean age at JAKi initiation was 70.1 years and the mean exposure to JAKi was 19 months. From initiation, significant reductions in CRP were seen already at 3 (p = 0.02) and 6 (p = 0.02) months. A slower decrease was observed regarding ESR at 3 (p = 0.12) and 6 (p = 0.02) months. Furthermore, the daily prednisolone doses were reduced at 3 (p = 0.02) and 6 (p = 0.004) months. No GCA relapses were observed. Two patients were affected by serious infections, but JAKi therapy was retained or reintroduced after recovery. We present encouraging observational data on JAKi in GCA in one of the hitherto largest case series with long-term follow-up. Our clinical experiences will complement the results from the awaited RCT.

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

“…Moreover, to our knowledge, this is the largest study to date evaluating outcomes of GCA patients treated with JAKi. As such, our results expand prior findings [ 15 , 16 ], which have been mostly limited to patients naïve to treatment with conventional synthetic immunosuppressants and biologics, suggesting that JAKi can be useful in patients failing those therapies as well.…”

“…In our series, approximately one third of the patients relapsed while on JAKi and, despite a significant reduction in the daily prednisone dose by the end of follow up, only 20% stopped prednisone completely during the observation period. Possible explanations between our results and the results from the study by Eriksson et al [ 16 ] may include the fact that our cohort of patients could have had more refractory disease reflected by the fact that 63% failed conventional synthetic immunosuppressive agents and 86% failed biological therapy before JAKi initiation. A comparison between our study and the one by Koster et al [ 15 ] is challenging given the markedly different study designs (i.e., retrospective versus prospective), but factors determining what seems to have been an encouraging, yet poorer response to JAKi in our series may also comprise more recalcitrant disease in our cases demonstrated by longer disease duration, and again reflected in the higher exposures to first and second line therapies before JAKi treatment.…”

“…Clinical data on the efficacy and safety of JAKi in GCA are scarce and limited to a few cases reports, one small retrospective case series, and one small prospective study (Supplementary Table 2 ) [ 15 – 20 ]. Eriksson et al [ 16 ], evaluated the effectiveness and safety of baricitinib and tofacitinib in 15 relapsing patients with GCA and observed no further relapses, reduction in prednisone use, and improvement in CRP and ESR values during the observation period. Of note, only 20% of these patients had previously received conventional synthetic immunosuppressants and 20% had previously received biologics.…”

“…No cases of thromboembolism, stroke, myocardial infarction, significant cytopenias, or GCA-related permanent vision loss were observed. Adverse events reported in the study of Eriksson at al [ 16 ]. included a case of Aspergillus fumigatus infection and a case Enterococcus faecalis bacteremia.…”

Current Perspectives in Giant Cell Arteritis: Can We Better Connect Pathogenesis and Treatment?

“…For the moment, multiple promising molecules are in phase II and III studies (Table 3). The effect of Janus kinase (JAK) inhibitors, namely, tofacitinib (JAK1 and JAK3 inhibitors) and baricitinib (JAK1 and JAK2 inhibitors) [16] has been assessed in small pilot studies (less than 20 patients), and they seem to be well tolerated, but larger cohort trials are needed to evaluate the GC-sparing potential of this drug class [85]. Upadacitinib (a second-generation selective JAK1 inhibitor) is currently under evaluation in a phase III trial called SELECT-GCA, which plans to enroll more than 400 patients with active GCA [86].…”