Giant cell arteritis (GCA) and Takayasu arteritis (TAK) constitute two different types of large vessel vasculitis (1). In the elderly, GCA is often localized to the temporal arteries. However, GCA may be more widespread than generally assumed including the arteries extending from the aortic arch (2). Aortitis without the inclusion of the temporal arteries may also occur. Temporal artery biopsy (TAB) is valuable for the diagnosis of GCA and was included in the 1990 American College of Rheumatology (ACR) classification criteria (3). More recent diagnostic tools, including ultrasound (US) and computed tomography (CT) with or without the addition of positron emission tomography (PET), have improved diagnostic performance (4).

Immunomechanistic studies of GCA and TAK have revealed that dendritic cells in the arterial wall attract T cells and macrophages, and subsequently, granulomatous inflammation is formed. Several cytokines are involved in this process, for example, interleukin (IL)-6, IL-17, TNF, and interferon (IFN)-γ (5, 6). In 2017, tocilizumab (TCZ; a humanized monoclonal antibody targeting the IL-6 receptor) proved to be efficient in a randomized controlled trial (RCT) of GCA (7). Nonetheless, potentially dangerous, IL-6-blocking regimens also diminish or abolish the increase of C-reactive protein (CRP) in cases with serious infections (8–11). Patients with GCA are often old and could have multiple comorbidities combined with increased susceptibility to infection, which may hamper the enthusiasm of using IL-6-blocking therapy.

Many cytokines bind to extracellular receptors. Intracellularly, the pro-inflammatory signal of IL-6 and many other cytokines is mediated by the Janus kinase (JAK)/STAT pathway, and JAK–STAT signaling has proved important in both TAK and GCA (12–14). JAKs are subdivided into JAK1, JAK2, JAK3, and TYK2, and the effects of different cytokine receptors are mediated by pairs of these JAKs. The JAK inhibitor (JAKi) tofacitinib is considered a pan-JAKi and has shown signs of efficacy in TAK (15, 16). In 2022, Rathore et al. published a systematic review of cohort studies and case reports using JAKi in TAK or GCA (17).

The JAKi baricitinib is more selective to JAK1 and JAK2, and baricitinib has been studied in 15 GCA patients in a pilot study with promising results (18, 19). Furthermore, there are only a few case series or case reports describing the performance of baricitinib in GCA (20–22). One case of GCA treated with upadacitinib has been reported, and a randomized phase III study of upadacitinib in GCA is ongoing (SELECT-GCA) (ClinicalTrials.gov; NCT03725202) (23). In addition, one case of GCA treated with ruxolitinib has also been published (24).

By tradition, treatment of GCA starts with corticosteroids. High doses are effective, but in some patients, tapering the dose is difficult without getting a rebound of inflammation. In 2017, we started using baricitinib in a GCA patient with inadequate response to corticosteroids and where the abolishment of CRP reaction by TCZ in case of infection would have caused problems. Since then, we have treated other 14 GCA patients (who had failed on corticosteroids and/or TCZ, or where IL-6-blocking regimen with TCZ was considered inappropriate due to increased risk of, or impaired ability to diagnose, infections) with baricitinib or tofacitinib for ≥6 months, and the retrospective data of these patients are summarized herein.

This case series, including 15 Swedish individuals above the age of 60, provides an observational real-life experience of JAKi treatment in GCA for subjects where prednisolone alone was not sufficient or when the IL-6-blocking regimen was considered inappropriate. Our study population was highly selected since the subjects had failed on corticosteroids and that IL-6-blocking regimens such as TCZ were considered inappropriate due to a lack of CRP reaction in case of an infection. Still, the majority of the patients were able to decrease their daily corticosteroids significantly after the initiation of JAKi, and the beneficial effect remained over time. Although the prednisolone doses could be tapered, CRP values were stable or decreased, and the clinical status was improved or stable for all patients.

Overall, and as indicated in Table 2 , JAKi was well tolerated in the 15 subjects who remained on JAKi for ≥6 months. The clinical efficacy of JAKi herein appeared to be similar to that reported by Koster et al. in their 52-week proof-of-concept study using baricitinib 4 mg/day for patients with relapsing GCA (19). We observed no additional safety issues.

Assessment of inflammatory activity in GCA is not always straightforward. US as well as CT and PET-CT can support the evaluation but must be combined with laboratory and clinical data. Especially in the elderly, concomitant diseases may indeed blur the clinical picture, as illustrated by the cases with Aspergillus infection starting subclinically before JAKi initiation and by the dropouts where concurrent comorbidities, such as gout, confounded the evaluation of the clinical efficacy.

Aside from the two serious infections described, pulmonary embolism was observed in one patient suffering from several comorbidities after only 2 months of exposure to baricitinib. Obviously, causality between JAKi and pulmonary embolism in this patient cannot be excluded. Increased incidence of venous thrombosis and pulmonary embolism has indeed been reported in patients with rheumatoid arthritis (RA) treated with JAKi, both by the Food and Drug Administration’s adverse event reporting system and the Swedish Rheumatology Quality registers (26, 27). With regard to other adverse events and despite careful follow-up, we observed surprisingly few side effects considering that most of our patients were monitored for more than 1 year. Experience from JAKi studies on RA indicates an association with lipid profile alterations, including both high-density and low-density lipoproteins (28, 29). However, among our 15 patients, this was not observed during follow-up.

This case series must be interpreted in the context of its limitations, e.g., the absence of relevant controls. In addition, the retrospective design of the study limits the possibility to draw firm conclusions regarding efficacy. However, given the fact that the participants had failed on corticosteroids and were judged inappropriate for TCZ, relevant comparators were impossible to find. In the RCT for TCZ in the Giant Cell Arteritis trial (GiACTA), the median daily prednisolone dose in the placebo group that underwent the 26-week steroid tapering was approximately 18 mg compared with 8 mg in our study population. However, this is indeed not a perfect comparator group, especially since the same placebo group in GiACTA had a GCA duration of 365 days compared with 804 days in our study.

Safety is important but particularly challenging in the elderly population. As a reflection of this, in TCZ in GiACTA, adverse events were observed in more than 95% of the participants both in the treatment and placebo study arms (7). Another limitation of the current case series is the lack of a systematic follow-up with US or other imaging techniques. At least in arteries with a larger size than the temporal arteries, US could have given valuable information regarding the temporal development of inflammatory activity in GCA. In contrast, a major strength is the Swedish healthcare system, which is public and tax-funded and offers universal access. This significantly reduces the risk of selection bias and ensures a very high coverage of cases. Furthermore, in Sweden, existing drugs are allowed to be used off-label which is not the case for all countries.

To conclude, in line with the pilot study by Koster et al. and several independent observations, we report the encouraging efficacy data of JAKi in GCA (17, 19). The safety was comparable with prior reports in GCA. In the absence of published randomized controlled trials, clinical experience regarding efficacy and safety is important to convey to colleagues. This is one of the hitherto largest case series of JAKi in GCA with longer follow-up compared with existing reports. The clinical experiences of efficacy and safety reported by Koster et al. and us will complement the results from the awaited RCT and indicate that JAKi could be a therapeutic option in subjects with multiple comorbidities where high doses of corticosteroids and/or TCZ are considered inappropriate.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

PE: original idea, patient characterization, manuscript writing, and supervision. OS: patient characterization, manuscript writing, and statistics. CH: patient characterization and manuscript writing. CS: patient characterization, manuscript writing, and supervision. All authors reviewed the manuscript and approved the final version.