medwireNews: Findings from a proof-of-concept trial provide preliminary evidence to suggest that the Janus kinase (JAK)1/2 inhibitor baricitinib is well tolerated and may have efficacy for the treatment of relapsing giant cell arteritis (GCA).
Outlining the rationale for their study, Matthew Koster (Mayo Clinic, Rochester, Minnesota, USA) and co-investigators explain that “tocilizumab is the only currently approved treatment for GCA by the US Food and Drug Administration (FDA) and the European Commission,” but the drug is not effective for all patients, highlighting the need for additional treatment options.
“[P]reclinical findings and preliminary case report responses demonstrate the biological plausibility that agents selectively targeting JAK1/JAK2 hold potential promise in GCA,” they add.
Before entering the phase 2 study, 15 patients (mean age 72 years, 73% women) with a median GCA duration of 9 months and a median of one prior relapse received tiered glucocorticoid (GC) treatment at a dose of 10–30 mg/day for 2–6 weeks. Once clinically stable for at least 2 weeks on their entry-level prednisone dose, all participants were given once-daily baricitinib 4 mg for 1 year alongside accelerated GC tapering, aiming to stop use by week 15–22.
All but one (93%) of the participants experienced at least one adverse event (AE), most frequently infections not requiring antibiotics (n=8), nausea (n=6), and infections requiring antibiotics (n=5).
“This frequency is similar to other clinical trials performed in patients with GCA, regardless of treatment or placebo arm,” and “[n]o new forms of treatment-emergent AEs [associated with baricitinib] were identified among this population,” note Koster and team.
They say that one participant experienced a serious AE during the study, specifically transient thrombocytopenia that was attributed to concomitant antiviral use. There were no cases of major cardiovascular events, venous thromboembolism, severe vascular symptoms, or gastrointestinal perforation.
In addition to its favorable safety profile, “[b]aricitinib at a dose of 4 mg/day appeared to have sufficient control over subsequent relapse both during accelerated GC tapering and also following GC discontinuation,” write the investigators in the Annals of the Rheumatic Diseases.
Indeed, just one (7%) participant experienced a flare during the study, and the remaining 13 patients included in the efficacy analysis achieved GC discontinuation and remained in remission at the 1-year follow-up. Median patient global assessment scores improved significantly from 20 points at baseline to 0 points at 24 weeks and 5 points at 1 year.
Koster and team caution that their proof-of-concept study evaluating the 4 mg/day dose of baricitinib was designed prior to the FDA approval of baricitinib 2 mg/day for rheumatoid arthritis, and that it is not known whether this lower dose would provide similar treatment responses in the GCA population.
They conclude: “Larger, double-blind, placebo-controlled studies are warranted to assess the utility of baricitinib in the management of patients with GCA.”
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