Adjunctive methotrexate for treatment of giant cell arteritis: An individual patient data meta‐analysis

Abstract

Objective. To reevaluate the efficacy and safety of adjunctive low-dose methotrexate (MTX) in giant cell arteritis (GCA).Methods. An individual patient data metaanalysis of 3 randomized placebo-controlled trials in patients with newly diagnosed GCA was performed. Treatment consisted of initial high-dose corticosteroids and randomly assigned oral MTX therapy (7.5-15 mg/ week) or placebo. Time-to-event outcomes were compared between groups using Cox proportional hazards models stratified by trial, and continuous outcomes were compared by calculating weighted mean differences.Results. The combined data set comprised 161 patients, of whom 84 received MTX and 77 received placebo. The mean duration of followup was 54.7 weeks (SD 39.2 weeks). Hazard ratios (HRs) for a first and second relapse of GCA were 0.65 (P ‫؍‬ 0.04) and 0.49 (P ‫؍‬ 0.02), respectively, in patients receiving MTX as compared with patients receiving placebo. Accordingly, a predicted 3.6 individuals (95% confidence interval [95% CI] 2.2-56.8) and 4.7 individuals (95% CI 3.3-21.9) need to be treated with MTX to prevent the occurrence of one first or one second relapse, respectively, up to 48 weeks. Use of MTX resulted in a reduction in the corticosteroid cumulative dose by 842 mg within 48 weeks (P < 0.001). Moreover, MTX treatment was associated with a higher probability of achieving sustained discontinuation of corticosteroids for >24 weeks (HR 2.84, P ‫؍‬ 0.001). Dropout rates and occurrence of adverse events did not differ between treatment groups.Conclusion. In GCA, adjunctive treatment with MTX lowers the risk of relapse and reduces exposure to corticosteroids. These findings indicate that MTX could be considered as a therapeutic option in addition to standard-of-care treatment with corticosteroids for patients with GCA.

Interleukin 6 Blockade as Steroid-sparing Treatment for 2 Patients with Giant Cell Arteritis: Figure 1.

“…For patients whose disease is resistant to or dependent on CS therapy, methotrexate (MTX) or azathioprine (AZA) is used as steroid-sparing second-line treatment, with conflicting results 3 . While MTX seems to be effective in controlling GCA 4,5 , the data on AZA remain controversial 6 ; the tumor necrosis factor-blocking agents infliximab and etanercept were not successful in inducing and maintaining disease remission 7,8 .…”

Translational Mini-Review Series on Immunology of Vascular Disease: Accelerated atherosclerosis in vasculitis

“…The disease occurs at younger age, particularly in women between 15 and 45 years, and is most frequent in Oriental, African and Latin American populations. GCA and Takayasu arteritis generally require steroid therapy for more than 1 year, often accompanied by other immunosuppressives such as methotrexate and/or azathioprine [21,22].…”

Incidence of infections in patients with giant cell arteritis: A cohort study

“…The burden of infection attributable to the use of high doses of steroids in GCA patients has not been well described in the literature. Case series have reported infection risks ranging from 15.8 -31% (12,13,22,23), but none had infections as their primary outcomes or compared the frequency of infection among GCA patients with that among a similar population without GCA. One controlled US study of 204 cases of GCA reported no increase in the incidence of herpes zoster, but did not include data about other infections (24).…”