Performance of leflunomide as a steroid-sparing agent in giant cell arteritis: A single-center, open-label study

Abstract

BackgroundThe management of giant cell arteritis (GCA) remains challenging and many patients require prolonged glucocorticoid treatment due to high disease relapse rates. We aimed to evaluate the role of leflunomide as a steroid-sparing agent in GCA.MethodsThis prospective open-label study included patients diagnosed with GCA between July 2014 and August 2020 and followed them for 96 weeks. At the time of diagnosis all patients received treatment following a predefined glucocorticoid regimen. At week 12 of follow-up, 10 mg of leflunomide per day was recommended as an adjunctive therapy. The decision to start with leflunomide treatment was patient-dependent. Follow-up visits were performed adhering to a predetermined protocol. The number of relapses, the cumulative glucocorticoid dose and treatment-related adverse events were recorded and compared between glucocorticoid-only and leflunomide groups.ResultsOf the 215 GCA patients [67.6% female, median (IQR) age 74 (66–79) years], 151 (70.2%) received leflunomide at week 12 (leflunomide group); the others continued with glucocorticoids (glucocorticoid-only group). During the study 64/215 (29.8%) patients relapsed. Of the 51 patients who relapsed after 12 weeks, 22/151 patients (14.6%) and 29/64 patients (45.3%) were in the leflunomide and glucocorticoid-only group, respectively (p = 0.001; NNT 3.3 for leflunomide). Furthermore, 80/151 patients in the leflunomide group managed to stop glucocorticoids at week 48 [with relapses in 6/80 patients (7.5%)]. The cumulative glucocorticoid dose was lower in the leflunomide group (p = 0.009).ConclusionIn our cohort, leflunomide safely and effectively reduced the GCA relapse rate and demonstrated a steroid-sparing effect in over three quarters of patients.

Treatment of Giant Cell Arteritis

“…The trial concluded that leflunomide was an effective steroid-sparing agent in three-quarters of patients and enabled a lower cumulative corticosteroid dose. 48 Other prospective observational series have also demonstrated the efficacy and safety of leflunomide as a steroid-sparing agent in GCA. 49…”

The spectrum of giant cell arteritis through a rheumatology lens

“…A metaanalysis of the methotrexate trials [70] demonstrated that use of methotrexate alongside glucocorticoids reduced relapses, cumulative glucocorticoid dose requirements, and increased the chance of sustained discontinuation of glucocorticoids, without any difference in adverse events between trial arms [70]. Other csDMARDs that have been utilised, but have not been adequately tested for efficacy in clinical trials, include leflunomide [71], azathioprine [72], and mycophenolate [73]. Cyclophosphamide is occasionally used for very severe or refractory cases, based on protocols developed in other types of vasculitis, but toxicity is high [74].…”

Giant cell arteritis: reviewing the advancing diagnostics and management

“…Leflunomide, another conventional synthetic DMARD suppresses the production of pro-inflammatory cytokines through the activation of dendritic cells and modifies the action of the T-cell response in GCA [126]. A number of studies support its use, but as of yet there is no randomised controlled evidence for its directed use [127][128][129][130].…”