Efficacy and safety of leflunomide versus cyclophosphamide for initial-onset Takayasu arteritis: a prospective cohort study

Abstract

Background: Leflunomide (LEF) has been considered as an alternative treatment for Takayasu arteritis (TA); however, data on its efficacy are still scanty. Objective: To investigate the efficacy and safety of LEF versus cyclophosphamide (CYC) for initial-onset TA. Methods: Initial-onset TA patients with active disease were enrolled in this research. Patients enrolled from 1 January 2009 to 31 December 2015 were treated with glucocorticoids and CYC, while patients enrolled from 1 January 2016 to 31 October 2018 received glucocorticoids and LEF. Treatment response including complete remission (CR), partial remission (PR), and effectiveness rate (ER) and side effects were evaluated at 6 and 12 months. Results and conclusion: In total, 92 patients were enrolled. A total of 47 patients were treated with LEF, while 45 patients were treated with CYC. The CR and ER rates were 75.55%, and 88.89% at 6 months, and 85.37% and 95.12% at 12 months in the LEF group. The CR and ER rates were 39.02% and 70.73% at 6 months, and 56.41% and 82.05% at 12 months in the CYC group. The CR rate was significantly higher in the LEF group than in the CYC group both at 6 months (75.61% versus 38.24%, p < 0.01) and 12 months (77.42% versus 53.33%, p < 0.05) after adjustment for propensity scores. The incidence of side effects in the LEF group was much lower than that in the CYC group (21.28% versus 44.44%). In conclusion, LEF provided a better treatment response, along with lower reproductive toxicity, compared with CYC in initial-onset TA.

Disease-modifying anti-rheumatic drugs for the management of Takayasu arteritis—a systematic review and meta-analysis

“…Ten observational studies evaluated cyclophosphamide in TAK [ 32 , 34 , 53 , 60 , 67 , 69 , 78 , 83 , 94 , 97 ], including three uncontrolled studies [ 32 , 34 , 53 ] where no direct comparison could be made with DMARDs. Pooled proportion of patients with at least partial clinical response was 48% (95% CI 27–69%, 2 studies, 23 patients, I 2 not assessable, Fig.…”

“…Six observational studies (and a seventh study, a longer-term follow-up of one of the previous ones) assessed leflunomide in TAK [ 42 , 57 , 82 , 83 , 93 , 94 , 99 ]. For the three uncontrolled observational studies, the pooled proportion of patients achieving at least a partial clinical response was 80% (95% CI 70–89%, 3 studies, 73 patients, I 2 not assessable, Fig.…”

“…The four studies comparing leflunomide with other DMARDs [ 57 , 83 , 93 , 94 ] shall be subsequently discussed.…”

“…Similar proportions of unmatched patients attained angiographic stabilization with cyclophosphamide or leflunomide (risk ratio for cyclophosphamide versus leflunomide at 6 months 0.88, 95% CI 0.74–1.05, and at 12 months 0.91, 95% CI 0.77–1.07). A higher risk of adverse events with cyclophosphamide was observed in the unmatched cohort (risk ratio for cyclophosphamide versus leflunomide 2.09, 95% CI 1.10–3.96)[ 94 ]. Although some of these confidence intervals for clinical response crossed 1, the magnitude of effect sizes favoured leflunomide over cyclophosphamide.…”

“…The remaining six studies comparing cyclophosphamide to other therapies shall be discussed subsequently [60,67,69,78,83,94].…”