OP0164 LEFLUNOMIDE IN COMBINATION WITH GLUCOCORTICOIDS IS SUPERIOR TO CONVENTIONAL GLUCOCORTICOIDS MONOTHERAPY IN PREVENTING RELAPSE IN IGG4-RELATED DISEASE: A RANDOMIZED, OPEN-LABEL, CONTROLLED TRIAL

Background Glucocorticoids (GCs) was recommended as first-line therapy for the induction of remission of IgG4-related disease (IgG4-RD), whereas, a large proportion of patients may fail to maintain remission with GCs monotherapy. Considering that recurrent flares might lead to irreversible organ damage, immunosuppressive agents should be added. However, opinions among the experts were split on this issue [1]. Previously, we preliminarily reported the efficacy and safety of GCs and leflunomide (LEF) combination therapy for maintaining the remission of IgG4-RD [2]. Objectives To evaluate the efficacy and safety of GCs and LEF combination therapy compared with GCs monotherapy for the management of IgG4-RD. Methods This study was a 12-month, randomized, open-label, controlled trial (NCT02703194). Patients were randomly allocated to GCs and LEF combination therapy or GCs monotherapy with 1:1 group allocation ratio. The dosage of LEF was 20 mg/d. All received GCs with a predefined taper regimen from a starting dosage of 0.5-0.8mg/kg/d. The primary outcome was time to relapse and the main secondary outcomes were time to complete response (CR) and time to remission. Results A total of 66 patients were randomly assigned (33 in each group) (Figure 1). The demographic and disease characteristics of the patients in the ITT population were similar between the treatment groups. The mean initial dosages of GCs were similar (GCs and LEF: 0.68 mg/kg/d, GCs: 0.70mg/kg/d, P=0.529). The cumulative relapse rates at 12 months were 21.2% in the GCs and LEF group and 50.0% in the GCs group (P=0.023). GCs and LEF combination therapy was significantly superior to GCs monotherapy with respect to the time to relapse (HR, 0.35; 95% CI, 0.13 to 0.90; P=0.030) (Figure 2), and was superior to GCs monotherapy with respect to the time to remission (HR, 1.74 95% CI, 0.97 to 3.10; P=0.063). These two groups were similar when analyzing the time to CR (HR, 1.57 95% CI, 0.91 to 2.74; P=0.108). At 12 months, 14 (42.4%) patients in the GCs group and 22 (66.7%) patients in the GCs and LEF group successfully tapered GCs to 10 mg/d or less with no relapse (P=0.048), 6 (18.2%) patients in the GCs group and 18 (54.5%) patients in the GCs and LEF group to 5 mg/d or less with no relapse (P=0.002). The relapsing organs of these relapsing patients were salivary glands (n=5), pancreas (n=5), bile ducts (n=5), retroperitoneal fibrosis (n=3), lacrimal gland (n=1), and skin (n=1). The incidences of new-onset diabetes mellitus (GCs and LEF: 21.21%, GCs: 27.27%, P=0.566) and the infections (GCs and LEF: 18.18%, GCs: 12.12%, P=0.566) were similar between two treatment groups. Conclusion The efficacy of LEF in combination with GCs therapy was significantly superior to conventional GCs monotherapy in preventing relapse in patients with IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD. References [1] Khosroshahi A, Wallace ZS, Crowe JL, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol. 2015 67: 1688-99. [2] Wang Y, Li K, Gao D, et al. Combination therapy of leflunomide and glucocorticoids for the maintenance of remission in patients with IgG4-related disease: a retrospective study and literature review. Intern Med J2017; 47: 680-9. Disclosure of Interests None declared