Prevalence and predictors of flare after immunosuppressant discontinuation in patients with systemic lupus erythematosus in remission

Objectives. Patients with SLE are often exposed to prolonged immunosuppression since few data on flare recurrence in remitted patients who discontinued immunosuppressants are available. We aimed to assess the rate and predictors of flare after immunosuppressant withdrawal in SLE patients in remission. Methods. SLE patients diagnosed between 1990 and 2018 (according to the ACR criteria), ever treated with immunosuppressants and currently in follow-up were considered. Immunosuppressant discontinuation was defined as complete withdrawal of any immunosuppressive drug. Reasons for discontinuation were remission, defined as clinical SLEDAI-2K = 0 on a stable immunosuppressive and/or antimalarial therapy and/or on prednisone 5 mg/day, or poor adherence/intolerance. Flares were defined according to the SLEDAI Flare Index. Predictors of a subsequent flare were analysed by multivariate logistic regression. Results. There were 319 eligible patients out of 456 (69.9%). Of the 319 patients, 139 (43.5%) discontinued immunosuppressants, 105 (75.5%) due to remission, 34 (24.5%) due to poor adherence/intolerance. The mean (s.d.) follow-up time after immunosuppressant withdrawal was 91 (71) months (range 6-372). Among the patients who discontinued immunosuppressants, 26/105 remitted (24.7%) and 23/34 unremitted patients (67.6%) experienced a flare (P < 0.001) after a median (range) follow-up of 57 (6-264) and 8 months (1-72), respectively (P = 0.009). In patients who discontinued immunosuppressants due to remission, maintenance therapy with antimalarials (OR 0.243, 95% CI 0.070, 0.842) and the duration of remission at immunosuppressant discontinuation (OR 0.870, 0.824-0.996) were independent protective factors against disease flare. Conclusion. SLE flares are not uncommon after immunosuppressant discontinuation, even in remitted patients; however, antimalarial therapy and durable remission can significantly reduce the risk of flare.