Long-term results of therapy with sequential use of rituximab and belimumab in patients with systemic lupus erythematosus

Abstract

Objective: To evaluate the efficacy of combination therapy with rituximab (RTM) and belimumab (BLM) in patients with systemic lupus erythematosus (SLE) during long-term follow-up. Material and methods. Twelve patients with definite high- and moderate activity SLE were included in the study. Nine of them had skin and joint manifestations, and the others had renal, peripheral nervous system involvement, and vasculitis. Patients received RTM at a dose of 500–2000 mg with premedication with 6-methylprednisolone and then BLM according to the standard regimen of 10 mg/kg once a month. Patients were divided into two groups according to the timing of assessment of long-term outcomes. In the 1st group, data were evaluated after 7–9 years (n = 4), and in the 2nd group – after 2–4 years (n = 8) after the prescription of biologic disease-modifying antirheumatic drugs (bDMARDs). Efficacy and tolerability of therapy, SLE activity, and dose of oral glucocorticoids (GC) were evaluated. Results and discussion. Against the background of combination therapy, clinical and immunological response was achieved in 11 of 12 patients after one year (median SLEDAI-2K at baseline – 10 [9.5; 14.5] points, 6 and 12 months after administratrion of BLM – 4 [2; 6] points). When bDMARDs were prescribed in the first two years of the disease, patients responded better to therapy and showed more significant positive dynamics in clinical and laboratory parameters. Subsequently, BLM therapy was limited to an average of 2 years, during which a stable remission was achieved. Prescribing bDMARDs allowed GC to be used as initial therapy in an exacerbation of SLE in medium and low doses (subsequently further reduced). Clinical remission was achieved and maintained in 7 patients, exacerbation at different time points after discontinuation of bDMARDs occurred in 3 patients, efficacy waned in one patient, and no result was achieved with combination therapy in another patient. Conclusion. The most pronounced positive result can be expected when a bDMARDs are prescribed as early as possible after diagnosis of SLE (in the first 2 years of the disease). It is advisable to administer BLM infusions as recommended once a month without long breaks between injections for at least 2 years and to continue until a durable effect is achieved. The use of low-dose GC and its discontinuation is an achievable goal, but careful monitoring of patients is needed to detect early symptoms of exacerbation.