Long‐term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus

Abstract

on behalf of the LBSL02/99 Study GroupObjective. To evaluate the safety profile of longterm belimumab therapy combined with standard therapy for systemic lupus erythematosus (SLE) in patients with active disease.Methods. Patients who were randomized to receive intravenous placebo or belimumab 1, 4, or 10 mg/ kg, plus standard therapy, and completed the initial 52-week double-blind treatment period were then allowed to enter a 24-week open-label extension phase. During the extension period, patients in the belimumab group either received the same dose or were switched to 10 mg/kg and patients in the placebo group were switched to belimumab 10 mg/kg. Patients who achieved a satisfactory response during the 24-week extension period were allowed to participate in the long-term continuation study of monthly belimumab 10 mg/kg. Adverse events (AEs) and abnormal laboratory results were analyzed per 100 patient-years in 1-year intervals.Results. Of the 364 patients who completed the 52-week double-blind treatment period, 345 entered the 24-week extension, and 296 continued treatment with belimumab in the long-term continuation study. Safety data through 4 years of belimumab exposure (1,165 cumulative patient-years) are reported. Incidence rates of AEs, severe/serious AEs, infusion reactions, infections, malignancies, grades 3/4 laboratory abnormalities, and discontinuations due to AEs were stable or declined during 4-year belimumab exposure. The most common AEs included arthralgia, upper respiratory tract infection, headache, fatigue, and nausea. Serious infusion reactions were rare: only 1 occurred during the 4-year followup period. Rates of serious infection decreased from 5.9/100 patient-years to 3.4/100 patientyears, and no specific type of infection predominated.Conclusion. Belimumab added to standard therapy was generally well-tolerated over the 4-year treatment period in patients with SLE, which suggests that ClinicalTrials.gov identifiers: NCT00071487 and NCT00583362.

Belimumab in Systemic Lupus Erythematosus — What Can Be Learned from Longterm Observational Studies?

“…An acceptable safety profile has been reported from the same study population after 4 years of followup 15 , and the Ginzler study now with 7 years of followup did not reveal any evidently different patterns. Also, more analysis of nonresponders and reasons for treatment withdrawal could provide us with additional valuable information.…”

A case of central nervous system nocardiosis in a patient with lupus treated with belimumab

“…No cases of nocardiosis have ever been reported in patients with lupus on mycophenolate mofetil, hydroxychloroquine, or isoniazid. Moreover, nocardiosis has never been reported in patients on belimumab in safety studies or in post-market analysis (10). This is the first reported case regarding CNS nocardiosis in a patient treated with belimumab.…”

“…We will argue that belimumab or the combination because of the timing of symptom onset and the diagnosis of nocardiosis in relationship to belimumab exposure. According to safety data from the extension study, the cumulative rate of severe infections in patients who received mycophenolate with belimumab over 4 years was 1.5-fold greater than that in patients who received immunosuppressants other than mycophenolate with belimumab (9.4 vs. 6.3/100 patient-years) (10).…”

Upcoming biological therapies in systemic lupus erythematosus

“…In the BLISS-76 study, the belimumab 10 mg/kg group also met the primary efficacy end point at week 52 (SRI rate 43.2 vs 33.5% in placebo; p = 0.02) [17]. Both RTCs demonstrated a significant improvement in disease outcome with 10mg/kg of Belimumab when compared to placebo in terms of the cumulative risk of disease flares and time to first flare [17,18].…”