B cell depletion therapy in systemic lupus erythematosus: long-term follow-up and predictors of response

Abstract

Objectives: To describe the long-term clinical outcome and safety profile of B cell depletion therapy (BCDT) in patients with systemic lupus erythematosus (SLE). It was also determined whether baseline parameters can predict the likelihood of disease flare. Methods: 32 patients with refractory SLE were treated with BCDT using a combination protocol (rituximab and cyclo-phosphamide). Patients were assessed with the British Isles Lupus Assessment Group (BILAG) activity index, and baseline serology was measured. Flare was defined as a new BILAG ‘A’ or two new subsequent ‘B’s in any organ system. Results: Of the 32 patients, 12 have remained well after one cycle of BCDT (median follow-up 39 months). BCDT was followed by a decrease of median global BILAG scores from 13 to 5 at 6 months (p = 0.006). Baseline anti-extractable nuclear antigen (ENA) was the only identified independent predictor of flare post-BCDT (p = 0.034, odds ratio = 8, 95% CI 1.2 to 55) from multivariable analysis. Patients with low baseline serum C3 had a shorter time to flare post-BCDT (p = 0.008). Four serious adverse events were observed. Conclusion: Autoantibody profiling may help identify patients who will have a more sustained response. Although the long-term safety profile of BCDT is favourable, ongoing vigilance is recommended.

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

“…In 15 of 40 patients (38%), anti‐dsDNA levels normalized, with the majority (13 of 15) having had levels ≤1,000 IU/ml at baseline (Figure 5D). No serious adverse events were observed 31, 33, and none of the patients required intravenous Ig therapy.…”

“…A typical rituximab treatment cycle consisted of rituximab, 2 doses of 1 gm given 1–2 weeks apart in combination with 1 dose of intravenous cyclophosphamide (750 mg). The clinical response to rituximab in this cohort has been reported previously 31. Clinical and laboratory parameters were analyzed during the first cycle of rituximab (up to 12 months) and the most recent time point from all patients, some of whom had received multiple cycles of rituximab‐based treatment in combination with concomitant and/or subsequent therapy with immunosuppressants to determine longer‐term effects on the recovery of B cell subpopulations, serum Ig, and autoantibodies.…”

“…Percentages of patients in each group were similar (7 of 12 [58%] in the low IgM group and 22 of 45 [49%] in the normal IgM group). Detailed patient demographics and clinical responses of this cohort of 57 patients have been previously described 31, 32, 33. The median age at the time of the first rituximab treatment cycle was 34 years (range 17–74 years).…”

Short-Term Effects of Rituximab in Children with Steroid- and Calcineurin-Dependent Nephrotic Syndrome

“…Rituximab was first introduced in clinical prac-tice for the treatment of non-Hodgkin's lymphoma and then extended to autoimmune diseases (12), such as rheumatoid arthritis (13), lupus erythematosus (14,15), vasculitic disorders (16), and membranous nephropathy (12,17,18). Recent uncontrolled studies suggest that RTX may maintain remission of INS as effectively as standard therapy based on prednisone and calcineurin inhibitors (19 -22).…”

Role of Rituximab Therapy in Glomerulonephritis

“…9 -11 More than 20 studies of almost 300 patients reported response rates averaging 75% in refractory lupus or lupus nephritis treated with rituximab (Table 1). [12][13][14][15][16] Responses are accompanied by falls in anti-double-stranded DNA antibodies, correction of complement depletion, and reduction in glucocorticoid requirement. Varying treatment protocols, response criteria, and positive reporting bias indicate caution is necessary in interpreting these results, compounded by the failure of the first randomized trial, EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus), to demonstrate a superior response to rituximab in addition to glucocorticoids for remission induction in nonrenal lupus.…”