Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids

Abstract

Objectives Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or class V LN. Methods We report the findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. Patients on maintenance steroids or with lifethreatening SLE or requiring dialysis were excluded. Renal remission was defined as serum creatinine no greater than 15% above baseline; complete biochemical remission (CR) was defined as urine protein : creatinine ratio (PCR)<50 mg/mmol or partial remission (PR) if PCR>50 mg/mmol but non-nephrotic and >50% reduction. Results A total of 45 (90%) patients achieved CR or PR by a median time of 37 weeks (range 4-200). Overall, 72% (n=36) achieved CR (median time 36 weeks (11-58)) and a further 18% (n=9) achieved persistent PR (median time 32 weeks (19-58)). By 52 weeks, CR and PR had been achieved in 52% (n=26) and 34% (n=17) respectively. In all, 12 relapses occurred in 11 patients, at a median time of 65.1 weeks (20-112) from remission. A total of 6/50 patients had systemic flares. Of the 45 responders, only 2 required >2 weeks of oral steroids. Adverse events were infrequent; 18% were admitted, 10% for an infective episode. Conclusions The rituxilup cohort demonstrates that oral steroids can be safely avoided in the treatment of LN. If findings are confirmed, it could mark a step change in the approach to the treatment of LN.

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

“…B cell–depletion therapy based on rituximab is as yet unlicensed for SLE, but is used to treat early‐onset and refractory disease 8, 9, 10, 11. However, the probability of and factors associated with the incidence of persistent hypogammaglobulinemia after rituximab in the routine clinical setting has not been explored.…”

B cells biology in systemic lupus erythematosus—from bench to bedside

“…Among other small sample open clinical trials, encouraging results of Rituximab, such as steroid-sparing effects and histological improvement in treating LN, were reported [163][164][165]. The negative results of EXPLORER and LUNAR trials may mainly due to the imperfect study design such as the enrollment criteria of baseline severity, evaluation tools and endpoints settings, instead of inefficiency.…”

Proliferative nephritis in childhood-onset systemic lupus erythematosus: current therapeutic approaches and future perspectives

“…One group has piloted the "steroid-avoiding rituxilup" protocol consisting of two doses of rituximab (1 g/dose) and intravenous methylprednisolone (500 mg) followed by maintenance therapy with MMF for the treatment of adults with LN 60 . Early reports have demonstrated that 72% of patients achieved complete response by a median time of 36 weeks, with 11 patients experiencing flare within a median time of 65 weeks.…”