Pragmatic treatment of patients with Systemic Lupus Erythematosus with rituximab: Long-term effects on serum immunoglobulins

Reddy V1,2, Martinez L2, Isenberg DA1,2, Leandro MJ1,2, Cambridge G1,2. Arthritis Care Res (Hoboken). 2016 Jul 18. doi: 10.1002/acr.22993. [Epub ahead of print]
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1Division of Rheumatology, University College London, Rayne Institute, 5 University St, London, UK. 2Hospital General Universitario, Gregorio Marañón, 28007, Madrid, Spain.


OBJECTIVE: B cell depletion therapy based on rituximab is a therapeutic option for refractory disease in patients with Systemic Lupus Erythematosus (SLE). The aim of this observational study was to document long-term effects on B cell function by following serum immunoglobulin levels in patients with SLE treated with rituximab in routine clinical practice.

METHODS: We included 57 consecutive patients with SLE treated with rituximab and concomitant/sequential immunosuppressants and measured serum total IgG, IgM, and IgA and IgG anti-dsDNA antibodies over a median of 48 months most recent follow-up. Flow cytometry was used prospectively to assess B-cell phenotypes in 17/57 patients.

RESULTS: Twelve patients (21%) had persistent IgM hypogammaglobulinemia (<0.4 g/L) and 3/55 (5%) had low IgG (<7g/L) at most recent follow-up (range 12-144 months). This was not associated with serious adverse events or high anti-dsDNA antibodies (>1000IU/ml; normal<50IU/ml). Factors predictive of low serum IgM included: baseline serum IgM ≤0.8g/L (receiver-operated-curve analysis) and subsequent therapy with mycophenolate mofetil (MMF) (odds ratio=6.8 compared with other immunosuppressants). In patients maintaining normal IgM levels (9/17), the frequency of circulating IgD+CD27+ B cells was significantly higher (p=0.05). At 12 months after rituximab, 7/30 SLE patients with baseline anti-dsDNA≤1000 IU/ml had lost seropositivity.

CONCLUSIONS: Lower baseline serum IgM levels and sequential therapy with MMF were predictive of IgM hypogammaglobulinemia after rituximab in SLE, but this was not associated with higher levels of anti-dsDNA antibodies or an increased risk of infections. This provides useful directions for clinicians regarding rituximab and sequential immunosuppressive treatment for patients with SLE.

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