Risk of hypogammaglobulinemia and rituximab

Rituximab, an anti-CD20-therapy that depletes B cells with high efficacy and tolerability, is used off-label for MS (in Sweden) [1]. From studies in rheumatology [2] and in other autoimmune diseases, such as neuromyelitis optica spectrum disorders [3], hypogammaglobulinemia is a well-known side effect associated with rituximab which can lead to treatment discontinuation and susceptibility for infections.

Dr Susanna Hallberg (Karolinska Institute, Sweden) and colleagues investigated the risk of developing decreased levels of IgG and IgM during long-term treatment with rituximab in MS patients (n=1,933). They found that the risk of hypogammaglobulinemia is an important side-effect in long-term treatment with rituximab in MS, which is consistent with previous findings in other autoimmune diseases [2,3].

The main predictors for treatment-induced Ig decrease were total accumulated dose of rituximab, treatment duration, and initial level of IgG. IgG levels decreased significantly in women during rituximab treatment. Furthermore, previous immune-modulatory treatment influenced initial IgG. Therefore, Dr Hallberg thinks that IgG and IgM levels should monitored regularly [4].

Finally, she suggested some treatment options for anti-CD20-induced hypogammaglobulinemia:

• Longer intervals or dose reduction of rituximab;
• Treatment discontinuation with clinical and MRI assessment, or consider other DMTs than anti-CD20 therapy;
• Regular follow up of patients with low IgG levels after cessation of rituximab [4].

Dr Hallberg advocated against using a continuous treatment in case of a trend towards lower levels of IgG. Intravenous Ig (IVIg) substitution is recommended in case of severe hypogammaglobulinemia (<4.0 g/L; or <6.7 mg/L in patients who are suspectable to infections). It is not known whether rituximab-induced hypogammaglobulinemia is reversible or not [4].

1. Granqvist M, et al. JAMA Neurol. 2018;75:320-327.
2. van Vollenhoven RF, et al. Ann Rheum Dis. 2013;72:1496-502.
3. Marcinnò A, et al. Neurol Neuroimmunol Neuroinflamm. 2018;5:e498.
4. Hallberg S, et al. ECTRIMS 2019, abstract 64.

Posted on 8 November 201916 February 2024