Rituximab-Associated Infections
Section snippets
Overall Infectious Complications
The pivotal trial of rituximab in low-grade lymphoma administered four doses of 375 mg/m2 at weekly intervals to 166 patients with relapsed low-grade or follicular lymphoma, and showed profound depletion of B cells (usually to undetectable levels) that persisted for 6 to 12 months. Mean serum levels of IgG and IgA remained within the normal range and mean IgM levels decreased slightly below normal. Only 23 of 166 patients had significant reduction of their immunoglobulin levels. There were 68
Rituximab in Autoimmune Diseases: RA, SLE, Cryoglobulinemia, ITP, and Other Autoimmune Diseases
The standard dosing of rituximab in RA is 1,000 mg twice, administered 2 weeks apart. It may be given with weekly methotrexate, but the overall immunosuppression of these patients is generally lower than those receiving chemotherapy for hematologic malignancies. Perhaps for this reason, infections have been even less of an issue in trials for these conditions than in oncology. In the large randomized trials in RA,1, 2, 3, 4 serious infections were described in only 1% to 3% of patients. In the
Infections Associated With Rituximab Use in Solid Organ Transplantation
Rituximab was used originally in solid organ transplantation to prevent acute rejection in cases of HLA-sensitization102 or ABO-incompatible transplants,103, 104 or to treat acute humoral rejection.105 Several case series of rituximab use in highly sensitized patients have been published showing either no infections during relatively short follow-up periods106 or “no more infections than expected.”105, 107 However, a retrospective series of 34 patients documented increased number of infections
Potential Mechanisms of Increased Risk of Infections Associated With Rituximab
Of the multiple associations described in the preceding sections, the one better supported by evidence is the increased risk of infection with maintenance rituximab detected by meta-analyses.11, 12, 58 These seem to be non-opportunistic infections, and they could be explained by hypogammaglobulinemia and neutropenia, which are known to occur more frequently with more frequent administration of rituximab. Hypogammaglobulinemia is uncommon after rituximab therapy, but it was associated with
Summary and Recommendations
Rituximab has proven remarkably safe over years of use in hundreds of thousands of patients. The more important infectious risks seem to be reactivation of hepatitis B and increased infections with repeated administration. In addition, data derived from the experience in oncology and solid organ transplantation support the notion that the administration of rituximab to patients with pre-existing immune defects (advanced HIV infection) or concomitant intense immunosuppression may result in
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