Clinical Trials Experience in GPA and MPA
Adverse reactions reported in ≥15% of Rituxan-treated patients were infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema (other important adverse reactions include infusion-related reactions).
Induction Treatment of Patients with Active GPA/MPA (GPA/MPA Study 1)
Infusion-Related Reactions: In GPA/MPA Study 1, 12% vs 11% (Rituxan-treated vs cyclophosphamide) of patients experienced at least one infusion-related reaction. Infusion-related reactions included cytokine release syndrome, flushing, throat irritation, and tremor. In the Rituxan group, the proportion of patients experiencing an infusion reaction was 12%, 5%, 4%, and 1% following the first, second, third, and fourth infusions, respectively. Patients were premedicated with antihistamine and acetaminophen before each Rituxan infusion and were on background oral corticosteroids, which may have mitigated or masked an infusion-related reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of infusion-related reactions.
Infections: In GPA/MPA Study 1, 62% vs 47% (Rituxan-treated vs cyclophosphamide-treated, respectively) of patients experienced an infection by Month 6. The most common infections in the Rituxan group were upper respiratory tract infections, urinary tract infections, and herpes zoster. The incidence of serious infections was 11% vs 10% (Rituxan-treated vs cyclophosphamide, respectively), with rates of approximately 25 and 28 per 100 patient-years, respectively. The most common serious infection was pneumonia.
Hypogammaglobulinemia: Hypogammaglobulinemia (IgA, IgG, or IgM below the lower limit of normal) has been observed in patients with GPA and MPA treated with Rituxan in GPA/MPA Study 1. At 6 months, in the Rituxan group, 27%, 58%, and 51% of patients with normal immunoglobulin levels at baseline had low IgA, IgG, and IgM levels, respectively, compared to 25%, 50%, and 46% in cyclophosphamide group.