Clinical Trials Experience in RA
Among all exposed patients, adverse reactions reported in greater than 10% of patients include infusion reactions, upper respiratory tract infection, nasopharyngitis, urinary tract infection, and bronchitis.
In placebo-controlled studies, adverse reactions reported in ≥5% of patients were hypertension (8% vs 5%), nausea (8% vs 5%), upper respiratory tract infection (7% vs 6%), arthralgia (6% vs 4%), pyrexia (5% vs 2%), and pruritus (5% vs 1%) in Rituxan-treated vs placebo-treated patients, respectively.
Infusion Reactions: In the Rituxan RA pooled, placebo-controlled studies, incidence of any adverse event within 24 hours of an infusion was 32% vs 23% after the first infusion and 11% vs 13% after the second infusion in the Rituxan-treated patients and placebo group, respectively. Incidence of acute infusion reactions was 27% vs 19% after the first infusion and 9% vs 11% after the second infusion in the Rituxan-treated patients and placebo group, respectively. Serious acute infusion reactions were experienced by <1% of patients in either treatment group. Acute infusion reactions required dose modification (stopping, slowing, or interruption of the infusion) in 10% and 2% of patients receiving Rituxan or placebo, respectively, after the first course.
Infections: In the pooled, placebo-controlled studies, incidence of any type of infection was 39% vs 34%, Rituxan-treated vs placebo, respectively. The most common infections were nasopharyngitis, upper respiratory tract infections, urinary tract infections, bronchitis, and sinusitis. The incidence of serious infections was 2% vs 1%, Rituxan-treated vs placebo group, respectively.
In the experience with Rituxan in 2578 RA patients, the rate of serious infection was 4.31 per 100 patient-years. The most common serious infections (≥0.5%) were pneumonia or lower respiratory tract infections, cellulitis, and urinary tract infections. Fatal serious infections included pneumonia, sepsis, and colitis. Rates of serious infection remain stable in patients receiving subsequent courses.
In 185 Rituxan-treated RA patients with active disease, subsequent treatment with a biologic DMARD, the majority of which were TNF antagonists, did not appear to increase the rate of serious infection.
Cardiovascular Adverse Reactions: In the pooled, placebo-controlled studies, incidence of serious cardiovascular reactions was 1.7% vs 1.3%, Rituxan-treated vs placebo, respectively. Three cardiovascular deaths occurred during the double-blind period of the RA studies including all Rituxan regimens (3/769=0.4%) compared to none in the placebo treatment group (0/389). In the experience with Rituxan in 2578 RA patients, the rate of myocardial infarction (MI) was consistent with MI rates in the general RA population. Rituxan should be discontinued in the event of a serious or life-threatening cardiac event.
Hypophosphatemia and Hyperuricemia: In the pooled, placebo-controlled studies, newly occurring hypophosphatemia (<2.0 mg/dL) was 12% vs 10%, Rituxan-treated vs placebo, respectively. Hypophosphatemia was more common in patients who received corticosteroids. Newly occurring hyperuricemia (>10 mg/dL) was observed in 1.5% vs 0.3%, Rituxan-treated vs placebo, respectively.