In 938 patients from pooled pivotal trials, incidence of Rituxan adverse events ≥2% and at least 1% greater than placebo¹

Adverse Events

The most common adverse events with greater incidence in the group receiving Rituxan (n=540) vs the placebo group (n=398) 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%). These data are based on 938 patients treated in phase 2 and 3 studies of Rituxan (2 x 1000 mg) or placebo administered in combination with methotrexate.

Infusion Reactions: In RA studies, 32% of Rituxan patients experienced an adverse event during or within 24 hours following their first infusion, compared to 23% for placebo. This decreased to 11% and 13%, respectively following the second infusion. Acute infusion reactions (manifested by fever, chills, rigors, pruritus, urticaria/rash, angioedema, sneezing, throat irritation, cough, and/or bronchospasm, with or without associated hypotension or hypertension) were experienced by 27% of Rituxan patients following their first infusion, compared to 19% for placebo. These acute infusion reactions decreased to 9% and 11%, respectively. Serious acute infusion reactions were experienced by <1% of patients in either treatment group.

Infections: In RA clinical studies, 39% of patients in the Rituxan group experienced an infection of any type compared to 34% for placebo. The most common infections were nasopharyngitis, upper respiratory tract infections, urinary tract infections, bronchitis, and sinusitis.

The incidence of serious infections was 2% in the Rituxan patients and 1% in the placebo group. 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. 13 serious infections were observed in 186.1 patient-years (6.99 per 100 patient-years) prior to exposure and 10 were observed in 182.3 patient-years (5.49 per 100 patient-years) after exposure.

Cardiac Events: The incidence of serious cardiovascular events in the double-blind part of the clinical trials was 1.7% and 1.3% in Rituxan and placebo treatment groups, respectively. 3 cardiovascular deaths occurred during the double-blind period of the RA studies including all rituximab regimens (3/769=0.4%) as 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 0.56 per 100 patient years (28 events in 26 patients), which is consistent with MI rates in the general RA population.

Immunogenicity: A total of 273/2578 (11%) patients with RA tested positive for HACA at any time after receiving Rituxan. HACA positivity was not associated with increased infusion reactions or other adverse reactions. Upon further treatment, the proportions of patients with infusion reactions were similar between HACA-positive and HACA-negative patients, and most reactions were mild to moderate. Four HACA-positive patients had serious infusion reactions, and the temporal relationship between HACA positivity and infusion reaction was variable. The clinical relevance of HACA formation in Rituxan treated patients is unclear.

Reference

1.

Rituxan [package insert]. South San Francisco, CA: Biogen Idec Inc. and Genentech USA, Inc.; February 2010.