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Study eyes serious adverse events from long-term rituximab use in MS



– An analysis of two large cohorts treated with rituximab (Rituxan) showed that the rate of serious infections was 8.1%, yet no life-threatening infusion reactions occurred.

The finding comes from a retrospective chart review of 500 patients treated at the Rocky Mountain Multiple Sclerosis Center at the University of Colorado at Denver, Aurora, and 269 treated at the New York University Multiple Sclerosis Comprehensive Care Center.

Brandi L. Vollmer of the University of Colorado at Denver Doug Brunk/MDedge News

Brandi L. Vollmer

At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, one of the study authors, Brandi L. Vollmer, MPH, noted that while rituximab is used off-label to treat multiple sclerosis (MS) and related disorders, limited long-term data for MS patients exist. Ms. Vollmer, a professional research assistant in the department of neurology in the division of neuroimmunology at the University of Colorado at Denver, and her associates identified all patients at the two MS centers who received at least one dose of rituximab. They reviewed patient charts from rituximab start date until 12 months after the last rituximab end date, or last ocrelizumab (Ocrevus) infusion in cases where patients switched to ocrelizumab without interruption with any other disease-modifying therapy. Data were abstracted from each chart using a case report form that systematically queried for demographic and clinical characteristics, serious adverse events, and significant laboratory abnormalities. The researchers used descriptive statistics to describe the sample group.

Key outcomes of interest were infusion reactions that were life-threatening or resulted in a hospitalization; infections that resulted in hospitalization, the need for IV antibiotics, or extended antibiotics; abnormal lab values; new diagnosis of malignant cancer; new diagnosis of autoimmune disease; diagnosis of serious thromboembolism; and mortality within 12 months of last infusion. At baseline, the mean age of the 769 patients was 43 years, 69% were female, 64% were white, and 16% were black. More than half (58%) had a diagnosis of relapsing-remitting MS, followed by secondary progressive MS (20%), primary progressive MS (11%), neuromyelitis optica spectrum disorder (9%), or other, and their mean disease duration was 8 years.

The researchers reported that the mean cumulative rituximab dose was 4,124 mg (median of 3,000 mg), the mean dose of ocrelizumab for ocrelizumab-switchers was 1,087 mg, and the mean time of follow-up was 33 months. Infections while on rituximab/ocrelizumab resulting in a hospitalization were observed in 50 patients (6.5%), which were primarily urinary tract infections (UTIs; 19 cases), pneumonia (12 cases), and sepsis (12 cases), while 7 patients (0.9%) experienced an infection that resulted in extended dosing antibiotics, including 5 recurrent UTIs, 1 case of bacteremia, and 1 case of osteomyelitis.

Ms. Vollmer and her colleagues also found that five patients (0.7%) experienced an infection that resulted in IV antibiotics without hospitalization, including one case each of pneumonia, cellulitis, UTI, infected wound, and aspiration pneumonia with respiratory syncytial virus. Serious de novo diagnoses while on rituximab were reported for 18 patients (2%), including autoimmune disease in 4, non-skin neoplasm in 7, and serious thromboembolic events in 7.

No patient experienced an infusion reaction requiring hospitalization. However, one patient received epinephrine after seeking care at an emergency department post infusion. Twelve patients (2%) died within 12 months of their last rituximab dose, although none were deemed by the treating clinician to be related to rituximab. Significant neutropenia was observed in 12 (2%), lymphopenia in 46 (6%), and IgG values below 500 mg/dL in 28 (4%).

“So far, this is just a descriptive analysis,” Ms. Vollmer said. “We want to look further into how abnormal lab values correlate with serious infections in particular.”

She acknowledged certain limitations of the study, including its retrospective design. Ms. Vollmer reported having no financial disclosures. Many of her coauthors reporting having numerous financial ties to the pharmaceutical industry.

SOURCE: Vollmer B et al. ACTRIMS Forum 2019, Poster 113

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