Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults
Authors: Casey Lee McAtee, Joseph Lubega, Kristen Underbrink, Kristen Curry, Pavlos Msaouel, Martha Barrow, Eyal Muscal, Timothy Lotze, Poyyapakkam Srivaths, Lisa R. Forbes, Carl Allen, M. Brooke Bernhardt
Journal: JAMA Network Open (2021)

IMPORTANCE Rituximab is among the most frequently used immunotherapies in pediatrics.Few studies have reported long-term adverse events associated with its use for children.OBJECTIVE To describe the use of rituximab and to assess whether its use is associated with shortor long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital.Patterns of adverse events, infections, and immune recovery are described.Data analyses were conducted from December 2019 to June 2020.EXPOSURE One or more doses of rituximab. MAIN OUTCOMES AND MEASURESAdverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels.Survival models and logistic regression analyses were used to identify associated risk factors of infectious and noninfectious adverse drug events. RESULTSWe identified 468 patients receiving at least 1 dose of rituximab.The total follow-up time was 11 713 person-months.Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8)years, and 209 (44.7%) were self-reported White Hispanic.Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%).Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent.Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections.Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection.Among 135 patients (28.8%) followed up to B cell count recovery, CD19 + or CD20 + cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts.Recovery of CD27 + memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months).Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM.(continued) Key Points Question Is the use of rituximab for young people associated with short-or long-term adverse events?Findings This cohort study identified 468 patients younger than 21 years receiving rituximab for more than 25 indications, among whom infectious and noninfectious adverse events were common.The majority of these events were mild, but a small population experienced prolonged immune suppression and severe infections following even single courses of rituximab.Meaning Findings suggest that rituximab appears to be well tolerated among young people, but the observed frequent infections and prolonged recovery of B lymphocyte numbers highlight the need for better strategies to mitigate infection risk in this population.