Background/Purpose

Rituximab is a chimeric human/murine monoclonal antibody directed against the B cell specific antigen CD20. There is growing evidence that suggests Rituximab may also influence T cell immunity and thus predispose patients to opportunistic infections by this mechanism as well. Rituximab use, both as monotherapy and in combination with other immunosuppressants, is increasing in the pediatric population. Data regarding infection associated with Rituximab is limited and inconsistent. The most concerning side effect is the development of progressive multifocal leukoencephalopathy (PML), a fatal condition which has been reported rarely with Rituximab use. This study seeks to report adverse events associated with Rituximab use in the pediatric rheumatologic population.

Methods

A retrospective chart review of 20 pediatric patients with rheumatologic disease followed at Children’s Hospital Los Angeles between January 2007 and April 2014 was conducted. All patients received Rituximab and incidence of infection was assessed for a follow-up period of 6 months to 7 years following first Rituximab course.

Results

The majority of patients were female (55%) and Hispanic (70%), with 3 African American, 2 Caucasian and 1 Asian patient. The most common diagnoses were lupus (35%), dermatomyositis (30%), or overlap syndrome (20%). Sixty percent of patients received only one course of Rituximab and most (65%) received high dose glucocorticoids concurrently with their first course of Rituximab. Other immunosuppressants included methotrexate (55%), cyclophosphamide (CYC) (15%, with an average cumulative dose of 6g/m2), and anti-TNF therapy (15%). One patient each was on concurrent therapy with cyclosporine or azathioprine. There were 15 total infections in 9 patients during a mean follow up of 16.2 months (range 6 to 45 months) occurring on average 4.5 months (range 1 to 19 months) following Rituximab. Two infections (bacterial pneumonia and cellulitis) requiring hospitalization occurred in one patient who had received CYC as well. The remainder of infections were minor, 11 required outpatient antibiotics and 2 self-resolved. The majority of infections (87%) occurred in patients with lupus or an overlap syndrome. Only 1 patient developed prolonged hypogammaglobulinemia requiring supplemental IVIG. There were no cases of infusion related adverse events or PML in this cohort.

Conclusion

Overall the occurrence of significant adverse events following Rituximab was low in this pediatric cohort. Serious infections may be increased in those receiving combination therapy with CYC. Larger studies are needed to determine the attributable risk for infection from Rituximab alone versus that associated with underlying diagnosis or combination therapy. However, our results suggest that Rituximab use is safe and well-tolerated in a variety of pediatric rheumatologic conditions.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-of-rituximab-in-treating-pediatric-rheumatologic-disease/