Fatal Infusion Reactions in Rheumatoid Arthritis Patients Treated with Rituximab
June 29, 2011
On June 2, 2011, Health Canada, the agency responsible for monitoring drug use and safety in Canada sent a letter to Canadian health care providers regarding updated risks associated with the use of rituximab (Rituxan®) in rheumatoid arthritis (http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2011/rituxan_6_hpc-cps-eng.php). While there are currently no plans for a similar notification in the U.S., U.S. rheumatologists may wish to have more information about the circumstances that led to this letter.
The letter from Health Canada warns that, since rituximab was first approved in February 2006, there have been four reported cases of fatal infusion-related reactions in RA patients treated with this agent; none occurred in Canada. Brief details of the events are:
- A patient with a history of pericardial effusion and sleep apnea who developed shortness of breath and then cardiorespiratory arrest following the fifth course of rituximab. CPR was unsuccessful.
- A patient with a history of aortic insufficiency who experienced an anaphylactic reaction during the second infusion of a first course of rituximab. The patient died during a subsequent ICU hospitalization.
- Two additional patients died on the same day they received an infusion of rituximab. While no symptoms of an anaphylactic reaction were reported, and additional details are unavailable, the temporal relationship with the infusion raised the possibility of an infusion reaction.
Health Canada intends to work with the manufacturer to update the product monograph, but has no plans to restrict the availability of rituximab in Canada. The letter does stress the importance of premedication prior to rituximab infusions.
In general, infusion related events appear to be much less common and less serious when rituximab is used in the treatment of autoimmune diseases such as RA, as compared to the experience in non-Hodgkin’s lymphoma. In some countries, the product label for rituximab in rheumatic diseases stated this, and specifically noted the absence of deaths related to infusions. In those countries, the label will be changed. In the U.S., the FDA did not make such a distinction between treatment indications so the label already includes a black box warning for infusion reactions including potentially fatal ones.
The Bottom Line:
- Fatal infusion reactions have been reported with rituximab use, in both lymphoma and rheumatoid arthritis patients.
- Rheumatologists should remain aware of the potential for infusion reaction, particularly in patients with cardiopulmonary comorbidities, where the consequences may be more significant. Similar vigilance should presumably apply when rituximab is used in the treatment of vasculitis.
- Pre-medication with acetaminophen, an antihistamine (typically diphenhydramine), and intravenous corticosteroid is recommended for all rituximab infusions.
- No changes in the availability or labeling of rituximab are anticipated in the U.S.
Hotline Editors: Arthur Kavanaugh, MD, and Eric Ruderman, MD
Disclosures: Dr. Ruderman: Consultant for Roche/Genentech. Dr. Kavanaugh: Research studies for Roche/Genentech.
In addition to review by the editors, this Hotline has been reviewed by all members of the ACR Executive Committee, Communications and Marketing Committee and Drug Safety Committee.
The ACR Hotline is provided by the ACR Communications and Marketing Committee as a service to members. This Hotline reflects the views of the author(s) and does not represent a position statement of the American College of Rheumatology.
