Archived – Use of Kineret®(anakinra) in Combination with Etanercept

IMPORTANT DRUG SAFETY INFORMATION
Use of Kineret^® (anakinra) in Combination with etanercept

December 17, 2002

Dear Healthcare Professional:

Amgen Canada Inc., in consultation with Health Canada, would like to bring to your attention results of a recently completed clinical trial conducted in patients receiving concurrent Kineret^® and etanercept therapy. Kineret^® is a recombinant, nonglycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra) indicated to reduce the signs and symptoms of active rheumatoid arthritis.

A recently completed trial demonstrated that:

• patients receiving concurrent Kineret® and etanercept resulted in a higher incidence of serious infections than in patients receiving etanercept alone.
• no therapeutic benefit of the combination treatment over etanercept alone was observed in this study

This clinical trial was a 24-week randomized, controlled trial in 242 patients in the United States with rheumatoid arthritis who had not previously been treated with biologic agents. The objective of this study was to compare the efficacy and safety of etanercept alone with etanercept plus Kineret^®. The results of the study confirmed a serious infection incidence of 7% in the combination group, which was previously reported in a small open-label trial where Kineret^® was added to patients already being treated with etanercept. This incidence was higher than in the etanercept alone group (0%). All cases of serious infection reported in this trial were either bacterial or viral in origin. The incidence reported in previous trials with Kineret^® as a monotherapy was 1.8%.

Amgen Canada Inc. is taking this opportunity to remind physicians of the current wording in the "Warnings" section of the Canadian Kineret^® (anakinra) Prescribing Information which refers to combination therapy:

"...use of Kineret™ with TNF blocking agents should only be done with extreme caution and when no satisfactory alternatives exist."

Amgen Canada Inc., in accordance with Health Canada, will amend the Canadian Prescribing Information to include the lack of therapeutic effect with combination therapy.

The identification, characterization, and management of drug-related adverse events are dependent on the active participation of healthcare professionals in adverse drug reaction reporting programs. Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use. Should you have any questions or require additional information regarding the use of Kineret^®, please contact Amgen Canada's Medical Information at 1-800-665-4273 extension 360.

Any occurrences of serious infection or other serious and/or unexpected adverse events in patients receiving Kineret^®(anakinra) should be reported to Amgen or the Marketed Health Products Directorate of Health Canada at the following addresses:

AMGEN Canada Inc.
6755 Mississauga Road, Suite 400
Mississauga, Ontario
L5N 7Y2

or call toll free at 1-800-665-4273

The new clinical data being conveyed in this letter reflects data obtained during a clinical trial and not data from spontaneously reported adverse events. Reporting rates determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to underestimate the risks associated with Kineret^® (anakinra).

Sincerely,
AMGEN Canada Inc.

original signed by

Viken Paragamian
Director Scientific Affairs

Any suspected adverse drug reactions can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Marketed Health Products Directorate
Health Canada
Address Locator: 0201C2
Ottawa, Ontario, K1A 1B9
Tel: (613) 957-0337 or Fax: (613) 957-0335
Toll free for consumers and health professionals:
Tel: 866 234-2345, Fax: 866 678-6789
cadrmp@hc-sc.gc.ca

The ADR Reporting Form and the ADR Guidelines can be found on the TPD web site or in The Canadian Compendium of Pharmaceuticals and Specialties.