Summary Safety Review - Xeljanz/Xeljanz XR (tofacitinib) - Assessing the Potential Risks of Serious Heart-related Problems and Cancer

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2022-01-12

Product

Xeljanz/Xeljanz XR (tofacitinib)

Potential Safety Issue

Serious heart-related problems (heart attack, stroke or cardiovascular death) and cancer (malignancies)

Key Messages

  • Xeljanz/Xeljanz XR (tofacitinib) is authorized for sale in Canada for the treatment of inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis, when other medicines do not work.
  • Health Canada reviewed the risks of serious heart-related problems (heart attack, stroke or cardiovascular death) and cancer (malignancies) with the use of Xeljanz/Xeljanz XR after a clinical research study showed an increase in these risks.
  • At the time of the review, the Canadian Product Monograph (CPM) for Xeljanz/Xeljanz XR included warnings and precautions for cancer and information on heart attacks. The purpose of this review was to assess whether additional warnings or other actions were required in Canada.
  • Health Canada's review of information from the clinical research study found a link between the use of Xeljanz/Xeljanz XR and the risks of serious heart-related problems and cancer. These risks were increased especially in older patients, in patients who are current or past smokers, and in patients with cardiovascular or cancer risk factors.
  • Health Canada has worked with the manufacturer to update the CPM to highlight the risks of serious heart-related problems and cancer, including a warning statement about the use of Xeljanz/Xeljanz XR in specific populations.
  • Health Canada will also communicate important safety information with the use of Xeljanz/Xeljanz XR to healthcare professionals and the public through a Health Product Risk Communication and a Public Advisory.
  • Based on findings from the clinical research study with Xeljanz/Xeljanz XR, Health Canada is reviewing the risks of serious heart-related problems, cancer, and blood clots (thrombosis) with 2 other drugs in the same drug class as Xeljanz/Xeljanz XR. Health Canada will inform the public of any new safety findings, as needed, once the review is completed.

Overview

Health Canada reviewed the risks of serious heart-related problems and cancer with the use of Xeljanz/Xeljanz XR.

Health Canada started this safety review after the manufacturer advised of a clinical research study showing an increased risk of serious heart-related problems and cancer (lymphoma and lung cancer). This clinical research study looked at the long-term safety of Xeljanz/Xeljanz XR in patients suffering from rheumatoid arthritis, an immune system disease that causes damage and inflammation of joints, who were 50 years of age or older with at least 1 additional cardiovascular risk factor.1

Use in Canada

  • Xeljanz and Xeljanz XR are prescription drugs authorized for sale in Canada to treat rheumatoid arthritis when other medicines do not work. Xeljanz is also authorized to treat psoriatic arthritis, an inflammation of the joints with red scaly patches on the skin, or ulcerative colitis, a large intestine inflammation causing sores and bleeding, when other medicines do not work.
  • Xeljanz has been marketed in Canada since 2014 and is currently available as 5 mg and 10 mg tablets. Xeljanz XR has been marketed in Canada since 2018 and is currently available as 11 mg extended-release tablets.
  • The number of prescriptions filled has been increasing from about 11,000 to 65,000 in Canadian retail pharmacies between 2016 and 2020.

Safety Review Findings

  • Health Canada reviewed the clinical research study findings.
  • This study compared Xeljanz/Xeljanz XR with another type of drug used to treat arthritis called tumor necrosis factor inhibitors in patients with rheumatoid arthritis, who were 50 years of age or older with at least 1 additional cardiovascular risk factor.
  • The study found an increased risk of serious heart-related problems and cancer in patients treated with Xeljanz/Xeljanz XR. This information established a link between the use of Xeljanz/Xeljanz XR and these risks. Serious heart-related problems and cancer were increased especially in older patients, in patients who are current or past smokers, and in patients with cardiovascular or cancer risk factors.

Conclusions and actions

  • Health Canada's review of the clinical research study found a link between the use of Xeljanz/Xeljanz XR and the risks of serious heart-related problems and cancer.
  • Health Canada has worked with the manufacturer to update the CPM to highlight the risks of serious heart-related problems and cancer, including a warning statement about the use of Xeljanz/Xeljanz XR in older patients, patients who are current or past smokers, and patients with cardiovascular or cancer risk factors.
  • Health Canada will also communicate important safety information with the use of Xeljanz/Xeljanz XR to healthcare professionals and the public through a Health Product Risk Communication and a Public Advisory.
  • Based on findings from the clinical research study with Xeljanz/Xeljanz XR, Health Canada is reviewing the risks of serious heart-related problems, cancer, and thrombosis with 2 other drugs in the same drug class as Xeljanz/Xeljanz XR. Health Canada will inform the public of any new safety findings, as needed, once the review is completed.
  • Health Canada will continue to monitor safety information involving Xeljanz/Xeljanz XR, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

Additional information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of Xeljanz/Xeljanz XR both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.