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| The United Kingdom: Tofacitinib (Xeljanz▼): new measures to minimise risk of major adverse cardiovascular events and malignancies (English only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces that tofacitinib should not be used in patients older than 65 years of age, people who are current or past smokers, or individuals with other cardiovascular (such as diabetes or coronary artery disease) or malignancy risk factors unless there are no suitable treatment alternatives.
Information on cardiovascular events
A clinical safety trial in patients with rheumatoid arthritis aged 50 years or older with at least one cardiovascular risk factor (Study A3921133) found that a Janus kinase (JAK) inhibitor tofacitinib was associated with an increased risk of major adverse cardiovascular events compared with TNF-alpha inhibitors (etanercept or adalimumab). The predictive risk factors identified were: age older than 65 years, current or past smoking, history of diabetes, and history of coronary artery disease (including past myocardial infarction, coronary heart disease, stable angina pectoris, or coronary artery procedures). Healthcare professionals are advised to only consider use of tofacitinib in patients with these cardiovascular risk factors, irrespective of indication, if no suitable treatment alternative is available.
Information on malignancy
The same clinical safety trial in patients with at least one cardiovascular risk factor (some of which are also malignancy risk factors) found that tofacitinib was associated with an increased risk of malignancies (with the analysis excluding non-melanoma skin cancer [NMSC]), particularly lung cancer and lymphoma, compared with TNF-alpha inhibitors. The predictive risk factors identified were: age older than 65 years and current or past smoking. Healthcare professionals are advised to only consider use of tofacitinib in patients with these and other malignancy risk factors (current or previous history of malignancy other than successfully treated NMSC), irrespective of indication, if no suitable alternative treatment is available.
Advice for healthcare professionals to give to patients:
• tofacitinib treatment has been associated with an increased risk of heart attacks and certain cancers compared with another type of treatment (TNF-alpha inhibitors) – the incidence of these events is low and they have been linked to existing risk factors for these conditions such as older age or smoking
• patients who are already at increased risk of cardiovascular events or cancers should only be offered treatment with tofacitinib if their doctor feels there are no other suitable treatment options for their condition
• do not stop taking tofacitinib without first talking to the doctor
• read accompanied product information and communicate with the healthcare professionals for the concern about any side effects
In the United Kingdom (UK), tofacitinib (Xeljanz▼) is a Janus kinase (JAK) inhibitor authorised for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. Study ORAL Surveillance (A3921133) was a large, randomised, active-controlled, clinical safety trial to evaluate the safety of tofacitinib versus tumour necrosis factor (TNF)-alpha inhibitors. The study involved 4,362 patients with rheumatoid arthritis aged 50 years or older and with at least one additional cardiovascular risk factor. In 2018, secondary findings of this study led to new measures to minimise risks of venous thromboembolism and serious and fatal infections with tofacitinib.
The co-primary endpoints of study A3921133 were adjudicated major adverse cardiac events and adjudicated malignancies (with the analysis excluding non-melanoma skin cancer).
Doses of tofacitinib included in the study were 5mg twice-daily and 10mg twice-daily and endpoints in these groups were compared with those from patients randomised to TNF-alpha inhibitors (etanercept, 50mg once a week subcutaneously, or adalimumab, 40mg once every other week subcutaneously).
In 2021, final results from study A3921133 showed tofacitinib to be associated with an increased incidence of non-fatal myocardial infarction and malignancies, particularly lung cancer and lymphoma.
These results prompted a review into these risks of tofacitinib and how they should be minimised. Prescribers of tofacitinib were informed of the final trial results in a letter in March 2021 with a further letter with the final recommendations sent in July 2021. In the UK, the product information and educational materials for healthcare professional and patients will also be updated with this information.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/tofacitinib-xeljanzv-new-measures-to-minimise-risk-of-major-adverse-cardiovascular-events-and-malignancies
In Hong Kong, there are 3 registered pharmaceutical products containing tofacitinib, namely Xeljanz Tablets 5mg (HK-63303), Xeljanz XR Extended Release Tablets 11mg (HK-66141) and Xeljanz Tablets 10mg (HK-66833) which are registered by Pfizer Corporation Hong Kong Limited. All products are prescription-only medicines. So far, the Department of Health (DH) has received 8 cases of adverse drug reaction related to tofacitinib (of which one case is lung cancer and 3 cases are deep vein thrombosis).
Related news on the risk of serious heart-related problems and cancer of tofacitinib was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 5 Feb 2021, with the latest update posted on 2 Sep 2021. Letters to inform local healthcare professionals were issued by the DH on 15 Jun 2021. As previously reported, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/ Thursday, October 7, 2021
Issued at HKT 15:15
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