The MHRA has announced new measures to reduce the risks of major cardiovascular events, malignancy, venous thromboembolism, serious infections, and increased mortality linked to JAK inhibitors.
Janus kinase (JAK) inhibitors are used to treat chronic inflammatory disorders such as severe arthritis, psoriatic arthritis, inflammatory bowel diseases, and atopic eczema. However, the Medicines and Healthcare products Regulatory Authority (MHRA) has warned that these drugs can increase a patient’s risk of developing major cardiovascular problems, cancer, venous thromboembolism (VTE), serious infections, and death, when compared with TNF-alpha inhibitors.
A spokesperson for the MHRA pointed out that the new risk minimisation measures for JAK inhibitors were consistent with those introduced for tofacitinib (Xeljanz) in 2020 and 2021. The new measures followed the observation of an increased incidence of malignancy, major adverse cardiovascular events (MACE), serious infections, VTE, and mortality, when compared to those patients treated with TNF-alpha inhibitors, in trials of patients with rheumatoid arthritis with certain risk factors when treated with some JAK inhibitors, particularly tofacitinib.
The new MHRA advice affected abrocitinib (Cibinqo▼), baricitinib (Olumiant), upadacitinib (Rinvoq▼), and filgotinib (Jyseleca▼) when used for chronic inflammatory disorders, the spokesperson explained.
Avoid Prescribing JAK Inhibitors for Certain Risk Groups
Following the findings for tofacitinib, in 2022 the European Medicines Agency conducted a review of all JAK inhibitors indicated for inflammatory diseases.
The identified risks were now considered "class effects" across JAK inhibitors used for chronic inflammatory disorders, the agency said.
The MHRA has advised healthcare professionals to avoid prescribing these drugs unless there were no suitable alternatives in patients with the following risk factors:
- Age 65 years or older
- Current or past long-time smoking
- Other risk factors for cardiovascular disease or malignancy
The MHRA also advised using caution if prescribing in patients with risk factors for VTE other than those listed, and, where applicable, to use lower doses in patients with risk factors.
"The incidence of non-melanoma skin cancer in the study was also higher with tofacitinib than with a TNF inhibitor," cautioned the MHRA spokesperson. Healthcare professionals were advised to perform periodic skin examinations in all patients on JAK inhibitor drugs, with patients advised to examine their skin periodically too.
As a consequence, changes were being made to the product information for all JAK inhibitor medicines authorised for inflammatory diseases to note the updated risk characterisation and expanded risk minimisation measures, alerted the MHRA.
The MHRA spokesperson emphasised that the new advice was not relevant for use of JAK inhibitors (ruxolitinib (Jakavi▼) and fedratinib (Inrebic▼) to treat myeloproliferative disorders, nor baricitinib used outside the licence in the short-term treatment of COVID-19.
Safety of Isotretinoin Treatment to be Strengthened
In a second announcement, the MHRA said that the Isotretinoin Expert Working Group of the Commission on Human Medicines had made recommendations to strengthen the safety of isotretinoin treatment.
These included new warnings, the need for consistent monitoring requirements for psychiatric side effects, the introduction of new monitoring requirements for sexual side effects, and additional oversight of the initiation of treatment for patients younger than 18 years.
"No new action from healthcare professionals is needed for now," the MHRA said, and added that further communications would be issued once the recommendations were being implemented.
