PRAC November 2019: recommendations for the medicinal products Lemtrada and Xeljanz

During the meeting of 28 - 31 October 2019, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) implemented measures to minimise risk of serious side effects with Lemtrada. Furthermore, the PRAC recommended Xeljanz to be used with caution for all patients at high risk of blood clots.

Lemtrada for multiple sclerosis: measures to minimise risk of serious side effects
The PRAC recommends restrictions on the use of Lemtrada (alemtuzumab) in patients with relapsing remitting multiple sclerosis. The recommendations reflect PRAC’s review of reports concerning rare but serious effects, including deaths, from immune-mediated conditions (caused by the body’s defence system not working properly) and serious heart, circulation and bleeding disorders, including stroke. Immune-mediated conditions can occur many months after treatment while serious disorders of the heart, circulation and bleeding may develop within days of receiving Lemtrada.

The PRAC recommends restricting Lemtrada for use in adults with relapsing remitting multiple sclerosis that is highly active despite adequate treatment with at least one disease-modifying therapy or if the disease is worsening rapidly with at least two disabling relapses in a year and brain-imaging showing new damage. Also, Lemtrada must no longer be used in patients with certain heart, circulation or bleeding disorders or in patients who have auto-immune disorders other than multiple sclerosis.

New measures have been recommended for identifying and promptly dealing with adverse effects that might occur after treatment with Lemtrada. It should be given in a hospital with ready access to intensive care facilities and specialists who can manage serious adverse reactions.

The PRAC also recommends updating the physician’s guide and the patient information pack with advice to minimise the risk of serious heart, circulation and bleeding disorders that may occur shortly after the infusion (drip) as well as autoimmune conditions that could occur many months after the last Lemtrada treatment.

The new recommendations replace the temporary measures issued in April 2019 while the PRAC’s review was under way.

The PRAC recommendations will now be sent to EMA’s human medicines committee (CHMP), which will adopt the Agency’s final opinion.

The medicinal product Lemtrada is marketed in Belgium.

More information is available on the EMA website

 

Xeljanz to be used with caution for all patients at high risk of blood clots
A PRAC review has concluded that Xeljanz (tofacitinib) could increase the risk of blood clots in the lungs and in deep veins in patients who are already at high risk.

As a result, the PRAC recommends that Xeljanz should be used with caution in patients at high risk of blood clots. In addition, the maintenance doses of 10 mg twice daily should not be used in patients with ulcerative colitis who are at high risk unless there is no suitable alternative treatment. Further, the PRAC recommends that patients older than 65 years of age should be treated with Xeljanz only when there is no alternative treatment.

Patients at high risk of blood clots include those who have had a heart attack or have heart failure, cancer, inherited blood clotting disorders or a history of blood clots, as well as patients who take combined hormonal contraceptives, are receiving hormone replacement therapy, are undergoing major surgery or are immobile. Doctors should also consider other factors that may increase the risk of blood clots including age, obesity, diabetes, hypertension or smoking.

These recommendations follow the PRAC’s review of an ongoing study (study A3921133) in patients with rheumatoid arthritis and an increased risk of cardiovascular disease. This study showed an increased risk of blood clots in deep veins and in the lungs with both the 5 mg and 10 mg twice daily doses of Xeljanz as compared with patients taking TNF-inhibitors. The PRAC also re-assessed additional data from earlier studies. All data combined showed that the risk of blood clots was higher in patients taking Xeljanz, especially with the 10 mg twice daily dose and in those being treated for an extended period. Results also showed a further increased risk of serious and fatal infections in patients older than 65 years of age.

The Summary of Product Characteristics and the Patient Leaflet for Xeljanz will now be updated with new warnings and recommendations based on data from the study and will list blood clots as an uncommon side effect occurring in between 1 in 1,000 and 1 in 100 patients.

The PRAC also recommends updating the physician’s guide and the patient alert card with advice to minimise the risk of blood clots. Patients who have questions about their treatment or their risk of blood clots should contact their doctor.

The new recommendations replace the measures put in place at the start of the review in May 2019 when the PRAC recommended that doctors stop prescribing the 10 mg twice daily dose of Xeljanz for patients at high risk of blood clots in the lungs while it reviewed data from study A3921133.The PRAC’s recommendations will now be sent to the EMA’s human medicines committee (CHMP), which will adopt the Agency’s final opinion.

The medicinal product Xeljanz is marketed in Belgium.

More information is available on the EMA website.

Last updated on
17/12/2019