Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 28-31 October 2019

31 October 2019

PRAC recommends measures to minimise risk of serious side effects with Lemtrada for multiple sclerosis

EMA’s safety committee (PRAC) recommended 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.

The PRAC had issued interim measures on Lemtrada while reviewing reports of serious reactions. The PRAC completed the review and recommended that Lemtrada must no longer be used in in patients with certain heart, circulation or bleeding disorders or in patients who have auto-immune disorders other than 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 disorders of the heart, circulation and bleeding.

More information is available below.

PRAC recommends cautious use of Xeljanz for all patients at high risk of blood clots

The PRAC 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.

The PRAC recommended 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. Patients older than 65 years of age should be treated with Xeljanz only when there is no other appropriate treatment.

These recommendations follow the PRAC’s review of an ongoing study in patients with rheumatoid arthritis and an increased risk of cardiovascular disease. The 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 (medicines that help reduce inflammation).

More information is available below.

Agenda

Agenda - PRAC draft agenda of meeting 28-31 October 2019

Draft Reference Number: EMA/PRAC/585930/2019

PRAC recommendation - Lemtrada Article 20 procedure

Lemtrada

Lemtrada Article 20 procedure - Lemtrada for multiple sclerosis: measures to minimise risk of serious side effects

Reference Number: EMA/583516/2019

PRAC recommendation - Xeljanz Article-20 procedure

Xeljanz

Xeljanz Article-20 procedure - Xeljanz to be used with caution for all patients at high risk of blood clots

Reference Number: EMA/584781/2019

PRAC statistics: November 2019

PRAC statistics: November 2019

Glossary:

• Safety signal assessments. A safety signal is information on a new or known adverse event that is potentially caused by a medicine and that warrants further investigation. Signals are generated from several sources such as spontaneous reports, clinical studies and the scientific literature. More information can be found under Signal management.
• Periodic safety update reports, abbreviated as PSURs, are reports prepared by the marketing authorisation holder to describe the worldwide safety experience with a medicine in a defined period after its authorisation. PSURs for medicinal products that contain the same active substance or the same combination of active substances, but have different marketing authorisations and are authorised in different EU Member States, are jointly assessed in a single assessment procedure. More information can be found under Periodic safety update reports: questions and answers.
• Risk management plans, abbreviated as RMPs, are detailed descriptions of the activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicines. Companies are required to submit an RMP to EMA when applying for a marketing authorisation. RMPs are continually updated throughout the lifetime of the medicine as new information becomes available. More information is available under Risk-management plans.
• Post-authorisation safety studies, abbreviated as PASSs, are studies carried out after a medicine has been authorised to obtain further information on its safety, or to measure the effectiveness of risk-management measures. The PRAC assesses the protocols (aspects related to the organisation of a study) and the results of PASSs. More information can be found under Post-authorisation safety studies (PASS).
• Referrals are procedures used to resolve issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. In a referral related to safety of medicines, the PRAC is requested by a Member State or the European Commission to conduct a scientific assessment of a particular medicine or class of medicines on behalf of the EU. More information can be found under Referral procedures.

Ongoing referrals

Procedure	Status	Update
Article-31 procedure: Cyproterone-containing medicinal products	Under evaluation	PRAC adopted a list of outstanding issues (LoOI).
Article-31 procedure: Estradiol-containing (0.01% w/w) medicinal products for topical use	PRAC recommendation issued on 3 October 2019	Following the PRAC’s recommendation of 3 October 2019, one of the marketing authorisation holders involved with this review has requested a re-examination. Upon receipt of the grounds for the request, the PRAC will start a re-examination, which is expected to conclude at the PRAC meeting of 13-16 January 2020.
Article-20 procedure: Fluorouracil and fluorouracil related substances (capecitabine, tegafur and flucytosine) containing medicinal products	Under evaluation	PRAC continued its assessment.
Article-31 procedure: Leuprorelin-containing depot medicinal products	Under evaluation	PRAC adopted a list of outstanding issues (LoOI).
Article-20 procedure: Picato	Under evaluation	PRAC continued its assessment