Janus kinase inhibitors (JAKi)

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status
Opinion provided by Committee for Medicinal Products for Human Use

Overview

EMA confirms measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders

On 23 January 2023, EMA’s human medicines committee (CHMP) endorsed the measures recommended by the Pharmacovigilance Risk Assessment Committee (PRAC) to minimise the risk of serious side effects with Janus kinase (JAK) inhibitors used to treat several chronic inflammatory disorders. These side effects include cardiovascular conditions, blood clots, cancer and serious infections..

These medicines should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past and those at increased risk of cancer.

JAK inhibitors should be used with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism, VTE) other than those listed above. Further, the doses should be reduced in patient groups who are at risk of VTE, cancer or major cardiovascular problems, where possible.

The recommendations follow a review of available data, including the final results from a clinical trial1 of the JAK inhibitor Xeljanz (tofacitinib) and preliminary findings from an observational study involving Olumiant. The review also included advice from an expert group of rheumatologists, dermatologists, gastroenterologists and patient representatives.

The review confirmed Xeljanz increases the risk of major cardiovascular problems, cancer, VTE, serious infections and death due to any cause when compared with medicines belonging to the class of TNF-alpha inhibitors. EMA has now concluded that these safety findings apply to all approved uses of JAK inhibitors in chronic inflammatory disorders (rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, ulcerative colitis, atopic dermatitis and alopecia areata).

The product information for JAK inhibitors used to treat chronic inflammatory disorders will be updated with the new recommendations and warnings. In addition, the educational material for patients and healthcare professionals will be revised accordingly.


1 Ytterberg SR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. New Engl J Med 2022;386(4):316-326. doi: 10.1056/NEJMoa2109927.

Key facts

About this medicine
Approved name
Janus kinase inhibitors (JAKi)
International non-proprietary name (INN) or common name
  • tofacitinib
  • abrocitinib
  • baricitinib
  • upadacitinib
  • filgotinib
Associated names
  • Xeljanz
  • Cibinqo
  • Olumiant
  • Rinvoq
  • Jyseleca
About this procedure
Current status
Opinion provided by Committee for Medicinal Products for Human Use
Reference number
EMEA/H-A20/1517/C/004214/0048; EMEA/H-A20/1517/C/005452/0003; EMEA/H-A20/1517/C/004085/0032; EMEA/H-A20/1517/C/004760/0017; EMEA/H-A20/1517/C/005113/0014
Type
Article 20 procedures

This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of quality, safety or efficacy issues.

Authorisation model
Centrally authorised product(s)
Decision making model
PRAC-CHMP-EC
Key dates and outcomes
Procedure start date
10/02/2022
PRAC recommendation date
27/10/2022
CHMP opinion/CMDh position date
12/01/2023
Outcome
Risk minimisation measures

All documents

Procedure started

Under evaluation

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Opinion provided by Committee for Medicinal Products for Human Use

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

  • Overview - lay-language summary of the stage of the procedure
  • Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
  • Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
  • List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
  • Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
  • List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
  • List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
  • Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
  • Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
  • Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
  • Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
  • Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
  • Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
  • Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
  • Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.

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