Arcoxia - referral

Current status

European Commission final decision

Overview

Etoricoxib is a selective inhibitor of COX-2 (cyclooxygenase 2) indicated in the symptomatic relief of osteoarthritis (OA, 30-60mg once daily (od)), rheumatoid arthritis (RA, 90mg od) and the pain and signs of inflammation associated with acute gouty arthritis (120mg od)

This referral procedure relates to a request for arbitration concerning a type II variation for a new indication to include treatment of ankylosing spondylitis (AS), at a recommended daily dose of 90mg. At the end of the mutual recognition procedure, there was a discrepancy between different European Union (EU) Member States regarding the safety of etoricoxib at the 90mg dose in the new proposed indication. As these concerns were not resolved during the course of the procedure, a notification of an official referral for arbitration under Article 6(12) of Commission Regulation EC No 1084/2003 to the CHMP was made by France on 19 September 2007.

The main unresolved areas of concern identified by France were concerns regarding long term safety of a daily dose of 90mg etoricoxib in the view of possible increased cardiovascular (CV) risk related to the use of the 90mg dose in the ankylosing spondylitis (AS) indication. France considered that a review of the benefit/risk profile of Arcoxia was needed.

The arbitration procedure was discussed by the CHMP at its plenary meeting in September 2007 and a Rapporteur (Dr. Karl Broich) and Co-Rapporteur (Dr. Matthew Thatcher) were appointed. The referral procedure was initiated on 20 September 2007 with the adoption of a CHMP list of questions that were to be addressed by the marketing authorisation holders (MAHs). During the February 2008 plenary meeting Dr. Rafe Survana was appointed Co-Rapporteur, replacing Dr. Matthew Thatcher.

Written explanations were provided by the MAHs on 14 December 2008, 5 May 2008, 12 June 2008 and 20 June 2008.

The CHMP concluded that the data confirmed the known renovascular safety profile of etoricoxib (hypertension, oedema and congestive heart failure). The data further confirmed a similar CV thrombotic risk like diclofenac and some degree of upper gastrointestinal (GI) safety advantage over naproxen and diclofenac (though no particular lower GI safety advantage). There was little direct comparative safety data for individual non-steroidal anti-inflammatory drugs (NSAIDs) other than diclofenac and naproxen. It was therefore difficult to determine risks for etoricoxib compared with ibuprofen, ketoprofen or other less-commonly used NSAIDs.

Drug utilisation data showed that some patients with high blood pressure are being initiated on etoricoxib. The CHMP therefore recommended the strengthening of the contraindication in hypertensive patients and alerts prescribers that blood pressure needs to be monitored, especially within 2 weeks of treatment initiation. Healthcare professionals were to be reminded of these measures through a communication letter (Dear Healthcare Professional Letter).

Data from clinical studies showed clinically meaningful treatment effect for the 90mg etoricoxib once daily dose for AS indication; however, some data are available to indicate that lower doses might also show effect. The CHMP therefore recommended that dose finding studies should be explored to conclude if treatment with 60mg once daily would also be adequate for some patients.

Based on the review of the available data, the CHMP considered that the benefits of etoricoxib outweigh the risks in the treatment of ankylosing spondylitis.

On 26 June 2008, the CHMP, having considered the data provided by the MAHs, recommended the granting of the variation to the marketing authorisations.

The list of product names concerned is given in Annex I. The scientific conclusions are provided in Annex II, the amended product information in Annex III and the conditions of the marketing authorisation in Annex IV.

The final opinion was converted into a decision by the European Commission on 9 September 2008.

Opinion following an Article 6(12) referral for Arcoxia International Non-Proprietary Name (INN): etoricoxib: Background information

AdoptedReference Number: EMEA/438258/2008

Key facts

About this medicine

• Approved name:
  Arcoxia
• International non-proprietary name (INN) or common name:
  etoricoxib

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CHMP/438258/08
• Type:
  Article 6(12) referrals (prior to January 2010)

  This type of referral was triggered for a medicine that had been authorised by mutual recognition or via the decentralised procedure when there was disagreement between Member States on a variation (type II). This referral has been replaced by Article 13 referrals.

Key dates and outcomes

• CHMP opinion date:
  26/06/2008
• EC decision date:
  09/09/2008

All documents

Arcoxia - Article 6 (12) referral - Annex I, II, III, IV

Adopted

Opinion following an Article 6(12) referral for Arcoxia International Non-Proprietary Name (INN): etoricoxib: Background information

AdoptedReference Number: EMEA/438258/2008

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.