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COX-2 Inhibitors

Removed from the Positive List (2004)

http://www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=4162

The selective COX-2 inhibitors (ATC group M-01-AH) are no longer granted general (automatic) reimbursement. Patients – in consultation with their doctor – are therefore encouraged to consider using another medicinal product eligible for reimbursement.

Criteria for general reimbursement are not met

On 28 September 2004, the Danish Medicines Agency decided that the selective COX-2 inhibitors in the ATC group M-01-AH should no longer be granted general (automatic) reimbursement with effect from 25 October 2004. The ATC group M-01-AH includes the medicinal products Celebra®, Arcoxia® and Vioxx® (until 1 October 2004). The decision is based on an evaluation from the Danish Medicines Agency concluding that the criteria for granting general (automatic) reimbursement for these medicinal products are not fulfilled.

Subsequently, Merck Sharp & Dohme has withdrawn Vioxx® from the market as of 1 October 2004. This decision was based on an unexpectedly high prevalence of cardiovascular adverse reactions in a clinical study with Vioxx®, cf. announcement of 30 September 2004 on withdrawal of Vioxx® on the Danish Medicines Agency’s website.

Changed relationship between benefits and risks of COX-2 inhibitors

The Danish Medicines Agency’s decision to remove selective COX-2 inhibitors from the positive list was primarily based on the CPMP’s (now CHMP) evaluation.

It appears from the evaluation that the balance between benefits and risks of the selective COX-2 inhibitors has changed, cf. announcement of 18 June 2004 on COX-2 inhibitors on the Danish Medicines Agency’s website (link in fact box to the right).

Consequently, the European Commission decided that special warnings and rules of caution about the use of selective COX-2 inhibitors must be included in the respective summaries of product characteristics.

Doctors should especially be careful when treating patients with serious risks of developing gastrointestinal complications in connection with NSAIDs (Non-Steroidal Anti-Inflammatory Drugs, medicinal products reducing fever and relieving pain).

These are the patients concerned:

  • elderly patients who use other NSAIDs or acetylsalicylic acid at the same time
  • patients who have previously had gastrointestinal disease such as ulcer and gastrointestinal bleeding.

The changes to the summaries of product characteristics have already been implemented.

According to the Danish Medicines Agency’s evaluation, the changed balance between benefits and risks of COX-2 inhibitors in the ATC group M-01-AH means that the relation between prices and value of the treatment is no longer favourable from a cost-effectiveness point of view compared to conventional NSAID preparations.

Hence, the justification for general reimbursement is no longer present. In addition, mappings of the consumption pattern of selective COX-2 inhibitors in ATC group M-01-AH show that they are used frequently outside the approved indication, for example in short-term treatment of patients not suffering from arthritis.

Or they may be used as a first line agent, regardless that this is not rational (for instance for indications for which less expensive pain treatment would be a more rational choice).

Single reimbursement for selective COX-2 inhibitors

If patients suffer from arthritis and have a need for chronic pain treatment, it is possible for the doctor to apply for single reimbursement for a selective COX-2 inhibitor.

Certain conditions have to be fulfilled, for example that the patient is not treated with acetylsalicylic acid (aspirin~Mel) (ASA) and that an inexpensive pain-relieving medicinal product is not sufficient, cf. announcement on the website of Institute for Rational Pharmacotherapy (IRF) (link in fact box to the right).

The Danish Medicines Agency’s decision to remove selective COX-2 inhibitors from the positive list is made on the basis of a recommendation from the Reimbursement Committee, which is the Danish Medicines Agency’s medical scientific advisory body on reimbursement issues.

For further information please contact Karen Kolenda on tel.: +45 4488 9348.

Note 1: CHMP is the scientific Committee for Human Medicinal Products under the European Medicines Agency (EMEA)

Selective COX-2 inhibitors are newer products against arthritis, which were marketed in Denmark at the end of 1999 (Vioxx®), the middle of 2000 (Celebra) and the middle of 2003 (Arcoxia).

It is a pain-relieving medicine of the NSAID type, which may also be used for other kinds of pain than those caused by arthritis.

COX-2 inhibitors are up to 6 times more expensive than the NSAID preparations which they can replace in the treatment of arthritis.

The daily price of treatment with selective COX-2 inhibitors is DKK 10-12 (1.98 - 2.39 US), whereas the other NSAID preparations only cost DKK 2-3 (.40 - .59 US). Selective COX-2 inhibitors are not more effective than the older NSAID preparations.

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