Revised public statement on Enbrel (etanercept) - Serious haematological reactions
News
The European Medicines Evaluation Agency's (EMEA) scientific committee, the Committee for Proprietary Medicinal Products (CPMP) has been made aware of 10 case reports of serious blood dyscrasias, some with a fatal outcome, in patients with rheumatoid arthritis treated with etanercept (Enbrel).
Etanercept (Enbrel)1 is a recombinant human tumour necrosis factor receptor that binds to and renders TNF biologically inactive. Enbrel is indicated in the treatment of active rheumatoid arthritis in adults when the response to disease modifying antirheumatic drugs, including methotrexate (unless contraindicated) has been inadequate and the treatment of active polyarticular-course juvenile chronic arthritis in children aged 4 to 17 years who have an inadequate response to, or who have proved intolerant of, methotrexate.
Since first marketing (USA, November 1998) an estimated 80,000 patients have been treated with the product world-wide but only a limited number is currently treated with this medicinal product within the EU (approx. 5500).
These 10 reports of serious blood dyscrasias, from world-wide post marketing experience, include 3 cases of aplastic anaemia and 7 cases of pancytopenia. Five (5) of these 10 cases had a fatal outcome due to sepsis. In the majority of these cases, there was a close temporal relationship between the start of treatment with etanercept and the occurrence of haematological disorders (range 2 weeks to 5 months). Since the clinical experience with etanercept is still limited as this product has only recently been marketed, onset after this period cannot be ruled out. Recent or concomitant exposure to other anti-rheumatic medicines known or suspected to have myelosuppressant effects, such as methotrexate, leflunomide, 6-mercaptopurine, cyclophosphamide and azathioprine was reported in some patients who subsequently developed pancytopenia; some patients had no clear past history of haematological abnormalities.
Following a review of the above information, the EMEA wishes to draw attention to the following:
- Cases of pancytopenia and aplastic anaemia, some with fatal outcome, have been reported rarely (i.e. less than 1 case out of 1,000 patients treated with the product) and very rarely (i.e. less than 1:10,000), respectively, in patients with rheumatoid arthritis treated with Enbrel.
- Caution should be exercised in patients with a previous history of blood dyscrasias being treated with Enbrel.
- All patients should be informed that if they develop signs and symptoms suggestive of blood dyscrasias or infections (e.g. persistent fever, sore throat, bruising, bleeding, paleness) whilst on Enbrel they should seek immediate medical advice.
- Such patients should be investigated urgently, including full blood count.
- If blood dyscrasias are confirmed, Enbrel should be discontinued.
As an urgent measure, the prescribing and patient information has been modified through a rapid procedure at the request of the marketing authorisation holder. The EMEA thought it necessary to provide this new information to the public. The complete revised product information is available in the European Public Assessment Report of Enbrel published on the EMEA website.
Update on demyelination disorders
The European Medicines Evaluation Agency's (EMEA) scientific committee, the Committee for Proprietary Medicinal Products (CPMP) has been made aware of 14 reports of demyelination disease in patients treated with etanercept (Enbrel).
The causal relationship between the onset of the neurological disorders and the administration of etanercept is unclear but some of the data present in the reports indicate a temporal association between starting etanercept and the onset of neurological disorders. Moreover, although no clinical trials have been performed evaluating etanercept therapy in patients with MS, two published studies investigating the effects of two other TNF inhibitors concluded that an inhibition of TNF in patients with established MS was likely to cause an exacerbation of their disease.
Following a review of the above information, the EMEA wishes to draw attention to the following:
- A careful risk/benefit evaluation is recommended when prescribing Enbrel to patients with pre-existing or recent onset of CNS demyelinating disease.
- Patients treated or likely to be treated with Enbrel with a current or previous history of a demyelinating disease (such as multiple sclerosis or optic neuritis) should inform their doctor.
The prescribing and patient information will be modified through a normal procedure at the request of the marketing authorisation holder.