Dimethyl fumarate (Tecfidera): fatal PML in an MS patient with severe, prolonged lymphopenia
- Medicines and Healthcare products Regulatory Agency
- 30 March 2015
- Therapeutic area:
- Dermatology, Immunosuppression and transplantation, and Neurology
Check full blood counts before prescribing dimethyl fumarate and then every 6 to 12 months. Stop treatment immediately if you suspect progressive multifocal leukoencephalopathy.
Post-publication note: this article has been superseded. See updated information published in April 2016 for the latest advice.
Before prescribing dimethyl fumarate:
- ensure that the full blood count (including lymphocytes) has been checked - note that dimethyl fumarate has not been studied in patients with pre-existing lymphopenia or in combination with other immunosuppressive medicines
- explain the risk of lymphopenia and potential risk of progressive multifocal leukoencephalopathy (PML) to patients and carers – see Information to give to patients and carers
During dimethyl fumarate treatment:
- monitor patients - check full blood counts, including lymphocytes, every 6 to 12 months or more frequently if clinically indicated
- monitor patients with lymphopenia closely for features of PML (eg signs and symptoms of neurological dysfunction) and other opportunistic infections
- stop dimethyl fumarate treatment immediately and investigate appropriately if you suspect PML
- consider that PML can present with similar features to multiple sclerosis because PML is also a demyelinating disease
- continue to report suspected adverse drug reactions to dimethyl fumarate or any other medicine on a Yellow Card
Dimethyl fumarate is licensed to treat relapsing remitting multiple sclerosis in adults. Dimethyl fumarate can cause severe lymphopenia: lymphocyte counts decreased by approximately 30% from baseline values during treatment in clinical trials.
PML case details
A fatal case of PML was reported in Germany in October 2014 in a patient participating in the open-label ENDORSE study of dimethyl fumarate in multiple sclerosis. The patient received dimethyl fumarate for 4.5 years and experienced severe lymphopenia for more than 3.5 years.
This is the only known case of PML associated with dimethyl fumarate in a multiple sclerosis patient to date. Cases of PML have been reported with the use of fumaric acid esters (including dimethyl fumarate) in lymphopenic patients with psoriasis. However, in some of these cases, it could not be confirmed that the treatment caused PML (eg other risk factors for PML may have been present).
PML and multiple sclerosis symptoms can be similar
PML can present with similar features to multiple sclerosis as both are demyelinating diseases.1 Advise patients to consult their prescriber if they notice any new, unusual or worsening symptoms.
Unlicensed use of dimethyl fumarate for psoriasis
Medicines containing dimethyl fumarate and other fumaric acid esters are not licensed in the UK for use in psoriasis. However, we are aware that these medicines are sometimes imported as ‘specials’.2 If you are considering such use, be aware of the risks of severe, prolonged lymphopenia and serious opportunistic infections.
The licence-holder is working with the European Medicines Agency to evaluate the evidence for the risk of PML and to consider changes to the prescribing information. We will communicate any new advice for healthcare professionals as soon as it is finalised.
NICE guidance TA320 – Dimethyl fumarate for treating relapsing-remitting multiple sclerosis
NICE evidence search – Fumaderm: what is the evidence for its efficacy and safety in treating psoriasis?
Article citation: Drug Safety Update volume 8 issue 8 March 2015: 1
Ludwig Kappos and others. ‘Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring’ Lancet Neurology 2011: volume 10, pages 745-758 (viewed on 30 March 2015) ↩
Published: 30 March 2015