HSA would like to update healthcare professionals on overseas cases of thrombotic microangiopathy (TMA) and nephrotic syndrome that have been reported with the use of interferon beta products.
Interferon beta products have been registered locally since 1999 under the brands Rebif® (interferon beta-1a, Merck Pte Ltd) and Betaferon® (interferon beta-1b, Bayer (South East Asia) Pte Ltd). Rebif® is approved for the treatment of relapsing multiple sclerosis (for both 22mcg/0.5mL and 44mcg/0.5mL strengths) and treatment of patients with a single demyelinating event with an active inflammatory process, who are determined to be at high risk of developing relapsing multiple sclerosis (for 44mcg/0.5mL strength only). Betaferon® is also approved for the above two indications, as well as for the treatment of secondary progressive multiple sclerosis with active disease.
Post-marketing cases of TMA and nephrotic syndrome
Overseas post-marketing cases of TMA, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with the use of interferon beta products. In October 2014, the UK Medicines and Healthcare Products Regulatory Agency issued a drug safety update on a cluster of reports of TMA that occurred with interferon beta.1 A total of 13 reports of TMA, TTP and/or HUS were received by the Agency. Clinical features of TMA include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g., confusion and paresis) and impaired renal function.
Overseas cases of nephrotic syndrome with different underlying nephropathies have also been reported in patients treated with interferon beta. Early signs and symptoms of nephrotic syndrome include oedema, proteinuria and impaired renal function, especially in patients at high risk of renal disease.
Both TMA and nephrotic syndrome may develop several weeks to several years after starting treatment with interferon beta.
Review by the European Medicines Agency (EMA)
The Pharmacovigilance Risk Assessment Committee (PRAC) of the EMA conducted a review on the risk of TMA and nephrotic syndrome associated with the use of interferon beta products in September and May 2013, respectively. In February 2014, PRAC concluded that a causal association between interferon beta products and TMA and nephrotic syndrome could not be ruled out.2,3 Consequently, their product labels were updated and a Dear Healthcare Professional Letter was issued to communicate these safety issues to healthcare professionals in the EU.
Local situation and HSA’s advisory
HSA has not received any local adverse reaction reports of TMA and nephrotic syndrome associated with the use of interferon beta products. The local package inserts of Rebif® and Betaferon® have been strengthened to include warnings on the risk of these safety concerns.
Healthcare professionals are advised to monitor and consider the possibility of TMA and nephrotic syndrome in patients treated with interferon beta products, if signs and symptoms consistent with these diagnoses are identified.
References
- http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON462300
- http://www.ema.europa.eu/docs/en_GB/document_library/PRAC_recommendation_on_signal/
2014/02/WC500162042.pdf
- http://www.ema.europa.eu/docs/en_GB/document_library/Minutes/2014/03/WC500163384.pdf