Malignant Hypertension in Patients Using Interferon Beta-1a for MS

Patients taking Rebif (interferon beta-1a) may ask specialty pharmacists about recent reports of an increased risk of malignant hypertension with this specific formulation of interferon beta-1a.

According to a March 27 editorial in the New England Journal of Medicine, use of a certain formulation of Rebif, a specific brand of interferon beta-1a manufactured by Merck, may lead to rare cases of hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura (HUS/TTP).^1,2

In HUS, red blood cells are hemolyzed and the resulting hemolysis of blood cells may then result in the formation of numerous blood clots throughout the body. Clotting, in turn, may lead to severe or malignant hypertension.^1,2

Although the chance of developing HUS is very small, patients with relapsing-remitting multiple sclerosis (MS) who take Rebif (interferon beta-1a) subcutaneously 3 times weekly may ask about the potential for this adverse event.

In South Scotland, between 2010 and 2012, investigators reported that 4 patients with multiple sclerosis who were using Rebif experienced malignant hypertension with signs of thrombotic microangiopathy. Although 6 additional cases of HUS/TTP were found in the United Kingdom from 1998 to 2013 through a broader search of drug safety databases, the common element among all 4 patients in South Scotland was the use of Rebif.

Although Merck added a warning to the Rebif package insert in April 2009, investigators traced the 4 cases to 10 specific batches of Rebif, which suggests that the cases of malignant hypertension may be related to manufacturing concerns. A search of drug safety data revealed that significantly more cases of HUS/TTP occur in countries using the Rebif formulation of interferon beta-1a than in countries using other formulations of interferon beta-1a (P = .02).^1,3

It is important to note that the risk of HUS/TTP is very small, and patients should not stop using maintenance treatments as prescribed based on a new concern about a very rare adverse event. It is also important to remind patients that the formulation of Rebif used in Scotland is slightly different from the formulation used in the United States, and that the results of this study do not necessarily apply to the US supply of Rebif.²

Treatments like Rebif reduce the risk for relapses of MS. However, from a drug safety perspective, it is important for health care professionals to remain vigilant when patients with MS taking Rebif present with severe hypertension, as the hypertension may be a result of clot formation induced by HUS/TTP.^1-3

Report cases of severe hypertension occurring with Rebif by calling the FDA’s MedWatch program at 1-800-FDA-1088. Reporting these incidents may help trace the source of the potential manufacturing issue that some scientists believe may be related to these rare, but serious adverse events.^1-3

References:

• Hunt D, Kavanagh D, Drummond I, et al. Thrombotic microangiopathy associated with interferon beta. N Engl J Med. 2014;370(13):1270-1271.
• Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int. 2001;60(3):831-846.
• 3. Rebif (interferon beta-1a) [package insert]. Rockland MA: EMD Serono Inc; 2013.