Stroke, Adverse Events Risk Heightened by MS Interferon-beta Treatment

JULY 07, 2017
Kenneth Bender
There is a heightened risk of stroke associated with interferon-beta (IFN-B) treatment of multiple sclerosis (MS), according to a recent large, long-term study of patients in a naturalistic setting.
Along with stroke, IFN-B patients are more susceptible to adverse events that have been previously found in clinical trials, including migraine, hematologic abnormalities and depression, according to this study.
Helen Tremlett (pictured), PhD, of the Centre for Brain Health, Vancouver, BC, and colleagues found in research indication that IFN-Bs have been modestly effective as first-line therapy for relapsing-remitting multiple sclerosis (RRMS), and considered generally safe — particularly when compared to newer, disease-modifying treatments for MS. 
They note, however, that there has been little systematic assessment of their safety in real-word clinical practice.
"By presenting an extensive risk profile of the IFN-Bs, our findings provide new insights into the benefit-risk ratio of the IFN-Bs in the real-world setting," Tremlett and colleagues wrote.  "Our findings complement and extend those observed in clinical trials and provide new evidence that IFN-B is associated with stroke."
The researchers identified 1,031 patients with RRMS who had received treatment with an IFN-B at a British Columbia clinic between 1995-2004, and followed their course through 2008, or until death or exposure to a non-IFN-B disease-modifying agent.
The association of an adverse event with IFN-B treatment was detected through a nested case-control analysis, with a calculation of the potential of occurrence in at least 30 cases, and comparison to age- and sex- matched controls. The mean duration of follow-up was 8 (±3.8 Standard Deviation) years.

The researchers reported that exposure to IFN-B was associated with a 1.8-fold increased risk of stroke, a 1.6-fold increased risk of migraine, and a 1.3-fold increase in risk of depression and of hematologic abnormalities. Odds ratios, calculated with conditional logistic regression and adjusted for age at study entry, for stroke was 1.83 (95% Confidence Interval 1.16-2.89), for migraine 1.55 (1.18-2.04), for depression 1.33 (1.13-1.56), and for hematologic abnormalities 1.32 (1.01-1.72).
Prior to this study, Tremlett and colleagues indicated any link between stroke and IFN-B treatment was based on a few case reports.  They suggest that a causal association is biologically plausible, however, as the treatment may alter neuron wall competence or provoke a histocompatibility cascade to enhance platelet adhesion to the endothelium.
The other adverse events, which have emerged in clinical trials, also have some rationale from preclinical studies, researchers noted. They suggest the risk of migraine may be increased by activation of interleukin-10 expression, which has been implicated in the pathogenesis of migraine. 
Hematologic abnormalities such as leukopenia and lymphopenia could arise from the immunomodulatory properties of IFN-B, according to the study, and anemia from an increase in cytokine release which may provoke  hematopoietic inhibitory responses.
The study also detected a reduced risk of bronchitis and upper respiratory infections after at least 2 years of IFN-B treatment. This could reflect the previously demonstrated antiviral effects of the agent, researchers noted.
The study, "Evaluating the safety of B-interferons in MS," was published online in the June issue of Neurology.
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