Interferon-Beta-Induced Headache in Patients with Multiple Sclerosis: Frequency and Characterization

Background: Studies have shown that interferon-beta (IFN-β) treatment is associated with headaches in patients with multiple sclerosis (MS). Headaches can affect quality of life and overall function of patients with MS. We examined the frequency, relationships, patterns, and characteristics of headaches in response to IFN-β in patients with relapsing-remitting multiple sclerosis (RRMS).

Patients and methods: This study was a prospective, longitudinal analysis with 1-year follow-up. The study comprised 796 patients with RRMS treated with IFN-β (mean age 30.84±8.98 years) at 5 tertiary referral center outpatient clinics in Egypt between January 2015 and December 2017. Headaches were diagnosed according to the International Classification of Headache Disorders ICHD-3 (beta version), and data were collected through an interviewer-administered Arabic-language-validated questionnaire with an addendum specifically designed to investigate the temporal relationship between commencement of interferon treatment, and headache onset and characteristics.

Results: Two hundred seventy-six patients had pre-existing headaches, and 356 experienced de novo headaches. Of 122 patients who experienced headaches before IFN-β treatment, 55 reported headaches that worsened following onset of IFN-β treatment. In patients with post-IFN-β headaches, 329 had headaches that persisted for >3 months, 51 had chronic headaches, and 278 had episodic headaches, and 216 of these patients required preventive therapies. Univariate analysis showed a >6- and an approximately 5-fold increased risk of headache among those treated with intramuscular (IM) INF-β-1a (OR 6.51; 95% CI: 3.73-10.01; P-value <0.0001) and 44 μg of SC INF-β-1a (OR 5.44; 95% CI: 3.15-9.37; P-value <0.0001), respectively, compared with that in patients who received 22 μg of SC INF-β-1a.

Conclusion: Interferon-β therapy aggravated pre-existing headaches and caused primary headaches in patients with MS. Headache risk was greater following treatment with IM INF-β-1a and 44 μg SC INF-β-1a.