Background: The relationship between multiple sclerosis (MS) and headache (HA) is not well known. It was reported that interferon-beta (IFNβ) could induce or worsen HA.

Objective: To evaluate the impact of IFNβ treatment on HA and the relationship between HA and the various commercial preparations of IFNβ in mildly disabled patients with MS.

Methods: A specific questionnaire was administered to 357 relapsing-remitting MS patients. Characteristics of HAs were considered, including the temporal relationships with IFNβ administration.

Results: One hundred and seventeen patients were treated with weekly intramuscular injections of interferon IFNβ-1a (Avonex(®)), 84 with subcutaneous injections of IFNβ-1b (Betaferon(®)) every other day, 48 and 108 with three times weekly subcutaneous injections of IFNβ-1a (Rebif(®)) 22 mcg or IFNβ-1a (Rebif(®)) 44 mcg, respectively. Three hundred and fourteen patients were affected by HA, and among them, 219 patients suffered of pre-existing HA. In this latter group, 121 subjects (55%) noted a worsening of their HA after starting IFNβ therapy; this was more frequently reported by patients treated with Avonex(®) and Rebif(®) 44. Ninety-five patients experienced new HA.

Conclusions: IFNβ treatment could worsen HA in patients with pre-existing HA or cause the appearance of new HA. Among different IFNβ preparations, Rebif(®) 44 and Avonex(®) seemed to be more cephalalgic than the other drugs.