Oral contraceptives combined with interferon beta in multiple sclerosis

Objective: To test the effect of oral contraceptives (OCs) in combination with interferon beta (IFN-beta) on disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: One hundred fifty women with RRMS were randomized in a 1: 1: 1 ratio to receive IFN beta-1a subcutaneously (SC) only (group 1), IFN-beta-1a SC plus ethinylstradiol 20 mu g and desogestrel 150 mg (group 2), or IFN-beta-1a SC plus ethinylestradiol 40 mg and desogestrel 125 mg (group 3). The primary endpoint was the cumulative number of combined unique active (CUA) lesions on brain MRI at week 96. Secondary endpoints included MRI and clinical and safety measures. Results: The estimated number of cumulative CUA lesions at week 96 was 0.98 (95% confidence interval [CI] 0.81-1.14) in group 1, 0.84 (95% CI 0.66-1.02) in group 2, and 0.72 (95% CI 0.53-0.91) in group 3, with a decrease of 14.1% (p = 0.24) and 26.5% (p = 0.04) when comparing group 1 with groups 2 and 3, respectively. The number of patients with no gadolinium-enhancing lesions was greater in group 3 than in group 1 (p = 0.03). No significant differences were detected in other secondary endpoints. IFN-beta or OC discontinuations were equally distributed across groups. Conclusions: Our results translate the observations derived from experimental models to patients, supporting the anti-inflammatory effects of OCs with high-dose estrogens, and suggest possible directions for future research. Classification of evidence: This study provides Class II evidence that in women with RRMS, IFN-b plus ethinylstradiol and desogestrel decreases the cumulative number of active brain MRI lesions compared with IFN-b alone. Neurol