PT  - JOURNAL ARTICLE
AU  - Carlo Pozzilli
AU  - Laura De Giglio
AU  - Valeria T. Barletta
AU  - Fabiana Marinelli
AU  - Floriana De Angelis
AU  - Valentina Gallo
AU  - Veronica A. Pagano
AU  - Stefano Marini
AU  - Maria C. Piattella
AU  - Valentina Tomassini
AU  - Patrizia Pantano
TI  - Oral contraceptives combined with interferon β in multiple sclerosis
AID  - 10.1212/NXI.0000000000000120
DP  - 2015 Aug 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e120
VI  - 2
IP  - 4
4099  - http://nn.neurology.org/content/2/4/e120.short
4100  - http://nn.neurology.org/content/2/4/e120.full
SO  - Neurol Neuroimmunol Neuroinflamm2015 Aug 01; 2
AB  - Objective: To test the effect of oral contraceptives (OCs) in combination with interferon β (IFN-β) 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-β-1a subcutaneously (SC) only (group 1), IFN-β-1a SC plus ethinylstradiol 20 μg and desogestrel 150 μg (group 2), or IFN-β-1a SC plus ethinylestradiol 40 μg and desogestrel 125 μg (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-β 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-β plus ethinylstradiol and desogestrel decreases the cumulative number of active brain MRI lesions compared with IFN-β alone.AE=adverse event; ARR=annualized relapse rate; CI=confidence interval; CUA=combined unique active; EAE=experimental autoimmune encephalomyelitis; EDSS=Expanded Disability Status Scale; Gd=gadolinium; IFN=interferon; IL=interleukin; ITT=intention to treat; MS=multiple sclerosis; OC=oral contraceptive; RA=rheumatoid arthritis; RRMS=relapsing-remitting MS; SC=subcutaneous; tiw=3 times a week