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Background Risk factors in Multiple Sclerosis (MS) have been identified in samples that contain predominantly cases with relapse-onset MS (ROMS). It is unknown whether the risk factors differ in people with a progressive-onset MS (POMS). Methods The case-control study included 147 POMS cases, 264 ROMS cases and 558 community controls. Questionnaires were used to collect information on smoking, infections, breastfeeding and vitamin use in early life. Logistic regression was used to examine associations. Odds ratios (ORs) were adjusted for age, sex and latitude band. Results Compared with controls, POMS cases were more likely to have smoked ≥20 pack-years (AOR 2.83, 1.53-5.24) and ROMS cases were more likely to have ever been a smoker (AOR 1.48, 1.09-2.01). POMS cases (AOR 1.75, 1.05-2.93) and ROMS cases (AOR 1.74, 1.21-2.49) were both more likely to have had infectious mononucleosis. In childhood, POMS cases were less likely to use vitamin supplements (AOR 0.52, 0.30-0.91) or being breastfed (AOR 0.49, 0.31-0.79). Conclusions Smoking and infectious mononucleosis are associated with increased risk of both POMS and ROMS. Vitamin supplements in early life and being breastfed are associated with reduced risk of POMS, but there is no association in ROMS. Key messages POMS and ROMS share some commonly known risk factors. Some protective factors were identified in POMS that were not observed in ROMS.

1234Smoking, infectious mononucleosis, early-life exposures and risk of progressive-onset Multiple Sclerosis: a case-control study