Relapses During High-Dose Biotin Treatment in Progressive Multiple Sclerosis: a Case-Crossover and Propensity Score-Adjusted Prospective Cohort


High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Some reports have suggested that HDB treatment may be associated with an increased risk of relapse. We evaluate the relationship between exposure to HDB for treating PMS and the risk of relapse. We screened for PMS patients prospectively registered in a French regional cohort being part of the OFSEP national registry. In a case-crossover design among patients who received HDB, we first compared number of relapses before and after initiation of HDB. Second, time to the first clinical relapse was compared between patients who received HDB (biotin group) and a control group using a Cox survival analysis after a propensity score (PS) matching (1:1) and inverse probability of treatment weighting (IPTW) method. In the 42 PMS patients who received HDB, the number of relapses was statistically and clinically significant higher after biotin initiation than before biotin initiation (incident rate ratio [IRR] 7.4, 95% confidence interval [CI] 3.5–15.9, p < 0.0001). With the PS matching method, the risk of relapse was significantly higher in the biotin group compared to the control group (hazard ratio [HR] 4.3, 95% CI 1.4–13.3, p = 0.01). The IPTW method with 440 control patients revealed consistent results (HR 5.1, 95% CI 2.3–11.3, p < 0.0001). In our non-randomized study, HDB treatment for PMS was associated with an increased risk of relapse. The follow-up of PMS patients initiating HDB should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.

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High-dose biotin


Multiple sclerosis


Progressive multiple sclerosis


Annualized relapse rate


Propensity score


Inverse probability of treatment weighting


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Branger, P., Parienti, J., Derache, N. et al. Relapses During High-Dose Biotin Treatment in Progressive Multiple Sclerosis: a Case-Crossover and Propensity Score-Adjusted Prospective Cohort. Neurotherapeutics (2020).

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Key Words

  • Multiple sclerosis
  • relapses
  • biotin
  • progressive
  • propensity score