Biotin in progressive multiple sclerosis

Evidence Summaries for Current Care Guidelines
Sari Atula

Level of evidence: D

The evidence is insufficient regarding the efficacy of biotin in progressive multiple sclerosis.

In a double-blind, placebo-controlled study «Tourbah A, Lebrun-Frenay C, Edan G ym. MD1003 (hig...»1 a total of 154 multiple sclerosis (MS) patients were randomized. They had either primary progressive MS (PPMS) or secondary progressive MS (SPMS). Inclusion criteria included baseline EDSS score of 4.5-7 and evidence of disease worsening within the previous 2 years to 12-month with clinical evidence of spastic paraparesis. Patients with clinical or radiological evidence of inflammatory activity within the previous year were excluded. They were randomized 2:1 to get 100 mg biotin or placebo three times a day for 12 months, followed by 12-month open biotin phase for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20 % decrease in timed 25-foot walk time compared with the best baseline result. The stratification was done only by the study center.

The randomization was not optimally balanced: 51,5 % of the biotin group and 58,8 % of the placebo group were women. The duration of MS was 14,8 years for the biotin and 17,4 years for placebo group. The rate of PPMS patients was 40,8 % in the biotin and 25,5 % in the placebo group. The same figures for SPMS were 59,2 % and 74,5 %, respectively. The mean age was 51 years and median EDSS was 6,0 for both groups. Concomitant immunomodulating product was used by approximately 40 % of the patients in both groups. Treatment with fampridine or amifampridine was used by 43,7 % of the biotin and 54,9 % of the placebo group.

A total of 13 (12.6 %; 95 % CI: 6.9 %–20.6 %) biotin-treated patients achieved the primary endpoint vs. none of the placebo-treated patients (p = 0.005). A total of 10 of the 13 (76.9 %) patients with reduced disability had 3-month confirmed improved EDSS scores and 5 (38.5 %) had improved TW25 times, while 2 (15.4 %) improved on both scores.

During the open 12-month follow up, 12 of the 91 (13.2 %; 95 % CI: 7.0 % – 21.9 %) patients initially treated with biotin had reduced MS-related disability at 18 months (confirmed at 24 months), including 10 of the 13 (77 %) patients who responded during the placebo-controlled phase. The safety profile of biotin was similar to that of placebo.

Comment: The quality of evidence is downgraded by study quality (unbalanced randomization), indirectness (short follow-up time) and by imprecise results (one small trial).

Clinical comment: It seems that the greater proportion of PPMS and lower proportion of SPMS patients were randomized to active treatment. This and other unbalances in randomization may partly be a confounding factor for the results.


  1. Tourbah A, Lebrun-Frenay C, Edan G ym. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study. Mult Scler 2016;22:1719-1731 «PMID: 27589059»PubMed