The Rise and Fall of High-Dose Biotin to Treat Progressive Multiple Sclerosis
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COMMENTARY
The Rise and Fall of High-Dose Biotin to Treat Progressive Multiple Sclerosis Carolyn H. Goldschmidt 1 & Jeffrey A. Cohen 1
# The American Society for Experimental NeuroTherapeutics, Inc. 2020
Key Words Biotin . multiple sclerosis . progressive MS . MS relapse
Currently, effective treatments for patients with progressive multiple sclerosis (PMS) are an unmet need. Pivotal trials of ocrelizumab in primary progressive MS (PPMS) and siponimod in secondary progressive MS (SPMS) demonstrated efficacy, but the magnitude of benefit was modest and appeared to be predominantly in participants with recent or ongoing focal lesion activity [1, 2]. Biotin is a co-factor for four essential carboxylases expressed in oligodendrocytes and neurons. Administration of high-dose biotin (HDB) has been hypothesized to promote myelin repair and protect against virtual hypoxia-driven axonal degeneration and, as a result, might represent a novel treatment strategy for PMS [3]. A small, open-label pilot study of HDB in PMS showed clinical disability improvement measured as decrease in the Expanded Disability Status Scale (EDSS) [4]. In the randomized, double-blind, placebo-controlled MS-SPI trial, which enrolled 154 participants with PP or SP MS, 13 of 103 (12.6%) participants treated with HDB demonstrated disability reversal, measured as improved EDSS or timed 25-ft walk (T25FW) at 9 months and confirmed at 12 months, compared to 0 of 51 of participants treated with placebo [3]. HDB appeared well-tolerated and safe. An important point raised in this trial, however, was interference with certain laboratory tests in patients taking HDB. There were 11 cases of apparent hyperthyroidism (low thyroid-stimulating hormone) in patients taking HDB, which was determined to be due to biotin interference with laboratory tests that utilize biotinylated antibodies. Besides thyroid-stimulating hormone, other common tests sensitive to interfere by HDB include tests for vitamin D, creatine kinase, troponin, and prostate specific antigen [5]. * Jeffrey A. Cohen [email protected] 1
Mellen Center U-10, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA
In MS-SPI, MS relapses occurred in 4.9% of participants in the HDB-treated group and 7.8% of the placebo group during the initial double-blind phase, and in 7.7% of the HDB-treated participants and 4.8% of the placebo participants in the extension phase. However, MRI scans performed at month 12 detected new lesions in 23.4% of HDB-treated participants and 13% of placebo-treated participants; 8.5% of HDB-treated participants had enlarging lesions and 4.3% had at least one gadolinium-enhancing lesion compared to no placebo-treated participants. These MRI changes were unanticipated and raised concern about potential pro-inflammatory effects of HDB. The results of a second phase 3 trial of HDB in PMS, SPI2, recently were presented [6]. The primary endpoint of this 27month study was proportion of participants with improvement of disability at month 12 confirmed at month 15 measured as improveme
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