Minocycline reduces gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis.

We report a trial of minocycline in people with relapsingremitting multiple sclerosis (RRMS) that evaluates safety and estimates its effect on magnetic resonance imaging (MRI). Ten subjects with active RRMS received oral minocycline 100mg twice daily for 6 months after a 3-month run-in period. A 30-month treatment extension is ongoing. Clinical and laboratory assessments were completed at enrollment and then at 3-month intervals. MRI was performed at enrolment and then every 4 weeks. Patients without MRI activity during the run-in phase continued in the study, including completion of all MRI scans, to confirm lack of MRI worsening. The primary outcome was change in the mean number of gadolinium-enhancing lesions per scan during the first 6 months of treatment compared with the run-in period (Wilcoxon signed rank test, two-sided alpha of 0.05). Eighty percent of participants were women. Mean age was 42.8 years (SD 4.0). Mean MS duration was 11.8 years (SD 6.3). Median baseline extended disability status score (EDSS) was 2.5 (range 1.5–5.5). Mean relapse number in the two prior years was 2.6 (range 2–4). During the trial, there were no serious adverse events or laboratory abnormalities and no change in EDSS. Three relapses occurred during the run-in phase, five during the first 6-month treatment phase, and none during the following 6 months. On-treatment relapses included one associated with MRI enhancement (during month 1), two without enhancement (one scan was a postrelapse scan, and one scan was missed because the patient was taking steroids), and two mild truncal sensory attacks unassociated with MRI enhancement (both at 5 months). Mean total enhancing lesion number decreased from 1.38 lesions per scan during the run-in phase to 0.22 during the treatment phase (z 2.204, p 0.0276), representing a relative reduction of greater than 84%. During the run-in phase, 47.5% of MRI scans (19/40) were active, whereas 9.3% (5/54) were active during the minocycline phase. There were no active scans after month 2 (Fig) and no new active lesions after month 1. Although five patients accounted for all MRI activity before and after treatment, all patient data were included in all analyses. This study provides preliminary evidence that minocycline may be useful in MS and supports its safety. The MRI results are consistent with the ability of minocycline to inhibit matrix metalloproteinases, thus reducing lymphocyte access to the central nervous system. In addition, minocycline may have other beneficial properties including neuroprotection. Small sample size and short trial duration limit conclusions, but reduced MRI activity is encouraging and calls for definitive studies to establish minocycline efficacy in MS.