The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study.

Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment. Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS.

The effect of immunomodulatory treatment on multiple sclerosis fatigue.

OBJECTIVE: To assess the effects of glatiramer acetate and beta interferon on fatigue in multiple sclerosis. METHODS: Fatigue was measured at baseline and six months using the fatigue impact scale (FIS). Groups (glatiramer acetate and beta interferon) were evaluated for the proportion improved, using Fisher's exact test. Logistic regression analysis assessed the relation between treatment group and improvement and controlled for confounding variables. RESULTS: Six month paired FIS assessments were available for 218 patients (76% female). Ages ranged between 19 and 61 years, with 86% having relapsing-remitting disease. Glatiramer acetate was used by 61% and beta interferon by 39%. At baseline, total FIS and subscale scores were comparable in the two groups. More patients improved on glatiramer acetate than on beta interferon on total FIS (24.8% v 12.9%, p = 0.033; adjusted odds ratio = 2.36, 95% confidence interval 1.03 to 5.42), and on physical (28.6% v 14.1%, p = 0.013) and cognitive subscales (21.1% v 10.6%, p = 0.045). Logistic regression analysis confirmed the association between glatiramer acetate use and improved fatigue, after accounting for baseline group differences. CONCLUSIONS: The odds of reduced multiple sclerosis fatigue were around twice as great with glatiramer acetate treatment as with beta interferon. Confirmation of this result is required.