Tetracycline Antibiotics

Experimental Medications: Other Therapeutic Strategies

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The tetracycline antibiotics, including minocycline and doxycycline, have immunomodulatory and neuroprotective activities. They appear to decrease the passage of lymphocytes across the blood-brain barrier. In 2009, a small double-blind, placebo-controlled Phase II trial of Copaxone plus minocycline showed favorable MRI data, with minocycline decreasing gadolinium-enhancing activity by 50 percent during a period of six months. A subsequent 24-month trial showed a significant decrease in lesion activity and clinical status.

A larger study called RECYCLINE enrolled 305 individuals with RRMS and used minocycline as an add-on to Rebif in people with RRMS. Data were presented at ECTRIMS in 2012, and disappointingly, minocycline did not provide significant improvement to either clinical or MRI outcomes.

Another Phase III trial conducted at 12 centers across Canada enrolled 142 people with a clinically isolated syndrome (CIS). The participants were randomized to oral minocycline at 100 mg twice daily or placebo. The primary endpoint of the study was conversion to multiple sclerosis within six months of randomization. Treatment was continued for up to two years, or until MS was confirmed. The risk for conversion to multiple sclerosis within six months after randomization was 33.4 percent in the minocycline group versus 61 percent in the placebo group, meaning that the antibiotic reduced the risk by almost one-half.

In analyzing the data, based on how many gadolinium-enhancing lesions the participants had on MRI at the start of the study, minocycline use still was associated with risk of conversion to MS at the six-month mark, but not by as great of a degree. At 24 months, no significant difference was seen between minocycline and placebo in terms of risk of conversion. Similarly, several MRI measures that were secondary outcomes of the study favored minocycline at six months, but not at 24 months. The rate of adverse events was higher among patients receiving minocycline than those on placebo (86.1 percent versus 61.4 percent), with hyperpigmentation, rash, nausea, dental discoloration, and dizziness found to be among the adverse effects experienced more often by individuals receiving the antibiotic. While the ultimate goal of treating CIS is to prevent conversion to MS, delaying conversion represents an important intermediate step toward that goal.57

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