RRMS Drug Works by Shifting Anti-Inflammatory Immune Profile, Study Shows

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Researchers have found that changes in the composition of immune molecules — specifically, a shift to more anti-inflammatory cytokines and regulatory T-cells (Tregs) — likely account for the efficiency of alemtuzumab (Lemtrada) as a treatment for relapsing-remitting multiple sclerosis (RRMS).

The study, titled Alemtuzumab long-term immunologic effect: Treg suppressor function increases up to 24 months, appeared in the journal Neuroimmunology and Neuroinflammation.

Researchers led by Stefania De Mercanti at the University of Turin, Italy, investigated the immune profiles of 29 MS patients enrolled in the CARE-MS I and II trials comparing the efficacy of alemtuzumab to Refib (interferon beta-1a). The patients were followed for 24 months, and blood samples were collected at six-month intervals, starting before treatment onset and ending after two years of treatment.

Scientists looked at the gene expression profile of 26 immune-related molecules, including cytokines, chemokines and their receptors, as well as transcription factors. Researchers also determined the relative amounts of T-helper cell types Th1 and Th17, as well as Tregs and the activity of a Treg suppressor, MBP.

During the study, nine patients experienced 12 relapses. The study reported that the levels of anti-inflammatory cytokines, such as IL-10, IL-27, and TGF-β, continuously increased during the study, while all the pro-inflammatory molecules investigated decreased after six months of treatment and stayed low during measurements at all subsequent time points. The only exception was IL-22, which was elevated at 18 months but fell to low levels again at 24 months.

Alemtuzumab treatment also increased IL-2, a factor known to promote T-cell propagation, along with FoxP3, involved in the development and function of Tregs.

The team measured the amount of different types of T-cells and noticed that CD4+ type T-cells were decreased. Absolute numbers of Th1 and Th17 cells were also lower, although the team could not observe a reduction in the percentage of these cells. Th1 and Th17 are important mediators of RRMS pathology, whereas Tregs have an anti-pathogenic effect. The study reported that the percentage of Tregs was increased — a finding reflected in the Treg-mediated increased activity against MBP-specific Th1 and Th17 cells.

Interestingly, the team observed an increase in IL-17 producing cells and IL-2 gene expression in six patients who had a relapse around month 18.

In conclusion, the study showed that alemtuzumab treatment is associated with a change in the immune profile, promoting a more anti-inflammatory state in MS patients. The authors argued that the present findings, as well as a longer follow-up of the study, can provide valuable clinical information, including treatment timing and other relevant parameters.

Both alemtuzumab (Lemtrada) and Refib are approved by the U.S. Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis.

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