No clear benefit of hookworm treatment in people with relapsing multiple sclerosis

Last Updated: 2020-06-22

By Will Boggs MD

NEW YORK (Reuters Health) - Treatment with hookworm larvae, while safe and well tolerated, does not appear to reduce MRI evidence of progression in patients with relapsing multiple sclerosis (MS), although there is still uncertainty, according to new findings.

Earlier research had suggested gastrointestinal parasites might protect against the disorder. But placebo-controlled trials of helminth therapy in MS have been lacking, Dr. Cris S. Constantinescu of the University of Nottingham, in the UK, and colleagues write in JAMA Neurology.

The researchers undertook a phase-2 randomized, double-blind, placebo-controlled trial of hookworm treatment in 71 patients with relapsing MS. Infection with hookworm (Necator americanus) induces a mixed T-helper cell response, with Th2 and Treg-like dominance, and pilot trials have shown controlled infections to be safe in patients with asthma, allergic rhinoconjunctivitis and inflammatory bowel disease.

Overall, 66 patients completed the nine-month treatment period, and 61 patients completed the three-month safety follow-up.

At month 9, the cumulative number of new T2 lesions, newly enhancing lesions, or enlarging lesions, the primary efficacy endpoint, did not differ significantly between the hookworm group and the placebo group (154 vs. 164, respectively; P=0.19).

Eighteen patients (51%) treated with hookworm had no detectable MRI activity, compared with 10 placebo patients (28%).

"In terms of therapeutic effect, the most interesting/surprising finding was that a much higher number of patients receiving hookworm had no new disease activity on MRI," Dr. Constantinescu told Reuters Health by email. "While this reduced the power of our pre-set statistical test, it suggested a beneficial effect. Had we designed the study with a different outcome measure (proportion with no new disease activity, a measure increasingly looked at in MS) or adjusted the statistical analysis, the results would have been more powerful."

The percentages of T regulatory cells (of total CD4+ T cells) increased from screening to month 9 in the hookworm group and decreased in the placebo group.

Four patients (11.4%) in the hookworm group and 10 patients (27.8%) in the placebo group experienced relapses during the active period of the trial.

Absolute eosinophil counts increased in all but three hookworm patients, but did not change in the placebo group. Adverse events occurred with similar frequency in the two groups.

"I believe more studies are needed, in particular of longer duration with different outcome measures (clinical, and no new disease activity on MRI scans)," Dr. Constantinescu said. "If, as suspected, the effect is more modest than the current very potent disease-modifying treatments, then we need to think about who may best benefit without risking undertreating the disease."

"From the immunobiological and parasitological point of view, a positive surprise was that as few as 25 larvae, which were shown to cause very few side effects, induced a robust regulatory T cell response and eosinophilia (these may mediate a protective, inflammation-reducing effect), similar to that induced by natural infection with these parasites (where the parasite load is usually higher)," he added.

Dr. Daniel Ontaneda of Cleveland Clinic, in Ohio, who coauthored a linked editorial, told Reuters Health by email, "The most interesting finding is the shift in immunological patterns seen after treatment with hookworm. The primary outcome was also interesting, as it was negative despite the biological effect; this illustrates that MS is a complex disease and a set of biological measures does not explain the whole clinical picture."

"I think the main takeaway is that the trial supports the biology of the hygiene hypothesis and demonstrates hookworm infection can modulate the immune system," he said. "The second take-home is that hookworms probably are not a sufficiently effective treatment to treat MS alone."

SOURCE: https://bit.ly/2ADxWPv and https://bit.ly/2YbdkXK JAMA Neurology, online June 15, 2020.