Parasitic hookworm therapy had no significant benefit on MRI in patients with multiple sclerosis (MS), the phase II WIRMS trial showed.
Median cumulative numbers of new MRI lesions were not significantly different between MS patients who received Necator americanus larvae transcutaneously and those who received placebo, reported Cris Constantinescu, MD, PhD, of the University of Nottingham in England, and co-authors in JAMA Neurology.
However, about half of hookworm-treated participants and a quarter in the placebo group had no detectable MRI activity, they noted.
Hookworm also significantly increased T regulatory cell counts in peripheral blood. “The study shows that a single controlled exposure to a small number of hookworm larvae induces a lasting immunological response and some changes suggestive of a therapeutic effect,” Constantinescu said.
“This is the largest helminth therapy study in MS so far and the first randomized controlled trial,” he told MedPage Today. The choice of the helminth was carefully considered and this is the first trial using hookworm, he added.
The study stemmed from the hygiene hypothesis, a theory that postulates that exposure to certain parasitic infections may help protect against autoimmune or inflammatory diseases. In animal models of MS, helminth treatment appeared to be protective, noted Daniel Ontaneda, MD, PhD, and Jeffrey Cohen, MD, both of the Cleveland Clinic’s Mellen Center for Multiple Sclerosis, in an accompanying editorial.
Hookworm is a soil-transmitted helminth with a complex life cycle. Its larvae penetrate human skin, travel to the lungs, burrow through pulmonary alveoli, and migrate into the upper airway to the mouth where they are swallowed. They develop into adult forms after gaining access to the small intestine, producing “an indolent infection that can cause anemia, malnutrition, and pediatric cognitive delay,” Ontaneda and Cohen wrote.
In WIRMS, researchers administered hookworm larvae or placebo by direct skin contact to 71 participants with relapsing-remitting or secondary progressive MS from September 2012 to March 2016. Mebendazole, an antihelminthic agent, was given to patients who wanted to withdraw.
Mean age of the group was 45 and 71% were women. Participants were followed for 36 weeks, with a 12-week safety extension.
On the primary endpoint — the cumulative number of new or enlarging T2 lesions or newly enhancing lesions over 4 to 9 months post-infection — hookworm treatment showed no significant benefit (154 vs 164 lesions).
Eighteen of the patients treated with hookworm (51%) versus 10 patients treated with placebo (28%) had no detectable MRI activity. The higher rate of no detectable MRI activity in the hookworm group, while reducing the study power, suggested a treatment effect, the researchers said.
In immunologic studies, the percentage of CD4+/CD25high/CD127neg T cells increased at month 9 in the hookworm group (hookworm 4.4%; placebo 3.9%; P=0.01).
The study showed no significant differences in adverse events except that the hookworm group had more application-site skin discomfort (82% vs 28%). Serious adverse events in the hookworm group included type 1 diabetes in one patient and a hysterectomy for menorrhagia in another.
The results of this study need to be interpreted cautiously, Ontaneda and Cohen said. “The effect on the immune profile is interesting; however, this finding cannot be translated to evidence of clinical efficacy,” they wrote.
“Comparing helminth therapy with placebo was reasonable when this study was initiated in 2011 but would be difficult to justify today given the availability of robustly effective immunomodulatory therapies,” they added. “Conducting a trial with an active comparator group also would be difficult, as the efficacy of even the lowest potency available disease-modifying agents rival the effect of helminth treatment.”
The study had several limitations, the researchers noted. “A design and sample size calculation using the proportion of patients with no disease activity may be a better choice for an outcome measure,” they wrote. The 36-week treatment duration was short: a longer time of 1-2 years is needed to assess clinical response, they added.
“Although the potential therapeutic benefit of hookworm in MS is likely to be modest, in individual cases it may obviate or delay potent immunosuppressive treatment,” Constantinescu said. “The trial also allowed a number of ancillary studies, some of which are underway.”
Source: MedicalNewsToday.com
