Doxycycline may be effective as adjunct to antiseizure treatment for nodding syndrome

Key takeaways:

• The study included 240 patients with nodding syndrome given doxycycline or placebo.
• Doxycycline may help reduce severe morbidity and the number of potentially fatal complications in certain individuals.

Doxycycline was safe and may be effective as adjunctive therapy to antiseizure medication in young people with nodding syndrome, according to research from Lancet Global Health.

“Despite multiple studies of environmental, metabolic, infectious, toxic and genetic factors, the etiology of nodding syndrome remains undetermined,” Richard Idro, PhD, MBChB, MMED, an associate professor of pediatrics and pediatric neurology in the College of Health Sciences at Makerere University in Kampala, Uganda, and colleagues wrote.

Nodding syndrome is a little-known neurological disorder in which children develop episodes of head nodding. It affects about 10,000 children in Africa.

Idro and colleagues attempted to assess the efficacy of doxycycline to treat nodding syndrome, based on the hypothesis that it is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus (O-volvulus) or its Wolbachia symbiont.

They conducted a randomized, double-blind, placebo-controlled, phase 2 trial, recruiting 329 young persons between September 2016 and August 2018. From this initial cohort, 240 enrollees (58% boys; median age 16 years; median duration of symptoms, 9 years) aged 8 to 18 years with nodding syndrome were included from districts affected by the condition in northern Uganda.

Participants were admitted to Kitgum General Hospital in Kitgum, Uganda, for 1 to 2 weeks for baseline testing and antiseizure medication tracking, where they were randomized 1:1 to receive either 100 mg doxycycline or placebo daily for 6 weeks. Diagnoses of O-volvulus and antibodies to host neuronal proteins (HNPs) were made using luciferase immunoprecipitation system assays and immunohistochemistry. Idro and colleagues subsequently clinically re-evaluated all participants at 6, 12, 18 and 24 months. At 24 months, participants were again admitted to Kitgum where pre-randomization procedures were repeated.

The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. Secondary outcomes included recorded change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O-volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom and overall quality of life; disease severity at 24 months; incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months.

Baseline analyses determined 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs.

According to results, at 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseline. Six weeks of doxycycline had no effect on concentration of autoantibodies to HNPs, seizure control, disease severity or quality of life at the 24-month follow-up, but substantially decreased Ov16 antibody concentrations.

Acute seizure-related hospitalizations (rate ratio [RR] = 0.43; 95% CI, 0.2–0.94) and deaths (RR = 0.46; 95% CI, 0.24-0.89) were significantly lower in the doxycycline group. At 24 months, 96 (84%) of 114 participants who received doxycycline tested positive for antibodies to Ov16, compared with 97 (87%) of 111 given placebo. A total of 74 (65%) participants on doxycycline tested positive for antibodies to OVOC3261, compared with 57 (51%) from the placebo group.

There were no recorded differences in the incidence of grade 3 to 5 adverse events across the two groups, the researchers additionally reported.

“In these individuals, treatment with doxycycline might help reduce severe morbidity and the number of potentially fatal complications,” Idro and colleagues wrote.