Patients who are treated with natalizumab for multiple sclerosis (MS) risk reactivation of latent herpesvirus infections.1 Although this monoclonal antibody—which is approved for treatment of relapsing-remitting MS—is highly effective, its use has been associated with reactivation of at least 1 other latent virus (JC virus), leading to progressive multifocal leukoencephalopathy.
In addition, according to lead study author Nicoline Scheiss, MD, of the Johns Hopkins School of Medicine, Baltimore, Maryland, “anecdotally, we had seen that several of our patients had re-developed herpes labialis while on natalizumab therapy.” There have also been reports of patients with eruptions of shingles subsequent to treatment. Unlike JC virus, herpesviruses live in the periphery, in the nerve ganglia, but Dr Scheiss hypothesized that lymphocytes might also be blocked from entering the ganglia.
Patients and controls with latent herpesvirus infections were identified by questionnaire, based on whether they had ever had fever blisters. MS patients who did have herpesvirus infections were asked about the timing of blisters in relation to their natalizumab therapy. Because herpesvirus is shed in saliva, the authors also determined whether patients receiving natalizumab had increased salivary viral loads compared with MS patients who had not received natalizumab and persons without MS. They collected saliva specimens, as well as blood samples, just before and 1 week after natalizumab infusion, and quantified the level of virus in the samples.
Forty-four percent of MS patients and 38% of persons without MS had herpes labialis, in line with population-wide estimated prevalence rates. But MS patients were 3 times more likely to have eruptions each year than those without MS. MS patients were more than 4 times as likely to have virus in the saliva (46% vs 10%) and 5 times as likely to have virus in the blood (50% vs 10%). The viral load was also higher in MS patients. Among the MS patients, 40% had recurrences shortly after natalizumab therapy.
“There may be a remarkable reactivation of symptomatic and asymptomatic herpesvirus infections in MS patients treated with natalizumab,” Dr Scheiss concluded. Should patients receiving natalizumab therapy be more carefully screened for herpes outbreaks? “I think that depends on the severity of the infection,” Dr Scheiss said. She noted that many of the patients with recurrent outbreaks are already receiving prophylactic treatment.
1. Scheiss N, Zong J, Hayward G, Calabresi P, et al. Reactivation of herpes virus in multiple sclerosis patients on natalizumab therapy [P03.163]. Poster presentation, April 29, 2009.