JC virus or extended interval dosing? More data are needed

Dear Editor,

I read with interest the recent publication by Dalla Costa et al. ¹ titled “Neuroaxonal damage in natalizumab-treated MS patients: The role of JCV antibody titres.” In their study, the investigators reported that in John Cunningham virus (JCV) seropositive, multiple sclerosis (MS) patients treated with natalizumab, there appears to be subclinical neuroaxonal damage as measured by serum neurofilament light (sNfL) levels when compared to seronegative, natalizumab-treated MS patients. The association was also virus burden–dependent, with higher JCV index levels correlating with higher sNfL levels. While the investigators included some factors in their regression analysis, including age, sex, disability scoring, disease duration, and number of natalizumab infusions, they did not mention any information on the interval dosing schedule for the studied patients. The reader would assume that at least some JCV index-positive patients follow extended interval dosing, which is a crucial aspect that needs to be addressed. It is critical for the authors to provide such information and may want to repeat the analysis to control the interval dosing followed by each study patient. As the analysis stands at this time, one cannot rule out that the subclinical neuroaxonal damage is simply a factor of delayed dosing in some patients, perhaps following a 6-week or even longer interval between dosing, which is a common practice in many parts of the world including Italy. ²