COPENHAGEN—In patients with multiple sclerosis (MS), IV immunoglobulin (IV Ig) infusions increase John Cunningham virus (JCV) antibody levels, which may result in seropositivity, according to a study presented at the 29th Congress of the European Committee for Treatment and Research in MS (ECTRIMS). This finding suggests that risk stratification rules based on JCV antibody status may not apply to patients recently treated with IV Ig.
The concentration of JCV antibodies is likely to decrease over time after IV Ig is discontinued. “The lack of consistent sampling in our patients prevents us from making firm conclusions as to the likelihood of return to innate (pre–IV Ig) JCV antibody levels after stopping IV Ig,” said Ilya Kister, MD, Assistant Professor of Neurology at New York University School of Medicine in New York City. He and his colleagues are investigating whether age, IV Ig therapy duration, JCV antibody concentration during IV Ig therapy, and time from IV Ig administration to JCV antibody testing affect JCV antibody concentration after IV Ig discontinuation.
The STRATIFY Trial
Dr. Kister and colleagues examined data for 102 patients with MS who participated in the STRATIFY-2 trial and had monthly infusions of IV Ig (0.7 g/kg) at any point during the trial. The researchers also analyzed results from the commercial STRATIFY JCV and STRATIFY JCV Dx SELECT assays for participants in STRATIFY-2 who had been exposed to IV Ig. The team calculated the relative concentration of polyclonal JCV antibodies as JCV monoclonal antibody equivalents by interpolating the optical density or index values for each sample against a reference curve prepared using a monoclonal antibody to JCV.
JCV Antibody Levels Decreased Over Time
Of the 1,251 patients enrolled in STRATIFY-2, 1,143 were not exposed to IV Ig, and 58% of these patients were seropositive for JCV antibody. In contrast, all 71 STRATIFY-2 enrollees who were tested for JCV antibodies within 30 days of IV Ig administration were seropositive. Sixteen of 25 (64%) STRATIFY-2 enrollees who were exposed to IV Ig more than 30 days after IV Ig administration were seropositive, which suggests that the level of JCV antibodies in IV Ig–exposed patients declines over time.
The median relative concentration of JCV antibodies was 0 µg/mL for patients not yet exposed to IV Ig. For patients receiving IV Ig, the median relative concentration of JCV antibodies was approximately 2 µg/mL. At 30 days after IV Ig exposure, the median relative concentration of JCV antibodies was less than 1 µg/mL.
The researchers observed a significant decrease or complete elimination of JCV antibody relative concentrations for many samples after discontinuation of IV Ig, which implies a reduction of passively transferred JCV antibody levels over time. “However, without pre–IV Ig samples, it is not possible to determine if subjects return to baseline levels or not,” said Dr. Kister.
—Erik Greb