No symptom worsening
In the second study, the investigators further examined changes in symptom burden related to the amount of time from ocrelizumab infusion. They evaluated 110 patients, aged 18-80 (mean age 44.8) who had Expanded Disability Status Scale (EDSS) scores between 0-7. Study participants were either initiating ocrelizumab or had been on the drug for at least 1 year.
Symptom burden was evaluated with the Neurological Disorders (Neuro-Qol) questionnaire and SymptoMScreen patient-reported outcomes at the beginning of the study at week 4, and near the end of the ocrelizumab infusion cycle, at week 22.
The researchers found that among 69 participants who completed the questionnaires, there were no significant differences at week 22 versus week 4 across a wide range of symptoms, including walking, spasticity, pain, fatigue, cognitive function, dizziness, and depression between the two timepoints.
The only change on the Neuro-QoL score was in the sleep disturbance domain, which improved marginally at the end of the cycle (P = .052). This study did not evaluate changes in B-cells.
Dr. Katz noted that the inclusion of patients over age of 55 in the study offered important insights.
“Our hypothesis was that we were going to start seeing a higher rate of complications, especially infections, in people who are older and may be at a higher risk of infection and disability,” Dr. Katz noted. “But so far, we haven’t seen any higher risk in older patients or those with more disability than anyone else, which is good news.”
Amplification of baseline symptoms not uncommon
Commenting on the research, Scott D. Newsome, DO, current president of the CMSC, noted that although no association was observed between the B-cell repletion and symptoms, amplification of flare-up symptoms that are linked to B-cell depleting therapy infusion timing are not uncommon.
“The ‘wearing-off’ phenomenon is not unique to the B-cell therapies,” said Dr. Newsome, who is also director of Johns Hopkins University’s Neurosciences Consultation and Infusion Center and an associate professor of neurology at the JHU med school. “With natalizumab (Tysabri), patients can have an amplification of baseline symptoms as they come closer to their next infusion, and it has been speculated that maybe it was something biologically happening, such as inflammatory cytokines ramping back up or some other mechanisms.”
“Now that we have the B-cell depleting therapies, we tend see the same kind of pattern, where a few weeks leading up to the next infusion, people will develop these amplified symptoms,” he said.
The possibility of a cumulative effect, appearing to address the B-cell repletion associated with early infusions, could have implications over time, Dr. Newsome noted.
“This is important because if people are going on these therapies long-term, the question we may need to ask is whether they actually need to continue to get an infusion every 6 months,” he said.
As these questions around the safety of long-term immunosuppressant drug use continue, different dosing regimens may need to be considered in order to mitigate potential infection risk, he added.
Dr. Katz reports consulting and/or speakers’ bureau relationships with Alexion, Biogen, EMD Serono, Genentech, Novartis, and Sanofi. Dr. Newsome reports relationships with Autobahn, BioIncept, Biogen, Genentech, Novartis, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, and MedDay Pharmaceuticals.
A version of this article first appeared on Medscape.com.