Unanswered Questions About MS Therapies
In an interview, Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates, New York, who was not involved in the study, emphasized the importance of high-potency DMTs and adherence for treatment success.
“Lower-efficacy DMT might result in insufficient suppression of disease activity that might not be clinically apparent,” he said. “Routine examination is not sufficient to detect cognitive impairment or change in cognitive impact of disease. Adherence is critical to therapy success, and infusion therapies or treatment not self-administered have higher likelihood of higher adherence rates.”
Commenting on the study by Piehl et al, Dr. Gudesblatt said it “provides important real-world information” on how infusion therapies are tolerated, their effectiveness, and their adherence compared with oral or self-administered treatments. For rituximab, “just as importantly, this therapy provides effective disease control with less accumulated disability and disability related health care costs,” he said.
Dr. Gudesblatt said there are several unanswered issues in the study, including the uncertain nature of the incidence and development of rituximab-blocking antibodies, which could potentially differ by biosimilar. “[H]ow this impacts therapy efficacy is unclear,” he said. “The presence of blocking antibodies should be routinely monitored.”
Another issue is the between-patient variation in degree of B-cell depletion and speed of B-cell repletion, which might differ based on therapy duration. “The timing and frequency of dosing is an issue that also needs further critical analysis and improved guidelines,” he noted.
Dr. Gudesblatt said up to 25% of patients with MS might have unrecognized immune deficiency. “[I]mmune deficiency unrelated to DMT as well as the development of immune deficiency related to DMT are issues of concern, as the rate of infections in B-cell depleting agents are higher than other class of DMT,” he explained. Patients with MS who develop infections carry significant risk of morbidity and mortality, he added.
“Lastly, the issue of vaccination failure is extremely high in B-cell depleting agents, and with the recent viral pandemic and lingering concerns about recurrent similar scenarios, this is another issue of great concern with use of this highly adherent and effective DMT choice,” Dr. Gudesblatt said.
Several authors reported personal and institutional relationships in the form of grants, consultancies, research support, honoraria, advisory board positions, travel support, and other fees for Bayer, Biogen, Merck, Novartis, Roche, and Teva. Dr. Gudesblatt reports no relevant conflicts of interest.