Managing Wearing Off Effect in High-Efficacy Disease-Modifying Therapies


In this segment, Negroski comments on the realism behind wearing off effect of treatments, specifically ocrelizumab, and how clinicians may work around some of these issues.

At the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, NeurologyLive sat down with MS expert Donald Negroski, MD, to discuss several of the top presentations and data on treatment switches and aging in MS. Negroski provided an overview of various presentations, offering his clinical perspective and how findings may impact care going forward.

In this conversation, the MS expert gave commentary on a study examining "wearing off" effect in patients treated with ocrelizumab (Ocrevus; Genentech), an FDA-approved disease-modifying therapy for relapsing and progressive forms of the disease. He spoke on the findings, which highlighted alternative approaches that may alleviate some of this effect, and the frequency of wearing off seen in clinical settings.

Transcript edited below for clarity.

Donald Negroski, MD: This was extremely interesting. This study was out of University South Florida in Tampa, where they looked at their patients that were on an anti CD20 drug. In clinical practice, we all see this phenomenon where patients say that they can tell right before their next scheduled six-month infusion that something's different. They termed that "wearing off," and to better understand that, the investigators broke it down in much more detail. Usually the "wearing off" was within like two two to four weeks of their next scheduled dose. This was found in 25% of the patients, which is kind of interesting.

They further looked at the subtype of patients that were most likely to complain of wearing off, and those were patients that presented with symptoms of fatigue and high body index—more obese. And then the third one was those patients who self reported their disability on a scale to be moderate to severe. There was that kind of subgroup of patients that were kind of more attuned to complain of wearing off.

Then, the study authors either changed the frequency of treatment, maybe advancing it sooner, or changed the anti-CD20 drug to a different brand. And so by changing those two parameters, they noted that this wearing off phenomenon dropped dramatically. The trouble with infusing sooner than the scheduled is you run into payment [issues]. [Typically] the insurance won't pay for an earlier infusion, so you're kind of stuck to change the brand, basically. I thought that [presentation] was really interesting, because I think for neurologists that take care of patients with MS, especially with these infusible drugs, we always hear this kind of wearing off, and it's hard to get our mind around it. From a scientific standpoint, why does that happen? But we all see it. This study really shed some light on that.

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