Patients on B-cell therapies less likely to stop treatment: Study
Lack of efficacy among reasons for people discontinuing oral DMTs
People with multiple sclerosis (MS) who receive anti-CD20 therapies such as Ocrevus (ocrelizumab) are significantly less likely to discontinue their treatment compared with patients who are given other disease-modifying therapies (DMTs), a Swiss study has found.
Staying on treatment may be related to the effectiveness of B-cell-depleting therapies at reducing the rate of relapses, especially when compared with oral DMTs. Lack of efficacy was among the most cited reasons for people on oral DMTs to discontinue their treatment.
“MS patients were more persistent to BCDT [B-cell-depleting therapies] than to other DMT. The longer persistence on BCDT as compared to oral DMT might be explained by a higher effectiveness in reducing inflammatory disease activity,” researchers wrote.
The study, “Treatment persistence and clinical outcomes in patients starting B cell depleting therapies within the Swiss MS Cohort,” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical. It was funded by Roche, the parent company of Genentech, which markets Ocrevus.
More than 20 DMTs approved for MS
More than 20 DMTs are approved for MS and are designed to alter the course of the disease. These medications primarily work by reducing inflammation in the brain and spinal cord, which is a key driver of the cell nerve damage seen in MS. By suppressing inflammation, DMTs can help reduce disease activity, seen in the form of relapses and lesions, and slow down the progression of disability associated with MS.
While all have been proven effective in MS, some medications are generally better at reducing disease activity and the progression of disability than others. They also have greater safety issues and are usually associated with more severe side effects.
B-cell-depleting therapies such as Ocrevus and rituximab are medications that fall under the category of highly-effective therapies. They work by targeting a protein called CD20 at the surface of B-cells, which are key drivers of inflammation in MS, causing their death.
However, little is known about the relationship between treatment efficacy and the likelihood of patients remaining on their prescribed treatment regimen.
To address this gap, researchers in Switzerland examined data from 853 people with relapsing-remitting MS (RRMS) included in the Swiss MS Cohort who started on a new DMT after November 2013.
Of them, 269 started the CD20 inhibitors Ocrevus or rituximab, which is used off-label for MS. The remaining received platform therapies (57 patients) such as interferon-based medications or glatiramer acetate (sold as Copaxone, among others), oral DMTs (454 patients) such as Gilenya (fingolimod), Aubagio (teroflunomide), and Tecfidera (dimethyl fumarate). A group of 73 patients received Tysabri (natalizumab).
Tysabri is another DMT considered highly effective. Platform therapies are those that are less effective but were used as first-line treatment before more effective therapies were approved, and oral therapies are generally considered moderately effective.
Results showed patients who started on anti-CD20 medications had a 75% lower risk of discontinuing their therapies compared to those on other DMTs, indicating they had a higher chance of sticking to their prescribed treatment.
Continuing with B-cell-depleting therapies remained consistently higher
When other DMT groups were compared separately, continuing on B-cell-depleting therapies remained consistently higher, with patients on those therapies having a 72% lower risk of discontinuing compared with those on oral DMTs, and a 65% lower risk of discontinuing compared with patients on Tysabri.
When looking at treatment effectiveness, CD20 inhibitors were associated with a 48% lower risk of relapses, reflecting reduced inflammatory activity. The difference was also significant when B-cell-depleting therapies were compared with oral DMTs, but no significant differences in relapse rates were observed between patients on CD20 inhibitors and Tysabri.
No significant differences in six-month confirmed disability worsening (CDW), defined as an increase in Expanded Disability Status Scale (EDSS) scores lasting at least six months, were observed between groups. However, there was a trend toward a lower risk of CDW with anti-CD20 therapies compared to oral DMTs, with differences becoming evident after about four years of treatment. The researchers noted the full impact of therapies on disability progression may take longer to show than their impact on relapses.
The study also explored the relationship between relapses and treatment discontinuation. Patients taking oral DMTs were more likely to experience relapses while on the medication (28.7%), followed by Tysabri users (14.7%), compared to 7.7% of those on B-cell therapies.
Consistently, the main reason for discontinuing treatment among those on oral DMTs was lack of efficacy (30.3%), followed by side effects (25.9%). For those on Tysabri, about one-third of discontinuations were due to safety concerns related to progressive multifocal leukoencephalopathy, a life-threatening brain infection that can develop with prolonged Tysabri treatment.
In contrast, no patient who discontinued CD20 inhibitors cited a lack of efficacy as the reason for stopping, and 2.6% said they discontinued due to side effects or lack of tolerance.
These findings suggest B-cell therapies may better control disease activity while maintaining a favorable safety profile, contributing to the higher adherence rates compared to other therapies. However, longer follow-up is needed to observe their impact on disability progression over time.
“We highlight the need of pragmatic randomized trials comparing different DMT including BCDT in terms of both efficacy and safety outcomes in the long term,” the researchers wrote.
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