Ublituximab Shows Sustained MS Benefit Over 5 Years in Extension Study

New data presented offer encouraging long-term insights into the efficacy and safety of ublituximab, an emerging treatment for relapsing forms of multiple sclerosis (MS). An interim analysis of an ongoing open-label extension study suggests sustained reductions in relapse rates and disability progression among individuals treated with the medication, even extending to five years of use. The findings, published in JAMA Neurology, add to a growing body of evidence supporting ublituximab’s potential as a valuable therapeutic option for people living with MS.

Long-Term Efficacy and Safety Profile

The study, led by Bruce A. C. Cree, MD, PhD, MAS, of the University of California, San Francisco, analyzed data from 851 adults with relapsing MS. Participants either continued to receive ublituximab or switched from teriflunomide to ublituximab. Researchers assessed annualized relapse rates, 24-week confirmed disability progression, and 24-week confirmed disability improvement over the extended treatment period.

Notably, the annualized relapse rate continued to decrease with up to five years of ublituximab treatment. For those who continued ublituximab, the rate fell from 0.053 at year 3 to 0.02 at year 5. Individuals who switched to ublituximab from teriflunomide also experienced a significant drop in relapse rates, decreasing by 58.4% at year 3 and remaining low through year 5.

the study demonstrated a notable impact on disability progression. At year 5, 92% of adults receiving ublituximab were free of 24-week confirmed disability progression. The risk of confirmed disability progression was significantly reduced in the group that continued ublituximab compared to those who switched from teriflunomide (HR = 0.61; 95% CI, 0.41-0.9).

“This study shows two very important features that clinicians need to understand about ublituximab use,” Dr. Cree told Healio. “The first is that ublituximab treatment has robust impacts on prevention of MS disability both in terms of confirmed disability worsening and confirmed disability improvement.”

Understanding Ublituximab and its Mechanism

Ublituximab is a monoclonal antibody that selectively targets CD20-positive B cells. B cells play a role in the immune response that drives the inflammation and demyelination characteristic of MS. By depleting these B cells, ublituximab aims to reduce the autoimmune attack on the central nervous system. Real-world data has demonstrated similar clinical benefits to those observed in phase 3 studies.

Safety Considerations

The study also addressed the long-term safety profile of ublituximab. Researchers reported relatively stable immunoglobulin M and G levels, generally remaining above the lower limit of normal. Importantly, serious infection rates did not significantly differ between individuals with normal immunoglobulin levels and those with lower levels, suggesting that hypogammaglobulinemia—a potential side effect of B cell depletion therapies—did not substantially increase infection risk in this cohort.

Serious infection rates were 2.1 per 100 participant-years in the continued ublituximab group, and 2.58 per 100 participant-years in the switched group. These findings align with the established safety profile observed in pivotal trials.

Implications for MS Treatment Strategies

The findings from this long-term extension study have important implications for how clinicians approach MS treatment. Dr. Cree emphasized that ublituximab treatment is generally safe and well-tolerated over five years, with low rates of hypogammaglobulinemia and no clear association between infection and low immunoglobulin levels.

“The second is that ublituximab treatment is generally safe and well tolerated over 5 years with very low rates of hypogammaglobulinemia and no clear associations of infection with hypogammaglobulinemia,” Dr. Cree said. “Ongoing, even longer-term studies will help address potential risks and benefits beyond 5 years.”

The data also suggest that initiating treatment with ublituximab may be superior to a “treat-to-target” approach, where treatment is escalated based on disease activity. The diverging survival curves for disability progression between the two groups with longer follow-up support this idea. This observation aligns with ongoing research, including the TREAT-MS and DELIVER-MS trials, which are investigating the optimal treatment strategies for MS.

Future Research Directions

While the current study provides valuable insights, further research is needed to fully understand the long-term effects of ublituximab. Future studies will focus on assessing the safety and efficacy of treatment beyond five years, as well as investigating the potential impact of hypogammaglobulinemia on infection risk and the need for immunoglobulin supplementation. The full study was published in JAMA Neurology.

As Dr. Cree noted, “These and long-term studies of other anti-CD20 products underscore the profound clinical impact of this treatment class on relapsing MS biology that has important clinical considerations for patients living with MS.”

For more information:

Bruce A. C. Cree, MD, PhD, MAS, can be reached at [email protected].