ACTRIMS 2023: Ibudilast did not lift life quality in progressive MS trial

Treatment with the experimental oral therapy ibudilast (MN-166) does not significantly improve quality-of-life measures compared with a placebo among people with progressive forms of multiple sclerosis (MS), according to new data from a Phase 2 clinical trial.

Analyses from the trial suggest that a marker of nerve damage called neurofilament light chain, or NfL, may be useful for predicting mental well-being among progressive MS patients.

These data were presented in a poster, “Assessment of Ibudilast Treatment Effect and Predictive Utility of Serum Neurofilament Light Chain Levels on Quality-of-Life Scores in the SPRINT-MS Clinical Trial,” at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023, which took place Feb. 23-25 in San Diego. The work was funded by the U.S. Department of Defense.

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The therapy was tested in a Phase 2b trial, called SPRINT-MS (NCT01982942), which enrolled 255 people with progressive types of MS — 134 with primary progressive MS (PPMS) and 121 with secondary progressive disease (SPMS).

Participants were randomly assigned to take ibudilast or a placebo for 96 weeks, or about two years. During the trial, patients could continue receiving their glatiramer acetate (sold as Copaxone and generics) or interferon-beta therapies, or were given no other disease-modifying treatment.

The trial met its main goal of showing that ibudilast significantly slowed the rate of atrophy (shrinkage) in the brain. The treatment also protected nerve cells in the retina, the region of the eye that houses light-sensing cells.

We found that ibudilast did not really affect quality-of-life scores, although we know that it slowed rates of atrophy in the brain and in the retina.

During the SPRINT-MS trial, participants’ quality of life was regularly assessed with a standardized test called the short form 36 health survey (SF-36).

In the ACTRIMS poster, researchers used data from this survey to derive two scores: a physical composite summary (PCS) reflecting physical health, and a mental composite summary (MCS) indicative of mental well-being. The team then assessed the effect of ibudilast treatment on these scores.

“We wanted to know the effect of ibudilast on the quality-of-life scores, in terms of the physical health outcomes and the mental health outcomes,” said Hussein Moussa, MD, a postdoctoral researcher at Johns Hopkins University who presented the findings at ACTRIMS.

Results showed that, over the course of the 96-week trial, the rate of change for both PCS and MCS was not significantly different between patients given ibudilast or a placebo. Analyses of the SPMS and PPMS patients separately also did not show a significant effect of ibudilast on life quality measures.

“We found that ibudilast did not really affect quality-of-life scores, although we know that it slowed rates of atrophy in the brain and in the retina,” Moussa said.

Hussein Moussa, MD, postdoctoral research fellow at Johns Hopkins University. Photo taken at the ACTRIMS Forum 2023.

The team noted that other analyses from the trial also showed no difference between the ibudilast and placebo groups in terms of disability progression, as measured by the Expanded Disability Status Scale (EDSS). These data collectively suggest that “measurable brain and retinal atrophy benefits may not necessarily translate into measurable clinical benefits” for people with progressive MS, the researchers wrote.

Moussa noted that another possible explanation for these findings could be that the instruments used to measure the clinical effect might not be sensitive enough to detect a meaningful change — both SF-36 and EDSS are fairly general measures.

Other more specific and sensitive measures, such as assessments of the brain’s processing speed, “might be more helpful in measuring clinical outcomes and how the disease progresses over time,” Moussa said.

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Higher baseline NfL levels linked to worse mental well-being in PPMS

In other analyses, the researchers assessed life quality outcomes based on levels of NfL, a well-established biomarker of nerve damage.

Results showed that patients with higher starting (baseline) NfL levels — specifically above the 97.5 percentile of normal values — tended to have a faster decline in MCS scores, by 24.3%. The association between higher baseline NfL levels and worse mental well-being was particularly prominent among the PPMS patients, but was not statistically significant for SPMS patients.

“Baseline NfL levels [in blood] may predict a decline in MCS scores in people with [progressive] MS, more prominently in the PPMS subtype,” the researchers concluded.

Moussa said the association between mental scores and NfL was unsurprising given that NfL is a marker of nerve damage, and damage to nerves in the brain is known to lead to issues with cognition. However, the fact that the association was found in PPMS but not SPMS was unexpected.

“This finding may emphasize the fact that PPMS and SPMS have two distinct disease development” patterns and underlying mechanisms, Moussa said, though he stressed that additional studies are needed to validate the results.

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ACTRIMS Forum 2023 Feb. 23–25. Go here to see the latest stories from the conference. Follow along on Facebook, Twitter, and Instagram for live updates using the hashtag #actrims2023.