Originally designed as a three-year study to address the controversy of whether it’s better to escalate disease-modifying therapy for multiple sclerosis (MS) or treat with highly effective medications from the start, the multicenter DELIVER-MS trial is being extended. With $1.1 million in funding from the National Multiple Sclerosis Society, the DELIVER-MS LTE extension will generate data on participants for an additional three years with a focus on clinical endpoints.
Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services Policy
“The primary outcome of the original study is brain loss from baseline to 36-month follow-up,” says Cleveland Clinic neurologist Daniel Ontaneda, MD, PhD, who serves as co-principal investigator along with Emma Tallantyre, BMBS, PhD, of the University of Cardiff. “We believe it will be even more meaningful to look at disability outcomes over the long term. The new award will enable us to focus on clinical outcomes rather than just imaging results.”
The study in brief
DELIVER-MS LTE is an extension of DELIVER-MS, which was funded by the Patient-Centered Outcomes Research Institute and is one of only two prospective clinical trials directly comparing two disease-modifying therapy (DMT) strategies:
- Escalation, which involves starting with a medication that’s considered safe but not highly likely to control the patient’s MS activity, and then escalating to progressively more-potent therapies if disease activity is not controlled.
- Early highly effective treatment (EHT), which involves first-line use of a medication with high rates of efficacy but also the potential for rare significant adverse effects. The term EHT is reserved for the most efficacious agents, all of which are monoclonal antibodies (alemtuzumab, natalizumab, ocrelizumab, ofatumumab, rituximab and ublituximab).
To date, more than 700 people with MS are participating in DELIVER-MS. Target enrollment is 400 adults with relapsing-remitting MS in the randomized clinical trial across 15 sites in the U.S. and 16 in the United Kingdom. Another 400 adults with relapsing-remitting MS who are unsuitable for randomization or prefer a particular DMT are being enrolled in a parallel observational cohort.
The new funding expands follow-up in DELIVER-MS from three to six years, ending in January 2026. Approximately 132 study participants will reach the 72-month visit (Year 6), 310 will reach the 60-month visit (Year 5) and 498 will reach the 48-month visit (Year 4) with the current funding. The extension also supports further use and validation of candidate biomarkers and their association with long-term treatment response and disease. The researchers hope the data generated can be used to shape personalized medicine approaches to MS.
Investigators in DELIVER-MS and DELIVER-MS LTE are assessing the impact of escalation and EHT by using MRI to measure changes in brain volume. Brain atrophy is a surrogate marker predictive of long-term disability in MS.
A deeper take on disability
The key objective of DELIVER-MS LTE is collection and analysis of long-term disability data from participants to detect disability progression, defined based on worsening on the 10-point Expanded Disability Status Scale and measures from the Multiple Sclerosis Functional Composite. Patient-reported outcomes on the MSIS-29 and Neuro-QoL instruments are being used to measure quality of life as related to neurological disease.
The investigators also expect new insights into whether disability is accumulated as relapse-associated worsening or progression of independent relapses (PIRA). Examining the presence of PIRA is particularly important because with escalation therapy, PIRA may go relatively unnoticed, which could prove to be a major differentiator between escalation and EHT.
“Until recently, we believed that individuals with relapsing-remitting MS accumulate disability when relapse recovery is incomplete, and we hoped that disability could be prevented if EHT completely abrogated relapse,” Dr. Ontaneda says. “Evidence has shown that’s not the case. We don’t know why some patients have PIRA. With this study, we’ll be comparing subsets of patients in the EHT and escalation groups who don’t have relapses to see if they’re accumulating disability in different ways that we can target for treatment.”
Other outcomes of interest
Long-term collection of patient-reported outcomes and data on adverse events in DELIVER-MS LTE will crucially allow the researchers to assess whether any efficacy gains from MS therapy are offset by excess risks or a reduction in quality of life or treatment satisfaction. Although current funding is for six years, the ultimate goal is to follow participants up to 10 years from initial enrollment, according to Dr. Ontaneda.
“COVID-19 hit in the middle of DELIVER-MS, delaying enrollment, but we’re already seeing some interesting pre- and post-pandemic medication patterns,” he says. “For example, use of B-cell-depleting therapy appears to have increased during the pandemic, but we expected a decline because of its association with higher risk of COVID complications.”
A report on baseline data from DELIVER-MS is anticipated in the fall, via an abstract at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress. “The parallel observational cohort is being followed the same as the randomized arms,” Dr. Ontaneda notes. “In that cohort, we’ll be looking at predictors of willingness to be randomized and choice of EHT versus escalation therapy. One of our real-world observations so far is that escalation therapy seems to be favored more in the U.K. than in the US.”