Disease-modifying therapies may delay disability progression in patients with primary progressive multiple sclerosis (PPMS) if they are treated early in the course of their disease, according to data presented during MS Virtual 2020, the joint meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis.
The earlier individuals were started on disease-modifying treatment, the longer it took for their disability to progress to the point where they had to use a wheelchair—reflected in a score of 7 on the Expanded Disability Status Scale (EDSS), study author Massimo Filippi, MD, professor of neurology at Vita-Salute San Raffaele University, and chair of neurology at the MS Center and Neuroimaging Research Unit at San Raffaele Hospital in Milan, Italy, told Neurology Today At the Meetings.
Moreover, treating younger patients and reducing the delay to treatment initiation may improve the patients' long-term disability outcomes, he said. To optimize treatment decision-making in PPMS, further profiling of the best candidates for treatment is needed.
"Our findings suggest that these patients could benefit from an early treatment start that could reduce, at least partially, the accumulation of clinical disability," Dr. Filippi said. "This could have relevant implications in the management of PPMS patients."
Using the Italian MS Registry, the researchers identified 1,214 patients with PPMS who had at least three EDSS evaluations and three-years of follow-up; 790 (65 percent) of the group received a disease-modifying treatment. The first EDSS evaluation was considered the baseline for that person in the study for untreated patients, and the date of the first disease-modifying therapy as initiation for treated patients.
After a mean follow-up of 11.6 years, 994 individuals, or 82 percent of the entire sample, had an EDSS score of 6, that is, they required intermittent or unilateral constant assistance with a cane, crutch, or brace to walk about 100 meters with or without resting; 539 patients (44 percent) reached an EDSS score of 7, meaning they were unable to walk beyond approximately five meters even with aid and were essentially restricted to a wheelchair.
When the patients were stratified by those who received treatment and those who did not receive disease-modifying therapy, there was no statistically significant difference in the time to decline where wheelchair use was required.
Patients in the top quartile of use of disease-modifying agents had a 27 percent decreased risk of reaching an EDSS of 7, however, when compared with patients in the lowest quartile of use, Dr. Filippi reported.
The researchers noted that the average time from MS diagnosis to use of disease-modifying therapy was about 6.8 years. And the individuals treated the longest and in the top tier of disease-modifying drug use were generally younger, with an average age of 44.1 years at the time they first received the drugs.
"This new treatment paradigm is rewarding for several reasons," Dr. Filippi said. "Results from different randomized controlled trials and observational studies in progressive MS have consistently shown that specific disease-modifying drugs are more effective in patients who are younger and have a shorter disease duration."
"This is not surprising, because these patients typically present a higher inflammatory activity that is the main target of the different MS treatments currently available," he explained. "Conversely, in patients who are older, have a longer disease duration, and show a more severe disability, the beneficial effects of MS treatments are more limited. Accordingly, in these latter patients, the balance between treatment benefits and risk is less favorable."
Commenting on the study, Stephen Krieger, MD, FAAN, associate professor of neurology at the Icahn School of Medicine at Mount Sinai in New York City, said: "This large real-world study is worthwhile because we really can't do these long-term studies in clinical trials."
"It is disappointing they didn't find a difference between taking medication or not, but there may be a lot of reasons for that," Dr. Krieger said. "It could be that the patients treated with disease-modifying therapy were progressing more rapidly. It is hard to control for that even in a propensity score analysis. It is hard to adjust for all things."
Dr. Krieger noted that the researchers did find that earlier treatment among those who received treatment did show a delay to the need for use of a wheelchair. "That makes sense," he said, "because it often takes longer for a drug to exert its therapeutic effect."
He said that because most of the patients were using drugs designed to help people with relapsing-remitting multiple sclerosis rather than treatment for progressive disease—and some patients had a benefit from the treatment—it supports a theory that the distinction between relapsing-remitting disease and progressive disease is somewhat blurred.
"There is a lot of overlap between what we conceive of as relapsing disease and primary progressive multiple sclerosis. These data sort that notion," Krieger said.
Dr. Filippi disclosed relationships with Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Krieger disclosed relationships with Biogen, EMD Sorono, Genentech, Genzyme, Mallinckrodt, MedDay, Novartis, Teva, and TG Therapeutics.
Link Up for Related Information:
MS Virtual 2020 Abstract PS05.04: Fonderico M, Portaccio E, Iaffaldano, et al. Disease modifying treatment may delay time to wheelchair in primary progressive multiple sclerosis: A real-life cohort.
Lorscheider J, Kuhle J, Izquierdo G, et al, for the MSBase Study Group. Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: A cohort study. Eur J Neurol 2019;26(2):363-370.