Combination Therapy Provides Similar Clinical Benefit as Single Drug Treatment in People with MS
Drugs taken together do not reduce risk of relapse but appear to prevent development of new lesions
People with multiple sclerosis (MS) who were treated with combination therapy did not see significant clinical benefit over those treated with single drug therapy, but combination therapy did reduce the development of new lesions, according to an international research team led by The Mount Sinai Medical Center. The findings, part of the largest-ever MS trial sponsored by the National Institutes of Health, are published in the March 11 issue of Annals of Neurology.
In the Phase III CombiRx trial, researchers led by Fred Lublin, MD, of The Mount Sinai Medical Center, sought to determine if Glatiramer Acetate (GA) and Interferon Beta-1a (IFN), the two most commonly-prescribed drugs for relapsing-remitting MS (RRMS), were more effective in combination than as monotherapies. The results showed that while combination therapy was no better than monotherapy, patients who took combination therapy had a reduction in new lesions on MRI scan.
“This is the first NIH-sponsored, multi-center, comparative trial evaluating the benefits of both combination therapy and monotherapy in MS,” said lead author Fred Lublin, MD, Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at The Mount Sinai Medical Center. “The study is the first to show that a combination trial is feasible in MS, to compare a combination to established monotherapy, and to provide comparative efficacy data for two commonly-prescribed drugs.”
The research team enrolled 1,008 participants from 68 sites to receive IFN plus GA (499), IFN alone (250), or GA alone (259), with 30µg IFN administered intramuscularly weekly and/or 20 mg of GA injected daily. The groups were followed for three years to assess if the combination therapy reduced MS relapse rates.
While combining IFN and GA was safe and effective, patients taking this regimen did not see clinical benefit greater than those taking a single agent. There was no substantial improvement in neurological function in participants in the combination therapy group. They also found that GA alone was superior to IFN alone in reducing relapse rates. MRI findings also suggested that the IFN plus GA together were better in reducing new lesions and total lesion accumulation than either drug alone.
“While there was no substantial clinical benefit of combination therapy over monotherapy, we will continue to monitor these patients to see if the reduction in MRI lesion translates into a future clinical benefit,” said Dr. Lublin. “The CombiRx study also provides a large dataset to analyze different aspects of the disease, such as potential biomarkers for prognosis and response to therapy.”
The National Institute of Neurological Disorders and Stroke (NINDS) provided funding for the CombiRx clinical trial (grant #UO1NS045719 and R21NS41986), which will continue to evaluate the cohort for four more years.
“The investigators were successful in implementing a clinical trial comparing the effectiveness of a two-drug combination to treatment with a single drug,” said Petra Kaufmann, MD, MSc, Associate Director for Clinical Research, NINDS. “The trial answered an important question to the MS community: The results did not show a clinical benefit in people taking two drugs rather than one drug. In addition to answering this question, the trial has resulted in valuable clinical and imaging observations that can help researchers to better understand the course of MS and that can inform the planning of future trials.”
The NINDS describes MS as a neuroinflammatory disease, which affects the central nervous system by attacking myelin, a substance found in nerve fibers, and causing lesions. NINDS estimates that up to 350,000 individuals in the U.S. have MS, which affects twice as many women as men, with most symptoms appearing between the ages of 20 and 40. Experts believe this complex autoimmune disease may be caused by genetic and environmental factors.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine at Mount Sinai is one of the leading medical schools in the United States. The Icahn School of Medicine is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty members in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of just 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.