Research News

Cleveland Clinic has received $6.7 million from the Patient-Centered Outcomes Research Institute (PCORI) to follow patients with multiple sclerosis over nine years after an initial clinical trial to assess treatment approach and impact on outcomes and quality of life. Led by neurologist Daniel Ontaneda, MD, PhD of Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research, the follow-up study aims to assess long-term effects of starting with powerful, highly effective MS treatments versus beginning with safer, less aggressive options and escalating as needed

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the brain and spinal cord and is a leading cause of disability among young adults, particularly in North America and Europe. There are currently two main strategies for treating MS. The first is called the "escalation" approach, which involves starting with a treatment that is generally safer but may not be the best at controlling MS activity. If the disease continues to worsen, clinicians will then switch to more powerful treatments. The second approach is known as "early highly effective treatment” and uses a more powerful treatment from the start, which can be highly effective but may come with a risk of more complications. The treatment can increase the risk of severe infections because of its immunosuppressive properties. There is no agreed-upon methodology for deciding which approach to take, Dr. Ontaneda says.

“Having over two dozen approved MS treatment options is a huge advantage for doctors and patients, but there’s not a lot of clarity or data on the best types of medication or treatment plan to implement at the outset of the disease,” Dr. Ontaneda says. “With PCORI’s generous support, we’ll be able to finally provide concrete data to help guide physicians to determine the most effective and safe option for their patients.”

PCORI funded the initial study in 2017 with a grant for $10.6 million, which compared the two approaches in 400 participants. In the first phase of the trial, researchers examined whether brain volume loss on MRI over three years was greater in the early highly effective or escalation groups. As the initial 3-year phase of the study ends, Dr. Ontaneda and his team are shifting their focus to the next stage in a study called “Comparing the long-term effectiveness of initial treatment approaches for relapsing-remitting multiple sclerosis on the prevention of disability” which will instead focus on the patients’ clinical outcomes. The new phase will continue following the same participants from the first study for up to nine years from when they initially enrolled, looking for any changes in tests that indicate changes in disability. The study will also track clinical measures and the safety and tolerability of the treatments, including serious adverse effects. Investigators plan to gather participants' perspectives on their symptoms and quality of life to examine how the treatment approaches affect mental health and overall well-being. 

Because this study examines treatment philosophies, and not just specific medications, Dr. Ontaneda says the results can also guide the use of any new MS treatments that come to market.

“We designed this study to be pragmatic and replicate clinical practice as much as possible by instituting a wide inclusion criterion, and we recruited patients not just from academic sites, but also community-based sites,” Dr. Ontaneda explains. “The results of this study will give the power of information to clinicians and their patients and help guide their overall philosophy of treatment in a way that has not been possible before.”

Cleveland Clinic is part of PCORI’s Health Systems Implementation Initiative (HSII), which connects selected health systems across the U.S. to reduce the time needed to bring a research discovery to patient care. Cleveland Clinic launched its own Healthcare Delivery & Implementation Science Center in 2019, initiated by Tom Mihaljevic, MD, CEO, President and Morton L. Mandel CEO Chair of Cleveland Clinic. Beri Ridgeway, MD, Cleveland Clinic’s Chief of Staff is co-lead on programs through the Health Systems Implementation Initiative. PCORI also supported a new hypertension program, which implements a proactive approach to reach more patients and better treat high blood pressure.

“We know as physicians that these early treatment decisions can shape a patient’s quality of life for years to come,” Dr. Ridgeway says. “This project is a wonderful example of what we can do as part of the HSII – providing valuable information to benefit care all over the world based not just on what we see immediately, but on what patients say years after their initial treatment. It is essential feedback to make sure we’re providing patients the most support we can.”