Better Therapies, Management of Comorbidities Improving Long-term Outcomes in MS, Speakers Say

Improvements in disease-modifying therapies (DMTs), along with lifestyle changes and better disease management, are delivering better health and quality of life for those diagnosed with multiple sclerosis (MS), said experts who spoke at the session, “What determines the long-term outcome of MS?” held September 11 at ECTRIMS 2019, the 35th Annual Congress of the European Committee for Treatment and Research in Multiple Sclerosis, taking place in Stockholm, Sweden.

Ali Manouchehrinia, PhD, of Karolinska University Hospital, Stockholm, said that the use of data has allowed researchers to evaluate the clinical course of MS, and to make better use of imaging and biomarkers to understand the disease, including the long-term effects of relapse.

Researchers are gaining an appreciation that the “correlation of EDSS and cognitive impairment is at best moderate,” Manouchehrinia said, referring to the Expanded Disability Status Scale, which grades patients from 0 to 10 based on physical functioning, with 6 being the point at which patients cannot walk without a cane.

But there’s also an acknowledgement that much of the understanding of MS comes from the patients who show up at clinics, and this group may include patients who are more impaired. One thing that’s becoming clear, Manouchehrinia said, is that the span of time between an MS diagnosis and severe disability is becoming longer, with much heterogeneity even within countries.

In a review of clinics in Sweden, for example, half as many patients are reaching an EDSS score of 6 by age 64 as once did. “In the heavily treated MS population, disability appears to evolve more slowly,” he said.

This change is coming alongside savings to health and disability systems, Manouchehrinia said. In both developed and developing countries, he added, the cost of illness is dropping overall. In Sweden, “while the costs of treatments are going up, the cost of MS disability pension, sick leave, and absences are going down.”

This is due to patients living with milder disease—which Manouchehrinia said is due in part to the use of the DMTs starting in mid-1990s. However, that’s not the whole story.

More effort is made to diagnose MS early, so fewer patients are being diagnosed with progressive MS, he said. Instead, more patients today are managed with relapsing-remitting MS. Besides better therapies, “Lifestyle could be a reason. Smoking is a big risk factor,” in MS, and, “We have seen a global trend in a decreased rate of smoking, especially among women.”

Finally, “The other reason is the improvement in management of symptoms. Fatigue, depression, [and] cognitive function are now being taken seriously—we tackle these problems proactively,” Manouchehrinia said. Comorbidities are managed and studied in MS using population-level data, and international efforts are underway to share data so that researchers can understand the factors that affect disease progression within subgroups.

“It looks like the clinical course of MS is changing,” he said.

Ruth Ann Marrie, MD, PhD, professor of medicine and community health at the University of Manitoba, Canada, delved further into the need to understand how comorbidities affect the course of MS, starting with how they can affect or delay the initial diagnosis.

The common wisdom is that disability in MS increases with age, but it’s not that simple. “There’s still a vast amount of heterogeneity in MS that is not explained by those factors,” Marrie said. “There are things about the underlying biology … we are beginning to fill those in.”

Data from 23,000 Canadians is helping shed light on the role of comorbidities. The lowest burden occurs among the youngest MS patients, and the burden rises as people age. “Over the course of the disease,” she said, “the burden is going to rise; depression and anxiety remain common,” and this can affect which phenotype of MS a patient develops.

Having more comorbidities also increases the relapse rate, and some comorbidities are more problematic than others. Reviews of medical records suggest that hyperlipidemia and migraine are linked to relapse; depression is linked to secondary progressive phenotype.

Other research shows a link between having multiple comorbidities and reduced walking speed, and this seems especially true for people with MS alongside diabetes or hypertension. (A separate study presented earlier in the day found that diabetes was linked to elevated levels of serum neurofilament light chain, a biomarker in MS.¹)

High levels of low-density lipoprotein cholesterol and triglycerides are also linked to greater EDSS scores, Marrie said.

“A constellation of comorbidities contributes to worse outcomes,” she said.

Depression and anxiety are especially challenging in MS, because not only do they both harm quality of life, but they may also affect treatment, and it’s not always clear if they are present in dependent of MS, or if they appear as a result of the diagnosis.

The important takeaway, Marrie said: addressing comorbidities up front is essential to successful treatment of MS. “Given that comorbidity has such a pervasive effect, could we exert pervasive effect by addressing it from the beginning?"

Reference

1. Fitzgerald K, Sotichros E, Smith M, et al. Serum neurofilament light chain is associated with MS outcomes and comorbidity in a large population of people with multiple sclerosis. Presented at 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis; Stockholm, Sweden; September 11-13, 2019. Abstract 23.