Multiple sclerosis (MS) that appears to be “genuinely benign” 15 years after diagnosis is evident in a small number of patients, a large population-based study from the U.K. reports.
But, its researchers note, the term “benign” is often not clinically accurate as used, because it is based largely on perceptions of disease impact.
The concept of benign MS is controversial, especially among clinicians. Still, long-term epidemiological studies have consistently identified a small fraction of patients whose MS progresses very slowly over a long span of years.
Determining the prevalence of this type of MS in the population has been difficult, as estimates can vary significantly depending of the definition of “benign” that is adopted.
Researchers sought to determine an accurate estimate of benign MS in the U.K. population, using a rigorous and comprehensive clinical definition of a truly benign disease.
This definition included minimal physical disability (EDSS score of less than 3), and no significant fatigue, mood disturbance, cognitive impairment or interrupted employment in the absence of treatment with disease-modifying therapies over 15 years or more years after symptom onset.
They screened an U.K. population-based registry containing data on 3,062 MS patients to identify those with “unlimited walking ability” 15 or more years after diagnosis.
A representative sample of 60 patients from this pool was analyzed (45 women and 15 men, mean age of 57); they had a mean disease duration of 28 years.
Nine out of these 60 (15%; 8 women and one men) fulfilled the study’s criteria for truly benign disease. These nine people had a mean age of 27 at symptom onset, a median EDSS disability score of 1.5 (minimal signs of disability), and a mean disease duration of 31 years.
“Those nine individuals with truly benign MS all remained in a relapsing–remitting state,” the study noted. “However, only two out of nine showed disease arrest within the first decade; the remainder all continued to experience relapses well into their second or third decade of MS,” but the rates of such relapses were low.
MS in the remaining patients was not classified as benign, mostly due to evidence of cognitive difficulties (57%), and the disease’s impact on employment status (52%) with many taking early retirement.
Based on these results, a population frequency for “benign MS” under the definitions used was estimated at 2.9%.
But the researchers noted that a large proportion of patients (65%; 39 patients out of 60) reported their disease as benign, according to a lay definition. Their self-reported status poorly agreed with the clinical assessments done throughout the study.
“There is no accepted definition to offer patients when exploring whether they feel their MS is benign; the definition we chose incorporates the fundamental principles of low impact on a person, absence of complications and a favourable outcome and is in line with definitions provided by third-party support groups,” the researchers wrote.
Many considering themselves with benign disease did so based on their “perception” of their disease, the team added, and one that “appeared to be driven as much by mood, fatigue and bladder function as by physical ability.”
“In conclusion, after detailed clinical assessment, a small minority of people with MS appear genuinely unaffected by symptoms after 15 years,” the researchers added.
They also called attention to the fact that EDSS-based definitions of benign MS and the inconsistency between patient and clinician perception of benign MS compromise the use of the term ‘benign’ in clinical practice.
They also emphasize that studying individuals with benign MS “has the potential to uncover clues to mechanisms underlying favorable outcomes in MS, provide insights into new therapeutic targets and have implications for patient counselling, individual patient management and the construct of clinical trials.”