Early Disease Activity in MS Seen to Have Little Long-Term, Prognostic Value

A large study of multiple sclerosis patients (MS) came to the conclusion that clinical and brain imaging assessments drawn from magnetic resonance imaging (MRI) scans are poor measures of long-term prognosis for patients.

The study, “Long-term evolution of multiple sclerosis disability in the treatment era,” published in the journal Annals of Neurology, also showed that a lack of disease activity in the immediate years following disease onset does not predict later outcomes, and questions the use of yearly MRI assessments and whether aggressive early treatment to halt disease activity can actually ensure lower disability over time.

Researchers at the University of California San Francisco followed 517 MS patients over time. The vast majority (91%) were followed for up to 1o years. The team wanted to determine if brain scans and clinical assessments could be used to set a prognosis of disability development.

Results showed that in patients with relapsing MS, disability level at study start, as measured by the Extended Disability Status Scale (EDSS), did not impact how the disease progressed over the following decade, and only 55.3% had a worse disability score at the study’s end. For patients with progressive MS forms, worsening occurred in 75% of the patients. Those with EDSS scores lower than 3 at study start all worsened during the 10-year period.

Women had a slightly smaller risk of transitioning from relapsing to secondary progressive MS, while people who had become ill later in life had a higher risk.

Most relapsing MS patients, 82%, experienced disease activity during the first two years, either in the form of symptoms or brain lesions, with only 73 patients being NEDA (having no evidence of disease activity). NEDA is defined as a total absence of relapses, of increased disability lasting more than three months, and of the presence of MS lesions. The total lack of disease activity during the first two years could not be used to set a prognosis of how the disease had evolved at year 10.

The team also measured if disease activity assessed through imaging during a two-year period could predict disability development during a 10-year period, but found no links. This was also true for patients who did not have any symptoms, while having new brain lesions identified by scans.

Surprisingly, patients whose disability scores worsened during the first two years had a lower risk of worsening in the following years. Only in relapsing patients who later developed secondary progressive MS was an initial worsening in scores linked to subsequent decline — but as this can only be confirmed once a patient’s disease progresses, the data cannot be used for setting a prognosis.

While lower vitamin D levels during the first two years were linked to more short-term disease activity, early levels could not predict long-term development.

Long-term outcomes also did not differ between patients who, at some time point during the first two years, intensified their treatment compared to those who did not.

Two years ago, a study came to the opposite conclusion, showing that NEDA was a good predictor of later disease progression. The study suggested that NEDA should be the goal of MS treatment, which should follow a treat-to-target approach — a concept adapted from the treatment of rheumatoid arthritis, where more aggressive treatments are used sooner to reach the goal of no disease activity.

These new findings questioned whether yearly brain scan evaluations are a good way to define the necessary steps in such an approach.

Several authors contributing to the study have financial interests in pharmaceutical companies producing MS disease modifying drugs.