Study Links Early Progression Independent of Relapse Activity to Worse Long-term Disability in Patients with MS

Multiple sclerosis (MS) is categorized into four types based on the frequency of symptoms and the course of the disease progression.

Relapsing-remitting MS (RRMS) is the most common form of MS. Patients with RRMS typically experience episodes of new or worsening symptoms (relapse) followed by symptom-free periods. Eventually, RRMS changes into secondary-progressive MS (SPMS), in which patients experience a steady decline in disability and worsening of symptoms.

The less common forms of MS are primary-progressive MS (PPMS) and progressive-relapsing MS (PRMS). Individuals with PPMS experience gradual deterioration from the onset without any symptom-free, or remittance, periods.

People with PRMS also have gradual disease progression from the start but may have occasional relapses.

The relapsing and progressive forms of MS typically follow different trajectories. With the progressive types of MS, symptoms build up and worsen over time. People with the relapsing form of the disease In experience worsening disability after a relapse. This is referred to as relapse-associated worsening (RAW) and is believed to be a significant cause of disability accumulation in patients with relapsing forms of MS. However, there is evidence that patients with RRMS also experience disability accumulation unrelated to relapses. This is referred to as progression independent of relapse activity (PIRA).

There is research on PIRA in early and established MS. However, predictors of PIRA measured at the occurrence of clinically isolated syndrome (the first episode of MS-related neurologic symptoms) have yet to be studied.

Carmen Tur

A research team led by Carmen Tur, M.D., Ph.D., from the Multiple Sclerosis Center of Catalonia Department of Neurology/Neuroimmunology at the Vall d’Hebron University Hospital in Barcelona, Spain conducted a longitudinal cohort study to examine the risk of PIRA after clinically isolated syndrome (CIS) occurs, potential predictors of PIRA, and the long-term outcomes of patients with PIRA. CIS is the first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or loss of the myelin that covers the nerve cells in the central nervous system. It can be a precursor to full-blown MS.

The study, which was published in the December 2022 issue of JAMA Neurology, included 1,128 participants with CIS who were assessed within three months of their first clinical episode. All participants were younger than 50; the average age was 32.1 years. PIRA was defined as disability accumulation confirmed by the Expanded Disability Status Scale (EDSS) at six months during a relapse-free period. Any disability accumulation episodes that did not qualify as PIRA were considered RAW.

Of the 1,128 participants, 37% experienced at least one episode of disability accumulation. Of these, 66% had at least one PIRA event, and 34% had RAW episodes. Of the patients who had PIRA, 31% did so within the first five years of CIS onset. Patients with early PIRA were older and showed a steeper increase in EDSS rate than those with late PIRA.

Tur and her colleagues found that about 8% of patients with MS could develop PIRA within the first five years of CIS onset. Older age was the only predictor of PIRA, with a 43% increase in risk for each decade older at the onset of CIS.

They concluded that PIRA is associated with adverse long-term outcomes, especially if events occur early in the disease. They suggest early identification of patients who will develop PIRA could improve treatment choices and lead to a better long-term prognosis.