On-treatment relapse drives disability accrual in MS patients

By Lucy Piper

Frequent relapse activity appears to be a key driver of disability accrual in patients with relapse-onset multiple sclerosis (MS), indicates a study of patients receiving first-line injectable disease-modifying treatment.

The researchers report that the effect was "profound", even for patients whose relapses occurred more than 14 years after diagnosis, and particularly for those who had poor on-treatment relapse recovery.

"In an era where numerous new therapeutic agents are available for the treatment of relapsing multiple sclerosis, and where treatment goals have shifted towards freedom from disease activity, this result supports treatment escalation particularly in those patients relapsing on first-line therapy to mitigate permanent disability accrual", say Vilija Jokubaitis (Royal Melbourne Hospital, Victoria, Australia) and colleagues.

Among 2466 study participants receiving first-line therapy (interferon-β or glatiramer acetate), who were on treatment for 83% of the 10-year follow-up, Expanded Disability Status Scale (EDSS) score increased by a median 1 point overall.

Factors predicting greater disability accrual included being male, which increased the EDSS score at 10 years by a median 0.26 points, and older age, with each 10-year increment in age increasing the EDSS score by a median 0.43 points.

By far the greatest effect was for relapse, where an annualised relapse rate of 1 increased the EDSS score over 10 years by a median of 1.26 points. Relapse occurring in the first 5 years increased the EDSS score by a median 0.62 points, while a relapse between 5 and 10 years was associated with 0.50-point increase.

Among the 79.8% of patients who reported at least one relapse while on treatment, an annualised relapse rate of 1 was associated with a 0.86-point increase in EDSS score. This compared with a marginal 0.05-point EDSS score increase for the same rate in the 27% reporting at least one off-treatment relapse.

The researchers note in Annals of Neurology that, while relapse recovery data were limited, they demonstrated that "one of the key mechanisms driving disability accrual is the predisposition towards poor relapse recovery".

Relapses failed to resolve in 58.1% of patients with clinically significant EDSS increases, compared with 34.4% of those who EDSS scores significantly decreased.

Treatment led to 34% of patients improving or remaining stable and cumulative exposure to first-line therapy protected against long-term disability. The researchers estimate that 11.6 years of treatment exposure, irrespective of type, could prevent 1 EDSS point increase.

But more protective than first-line treatment, by more than four times, was pregnancy in the first 10 years after starting treatment. Pregnancy was associated with a median 3.17-point lower EDSS score over 10 years, whereas comparable therapy exposure was associated with a median 0.71-point lower EDSS score.

"[T]hese results provide evidence and confidence in the long-term benefits of disease-modifying therapy and pregnancy in patients with active relapse-remitting multiple sclerosis, but further argue for treatment escalation in those patients relapsing on first-line therapy to protect against long-term disability accrual", the researchers conclude.

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