Reassessing Disease Control in Relapse-Free Patients

Key Takeaways:

• Nearly half of respondents with relapsing-remitting MS in the 2026 Multiple Sclerosis In America survey reported no relapses in the past year.
• In a nationwide cohort, relapse in the preceding year did not predict fatigue severity. Disability, processing speed, and mood did.
• A relapse count tracks new acute inflammatory activity, not function over time. Fatigue, cognition, gradual worsening of symptoms, and what a patient has stopped doing over time have to be asked about directly.

An MS patient who has not relapsed in a year meets the usual definition of controlled disease. In the 2026 Multiple Sclerosis In America survey, 47.6 percent of respondents with relapsing-remitting multiple sclerosis (MS) had gone a year without a relapse.¹ Asked about daily life, most of them describe symptomatology that the absent or low relapse count does not capture.

What relapse-free patients report

Fatigue dominates the open-ended responses about symptoms in relapse-free patients. They describe it less as tiredness than as a limit on how much of the day they can use. A respondent 20 years past diagnosis and currently on oral therapy wrote that she had left full-time work and could "no longer confidently drive long distances because of fatigue." Another, 16 years post-diagnosis and relapse-free, said relationships were harder to maintain "as fatigue gets worse throughout the day."¹ That pattern of worsening fatigue as the day progresses comes up repeatedly.

Cognitive changes are often reported in conjunction with fatigue. Patients may not identify changes in cognition as a symptom directly; they name it by what it costs them. One relapse-free respondent summed up 7 years of disease as being unable to work "due to extreme fatigue and memory issues." In patients with relapsing-forms of MS, 65.8 percent reported cognitive dysfunction in the past month.¹

Relapse-free respondents and those who had recent relapses name fatigue as their biggest daily challenge at similar rates. Relapse status does not separate the 2 groups on what they are dealing with day to day.

Where relapse counts fall short

The clinical literature also supports that recent relapses or relapse count do not predict fatigue. In a Swedish cohort of 2,165 patients with 3,213 fatigue measurements, a relapse in the past year moved the total fatigue score by 0.6 points after adjustment (95 percent confidence interval −2.0 to 3.2). The study's own threshold for a clinically meaningful difference is roughly 10 points. New cerebral lesions on MRI did no better, at 0.1 points (−2.1 to 2.3).²

What did predict fatigue severity were factors not captured by a simple relapse count: disability level, at 17.6 points between the highest and lowest strata; information processing speed, at 10.7 points between quartiles; and depression and antidepressant use, at 12.7 and 13.3 points.²

Many patients without recent relapses also have progression of clinical symptoms in the absence of new relapse or inflammatory activity, representing disability accrual that is not captured by relapse rate. Progression independent of relapse activity was identified in 33.9 percent of 33,303 patients with relapsing-remitting MS under a standardized definition.³

What drives MS fatigue

Fatigue in MS is reported in 52 to 90 percent of patients. It is multifactorial, with inflammatory, endocrine, and central contributions. A substantial share of it is secondary – driven by sleep disorders, depression, and medication effects – and that share is treatable in a way that MS-driven fatigue is currently not. It is therefore critical to identify and treat secondary causes of fatigue in MS patients who report significant fatigue. There is no objective measure and no validated biomarker, so assessment relies on patient-reported instruments such as the Modified Fatigue Impact Scale and the Fatigue Severity Scale.⁴

What to ask instead

Asking whether a patient has relapsed tells you solely about new inflammatory activity. Asking when in the day fatigue starts limiting what they can do, what they have stopped doing since the last visit or over the last year, and whether they still drive the distances they used to tells you more about function. Screening for depression and sleep disruption belongs in the same conversation, since both predict fatigue severity and both are treatable.

A patient with no relapses and no new lesions may be under excellent control with respect to new inflammatory activity, but they can still have significant, and even worsening, symptoms related to their MS that need to be monitored for, evaluated, and where possible, treated.