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How common are ALS plateaus and reversals?
Richard S Bedlack1, Timothy Vaughan2, Paul Wicks2
1From the Department of Neurology (R.S.B.), Duke University and Durham VA Medical Center, Durham, NC; PatientsLikeMe (T.V., P.W., J.H.), Cambridge, MA; Massachusetts General Hospital (E.S., R.S., E.A.M., D.S., M.C., A.S.), Boston; and Harvard Medical School (E.A.M.), Boston, MA. Bedla001@mc.duke.edu.
Plateaus and minor improvements in amyotrophic lateral sclerosis (ALS) are common over short periods. These findings suggest that stable disease should not be mistaken for a treatment effect, while significant, sustained reversals warrant further investigation.
Area of Science:
- Neurology
- Clinical Trials
- Biostatistics
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
- Understanding disease progression variability is crucial for interpreting clinical trial outcomes.
Purpose of the Study:
- To quantify the frequency of disease plateaus and reversals in ALS patients.
- To analyze these patterns using data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.
Main Methods:
- Analysis of Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and ALSFRS-revised (ALSFRS-R) data.
- Calculation of plateau frequencies over 6-, 12-, and 18-month periods.
- Assessment of reversal frequencies and durations.
Main Results:
- 25% of participants showed no decline over 6 months; 7% showed no decline over 18 months.
- 14% experienced short-term improvements (positive ALSFRS-R slope).
- Fewer than 1% had sustained improvements of 4+ points for 12 months.
Conclusions:
- Disease stabilization and minor improvements in ALS are frequent, particularly over shorter durations.
- These fluctuations should not be misconstrued as treatment efficacy.
- Significant, long-lasting improvements are rare and merit further research.
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