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Clinical Trial
. 2016 Mar 1;86(9):808-12.
doi: 10.1212/WNL.0000000000002251. Epub 2015 Dec 9.

How common are ALS plateaus and reversals?

Richard S Bedlack  1 , Timothy Vaughan  2 , Paul Wicks  2 , Jamie Heywood  2 , Ervin Sinani  2 , Roger Selsov  2 , Eric A Macklin  2 , David Schoenfeld  2 , Merit Cudkowicz  2 , Alex Sherman  2
Affiliations
Clinical Trial

How common are ALS plateaus and reversals?

Richard S Bedlack et al. Neurology. .

Abstract

Objective: To determine the frequency of amyotrophic lateral sclerosis (ALS) plateaus and reversals in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.

Methods: We analyzed Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and ALSFRS-revised (ALSFRS-R) data from PRO-ACT participants. The frequencies of participants experiencing plateaus (periods where scores did not change) were calculated over 6-, 12-, and 18-month epochs. The percentage of participants ever experiencing reversals (periods where scores improved) of different lengths were also calculated and plotted.

Results: Over 6 months, 25% of 3,132 participants did not decline. Over 12 months, 16% of 2,105 participants did not decline. Over 18 months, 7% of 1,218 participants did not decline. Small ALS reversals were also common, especially over shorter follow-up intervals; 14% of 1,343 participants had a 180-day interval where their ALSFRS-R slope was greater than zero. Fewer than 1% of participants ever experienced improvements of 4 or more ALSFRS-R points lasting at least 12 months.

Conclusion: ALS plateaus and small reversals are common, especially over brief intervals. In light of these data, stable disease, especially for a short period of time, should not be interpreted as an ALS treatment effect. Large sustained ALS reversals, on the other hand, are rare, potentially important, and warrant further study.

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Figures

Figure 1
Figure 1. Natural history of amyotrophic lateral sclerosis progression in PRO-ACT
These histograms show the natural history of Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) participants' Amyotrophic Lateral Sclerosis Functional Rating Score (ALSFRS) changes at intervals of 6 months (A), 12 months (B), and 18 months (C).
Figure 2
Figure 2. Closer look at amyotrophic lateral sclerosis reversals
These graphs show 2 individual Pooled Resource Open-Access ALS Clinical Trials participants' Amyotrophic Lateral Sclerosis Functional Rating Score–revised (ALSFRS-R) scores over time. The portion of the curve picked up as an amyotrophic lateral sclerosis reversal is highlighted. Some of these reversals appear to be the result of a single data point (participant A, last data point). Others include multiple incrementally improving data points, which are potentially more interesting (participant B).
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