A SYSTEMATIC REVIEW WITH META-ANALYSIS ON THE EFFICACY OF RANDOMIZED CLINICAL TRIALS IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS USING THE FINAL SCORE ON THE AMYOTROPHIC LATERAL SCLEROSIS FUNCTIONAL RATING SCALE-REVISED AS THE OUTCOME MEASURE.

In recent years there has been a significant increase in clinical trials to discover new medications that can slow the progression of Amyotrophic Lateral Sclerosis. The objective of this study was to carry out a systematic review with meta-analysis of randomized clinical trials lasting six or more months to evaluate the efficacy of treatments in patients with Amyotrophic Lateral Sclerosis carried out between 2016 and 2021, using the final score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised. The search for articles covered the main databases in addition to the ClinialTrials.gov website and in the end, 18 studies were selected for analysis. In total, 4.214 participants were enrolled, 1.880 received the drug and 1.933 received the placebo, and about 30,0% discontinued over the course of the studies. The average age was 57 years old, with a predominance of males (65,0%) and 21,4% of participants had the onset of symptoms in the bulbar region and 77,0% in the spinal region. Reading the articles also revealed great clinical variability between patients. Of the 15 drugs that were tested, Edaravone, Relyvrio and Masitinib showed positive effects if they were administered before severe functional impairment. However, a recent study failed to achieve Relyvrio's primary goal of slowing the decline in ALSFRS-R scores compared with placebo. In the methodological analysis, two studies presented some concerns due to blinding, including only patients and investigators, and had high discontinuation rates. The funnel plot and Egger's regression test showed no publication bias. Subgroup analysis showed that substantial heterogeneity of the studies included in the analysis was significantly greater in the group of published articles as opposed to the unpublished studies.