Kory, Pierre MD
Ivermectin, A Reanalysis of the Data
To the Editor:
Our article entitled “Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19” was recently published in the American Journal of Therapeutics.1 Our article included randomized and observational trial meta-analyses on the efficacy of ivermectin for the prophylaxis and treatment of COVID-19. Recently, the study conducted by Elgazzar et al2 has come under scrutiny with accusations of scientific misconduct. His paper was apparently retracted without his knowledge and without giving him the opportunity to defend these serious claims. This situation is most unfortunate. While this issue is being resolved, we decided to redo the original meta-analyses excluding this study. The summary point estimates were largely unaffected when the study by Elgazzar et al was removed. The revised forest plots are provided below (Figures (Figures11–3).
Original article by Kory et al. published in American Journal of Therapeutics: May/June 2021 – Volume 28 – Issue 3 – p e299-e318
After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials.
Areas of Uncertainty:
The majority of trialed agents have failed to provide reproducible, definitive proof of efficacy in reducing the mortality of COVID-19 with the exception of corticosteroids in moderate to severe disease. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. Given some have not passed peer review, several expert groups including Unitaid/World Health Organization have undertaken a systematic global effort to contact all active trial investigators to rapidly gather the data needed to grade and perform meta-analyses.
Data were sourced from published peer-reviewed studies, manuscripts posted to preprint servers, expert meta-analyses, and numerous epidemiological analyses of regions with ivermectin distribution campaigns.
A large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. Multiple, large “natural experiments” occurred in regions that initiated “ivermectin distribution” campaigns followed by tight, reproducible, temporally associated decreases in case counts and case fatality rates compared with nearby regions without such campaigns.
Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified.