The WHO advises against the use of two drugs for non-severe COVID-19
Current evidence does not justify the use of colchicine to treat non-serious diseases, and fluvoxamine should not be used outside of clinical trials.
The antidepressant drug fluvoxamine and the gout drug colchicine are not recommended for patients with mild or moderate Covid-19 because there is currently insufficient evidence that they improve important outcomes for patients, and both drugs carry potential harms , says a Development Group of WHO Guidelines (GDG) international expert panel.
No recommendation was made for any of the drugs in severely or critically ill patients, as data are limited or non-existent.
Fluvoxamine and colchicine are commonly used inexpensive medications that have received considerable interest as potential Covid-19 treatments during the pandemic. However, today’s recommendations against their use reflect current uncertainty about how the drugs produce an effect on the body and evidence of little or no effect on survival and other important measures, such as the risk of hospital admission and the need for of mechanical ventilation. There is also a lack of reliable data on serious Covid-19-related harms associated with these drugs.
The WHO’s advice against the use of fluvoxamine , except in clinical trials, was based on data from three randomized controlled trials (RCTs) with more than 2000 patients, and its strong advice against colchicine was based on data from seven RCTs with 16,484 patients.
After carefully reviewing this evidence, the panel, which includes experts from around the world, including four patients who have had Covid-19, concluded that almost all well-informed patients would choose not to receive fluvoxamine or colchicine therapy for Covid-19 based on the evidence from available data.
The panel noted that none of the included studies enrolled children, so the applicability of these recommendations to children is uncertain. However, they did not see a reason why children with Covid-19 would respond differently to treatment with fluvoxamine or colchicine.
Today’s recommendations are part of a guide developed by the World Health Organization with the methodological support of the MAGIC Evidence Ecosystem Foundation , to provide reliable guidance on the management of Covid-19 and help doctors make better decisions with their patients.
The guidelines allow researchers to update previously vetted and peer-reviewed evidence summaries as new information becomes available.
Previously, the WHO made a strong recommendation for the use of nirmatrelvir and ritonavir , and conditional recommendations for sotrovimab, remdesivir and molnupiravir for high-risk patients with non-severe Covid-19.
For patients with severe Covid-19, WHO strongly recommends corticosteroids , in addition to IL-6 receptor blockers or baricitinib , but advises against the use of convalescent plasma, ivermectin and hydroxychloroquine in patients with Covid-19, regardless of the severity of the disease.
Clinical question : What is the role of medications in the treatment of patients with COVID-19? Context : The evidence base for therapy for COVID-19 is evolving with numerous randomized controlled trials (RCTs) recently completed and ongoing. This update adds new recommendations for fluvoxamine and colchicine in patients with non-severe COVID-19; the former was based on data from three RCTs with 2196 patients, and the latter on data from 10 RCTs with 17,914 patients. New recommendations : The Guideline Development Group (GDG) recommends against using fluvoxamine in patients with non-severe disease, except in the context of a clinical trial. A strong recommendation was made against the administration of colchicine in patients with non-severe disease. No recommendation was made in severely or critically ill patients, as there is limited or no data on any of the medications for this population. Several treatment alternatives are now available for non-severe COVID-19 patients at increased risk of hospitalization. In the absence of direct comparisons in trials, indirect comparisons from living network meta-analysis (LNMA) have been used to inform the use of one drug over another with a related mechanism of action. Options will depend on availability of medications, routes of administration (intravenous only for remdesivir ), medications co-administered, duration of treatment, and time from symptom onset to start of treatment in trials. Understanding the new recommendations : In moving from evidence to recommendations, the GDG considered a mix of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. In recommending against the use of fluvoxamine for patients with non-severe disease, except in the context of a clinical trial, the GDG recognized the lack of a clear mechanism of action supporting its efficacy, and low-to-moderate certainty evidence suggesting little or no no effect on hospitalization, mechanical ventilation and mortality. The panel also noted the absence of reliable data on related serious adverse events, known significant drug interactions, and the large proportion of drug discontinuations in the included studies. The panel did not anticipate significant variability in patient values and preferences regarding the use of fluvoxamine and therefore recommended against use of the drug except in the context of a clinical trial. In recommending against the use of colchicine for patients with non-severe disease, the GDG highlighted evidence showing little or no effect on hospitalization, mechanical ventilation and mortality (moderate certainty). The GDG also discussed the known risks of drug interactions and the narrow therapeutic window of colchicine, particularly in patients with or at risk of liver and kidney failure. Colchicine toxicity can be serious and sometimes fatal . |
