It is time to stop using ineffective Covid-19 drugs such as ivermectin, metformin and fluvoxamine to treat infected patients .
Prof Salim Abdool Karim, former head of the Covid-19 ministerial advisory committee, has reflected his views on the use of non-efficacious treatments in an editorial published in the latest edition of The New England Journal of Medicine.
Abdool Karim, a renowned infectious diseases epidemiologist, says there are no evidence-based grounds to continue prescribing ivermectin and fluvoxamine when other effective treatments are available for patients with non-severe Covid-19.
“Prescribing non-efficacious treatments is not a neutral or harmless option. In addition to denying patients the appropriate treatment, such prescribing can lead to side effects without any therapeutic benefit and to drug shortages for patients who need the medications for other conditions.”
Abdool Karim said during the Covid-19 pandemic, some of the early treatment trials were rushed, leading to studies that were badly conducted or had too few patients.
“As a result, initial evidence of the efficacy of some Covid-19 treatments could not be replicated, but these drugs were already in widespread use by then, and some clinicians have been reluctant to change to proven efficacious alternatives.
“Ivermectin and fluvoxamine, in particular, are still widely prescribed, even though evidence has been steadily accumulating to indicate that both treatments at acceptable doses are not effective for Covid-19.”
Prescribing non-efficacious treatments is not a neutral or harmless option. In addition to denying patients the appropriate treatment, such prescribing can lead to side effects without any therapeutic benefit and to drug shortages for patients who need the medications for other conditions.
— Prof Salim Abdool Karim
Findings of a study conducted by researchers, also published in The New England Journal of Medicine, show the results of the Covid-Out randomised, controlled trial of oral metformin, ivermectin and fluvoxamine for the early treatment of infection in 1,323 outpatients.
“The investigators found no reductions in hypoxaemia, emergency department visits, hospitalisation, or death associated with any of the three drugs.
“A strength of the trial is the selection of adults between the ages of 30 and 85 years who were at high risk for severe Covid-19 because of overweight status or obesity.
“However, as a result, the trial may not be readily generalisable to patients at lower risk for severe disease.
“One secondary analysis, which should be interpreted with caution, suggested that metformin may reduce a composite of emergency department visit, hospitalisation or death in this population with overweight or obesity, a finding that indicates no more than the need for further investigation at this time.”
Abdool Karim said when the trial was initiated in 2020, evidence on the three treatments was either unavailable or equivocal.
“Since then, data has been accumulating from several clinical trials, including meta-analyses of metformin, ivermectin and fluvoxamine.
“In a combined analysis of anti-diabetic agents involving more than 3-million patients with diabetes and Covid-19 in 24 observational studies and 110 patients in one clinical trial, the investigators found that the use of metformin before hospital admission, but not in-hospital use, correlated with reduced mortality.
“In a meta-analysis of fluvoxamine involving 2,208 outpatients with non-severe cases of Covid-19 in three trials, investigators found that those who received fluvoxamine did not have a lower incidence of hospitalisation, mechanical ventilation or death than those in the control groups.”
He said for ivermectin, a meta-analysis of 16 trials involving 2,407 patients with both severe and non-severe illness showed no reliable evidence of reductions in mechanical ventilation, hospital admission, duration of hospitalisation, clinical severity or mortality; in addition, the investigators found no effect related to the dose of ivermectin.
Abdool Karim questioned how much evidence of non-efficacy is enough.
“The treatment guidelines of the World Health Organisation (WHO) provide a barometer for such decisions that is based on the latest evidence (as interpreted by experts from many countries) to provide recommendations regarding each candidate drug, with an indication of the quality of its evidence.
The most recent WHO guidelines, which do not include the results of the Covid-Out trial, stipulate explicit recommendations against the use of fluvoxamine and ivermectin but provide no recommendation with respect to metformin.
“The guidelines also provide explicit recommendations regarding treatments that should be prescribed.
“Despite this WHO guidance, drugs with unproven efficacy against Covid-19 continue to be prescribed by some physicians.”
Abdool Karim said the results of the Covid-Out trial provide “persuasive additional data that increase the confidence and degree of certainty that fluvoxamine and ivermectin are not effective in preventing progression to severe disease.
“In keeping with evidence-based medical practice, patients with Covid-19 must be treated with efficacious medications; they deserve nothing less.”
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