Ardent Hopes Versus Proven Benefits: The Perils of Indiscriminate Antimalarial Prescription for COVID-19

By Andrew L. Concoff, MD, FACR, CAQSM

The potential of the antimalarials, hydroxychloroquine and chloroquine, to treat COVID-19 infection has generated significant enthusiasm.  The initial, nascent data that supports this notion comes in a variety of forms: clinical knowledge of the efficacy of these medications in treating other intracellular pathogens, in vitro data indicating a reduction in replication of SARS-CoV-2 after exposure to antimalarials, uncontrolled data from China indicating favorable outcome among hospitalized patients, and a small trial with substantial methodologic flaws that is, nonetheless, suggestive of benefit when used in association with azithromycin.  The excitement for this approach increased dramatically following a press conference wherein President Trump speculated that these medications may have a significant impact on the pandemic.  Widespread prescription of antimalarials has followed, both in controlled settings but also indiscriminate use in uncontrolled settings.  The result has been a shortage of hydroxychloroquine for those who rely upon these drugs for continuous use to treat autoimmune diseases.  In an extreme example, a patient reported having received a letter from her local pharmacy thanking her for the sacrifice associated with her accepting that her hydroxychloroquine would not be refiled so that it could be reallocated for use among those suffering with COVID-19.  The letter went on to provide reassurance by suggesting that the pharmacokinetics of the drug are such that she ought to expect no ill effects of being off the medication for some forty days.       

Antimalarial prescription has been applied to several COVID-19-related scenarios.  Its use has been suggested for prevention of COVID-19 infection, for prophylaxis among those asymptomatic but with exposure to someone who has tested positive for COVID-19, those that are only theoretically at risk by virtue of immunosuppressive medication use, as well as those more seriously infected, typically according to reseach protocols in hospital environments.  Conclusive evidence is lacking for their use in each of these circumstances.  Given the present limited supply of these medications, there is a risk in indiscriminate prescribing patterns.  Inadvertently, we may be shifting the available stock of these medications from those in whom it has long been demonstrated to bear significant effectiveness to a population among whom the medication has uncertain effectiveness.  For example, in the case of systemic lupus erythematosus (SLE), hydroxychloroquine has been demonstrated not only to reduce the likelihood of disease flares but also to reduce risk of mortality and, thus, has been recommended for all patients with SLE without a contraindication to its use.  Even more ominously, termination of hydroxychloroquine has been associated with an increased risk of mortality among those with SLE.  Finally, there is no evidence that the protective effects of hydroxychloroquine persist after discontinuation, much less for the forty days suggested in the letter referenced above.  Thus, the transition of the available stock of antimalarials away from patients with autoimmune disease is associated with significant hazard.

This is not to say that antimalarials should not be made available for appropriate use among those with COVID-19.  But in order to prevent a widespread shortage of the medication, the initial use of these medications for the pandemic of COVID-19 must be balanced by the needs of those who chronically rely on these medications to treat autoimmune diseases.  We cannot allow the horrors of the pandemic to lead us to overcommit limited resources, such as our supply of these antimalarial drugs, on the basis of ardent hopes for benefit in COVID-19 without consideration of the proven scientific benefit and hazards of withdrawal of these medicines in patients with autoimmune diseases. 

The advent of the COVID-19 pandemic has fundamentally changed the practice of Rheumatology. One way that we can face such uncertainty and confront these challenges is band together virtually, by sharing our thoughts and approaches.  Please send your concerns, solutions, thoughts, and novel approaches to info@unitedrheumatology.com. 

Stay safe, stay healthy, stay United. 

 

REFERENCES:

https://www.buzzfeednews.com/article/tanyachen/kaiser-permanente-lupus-chloroquine

Lupus Sci Med: first published as 10.1136/lupus-2019-lsm.299 on 1 April 2019. Downloaded from http://lupus.bmj.com/

Ann Rheum Dis 2007;66:1168–1172. doi: 10.1136/ard.2006.068676

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