By: Evan S. Vista, MD, FPCP, FPRA
The primary lupus drug to prevent disease flare and currently prescribed for long term maintenance by rheumatologists is in critical short supply in our country and worldwide.
Hydroxychloroquine is taken by lupus patients who are usually young, pregnancy-bearing-age women on their most productive years. They rely on this essential drug to keep their disease inactive. The prospect of using hydroxychloroquine to treat Covid-19 amid the novel coronavirus pandemic has sparked heated debate among politicians and scientists. Prominently endorsed by US president Trump, there have been indications that the drug is effective in treating or preventing Covid-19, but the studies have not endured the due diligence of extensive clinical trials.
Hydroxychloroquine, an old drug, is a derivative of chloroquine that originates from a compound named quinine isolated from the bark of the cinchona tree by French chemists way back in 1820. In 1934, German scientists created the synthetic chloroquine as part of a class of anti-malarial. Touted for its relatively safety profile for long term use, hydroxychloroquine is the less-toxic version of chloroquine.
In the labs, hydroxychloroquine has demonstrated some efficacy against SARS Cov-2 responsible for the present pandemic. In-vitro data demonstrated its role in preventing viral loading and replication of the coronavirus. Studies on humans to date have presented conflicting conclusions and robust studies are highly warranted. Since 2006, it has not been recommended for use in severe malaria by the World Health Organization (WHO) because of problems with resistance, and it has been primarily used since then as a disease-modifying, anti-rheumatic drug classified by the American College of Rheumatology.
Aside from the drug’s widespread and approved use for lupus, it is used to treat other autoimmune diseases like rheumatoid arthritis, juvenile arthritis and some forms of connective tissue disease mainly acting as an immune modulator. The drug has demonstrated established efficacy and safety on the innate and adaptive immune system of the body in published studies, the system that runs on overdrive among critically ill covid-19 patients.
Since the pandemic erupted, hydroxychloroquine together with chloroquine has been explored for off-label use among moderate and severe Covid-19 patients and has been included among treatment guidelines in the Philippines and abroad based on the small and limited clinical data currently available.
When the US Food and Drug Administration issued an emergency use authorization to treat Covid-19 patients with the drug, the supply dramatically ran short versus the global demand. Stockpiling of the drug to the point of hoarding became an issue among countries and even individuals, compromising the continued care of patients with these rheumatic conditions. Current inventories of here and abroad are based on the proportional demand of these rheumatic disease patients thus, overwhelming the drug supply chain brought about by this pandemic.
Lupus patients routinely use the drug as a steroid sparer, the steroids being another main lupus medication with more toxic side effects, making hydroxychloroquine the preferred lupus drug for chronic therapy by rheumatologists. It is also the only known therapy for primary Sjogren’s syndrome, another autoimmune disorder.
The role of hydroxychloroquine for compassionate intake among sick Covid-19 patients is currently being widely utilized but using it to prevent or protect you from being infected is highly discouraged. This alarming practice contributes to the acceleration of worldwide run of the drug and promotes shortages of supply specially to developing countries like ours. While we await large scale clinical trials including the WHO initiated global solidarity study that includes hydroxychloroquine as part of the treatment arm, data to support the use of hydroxychloroquine and chloroquine for Covid-19 at the moment are inconclusive.
Unfortunately, reports of adverse events using inappropriate dosages and preparations have increased with the anti-malarial use. These drugs in acute use can cause heart rhythm abnormalities which may pose particular risk to critically ill persons especially on high doses.
It is our ethical obligation as physicians and researchers to organize and refer patients to expedited, well-performed randomized trials that can clarify the safety and efficacy for its potential for Covid-19 fight. Whereas, the evidence supporting the use of antimalarial medications for Covid-19 is equivocal, the evidence for the use of these drugs to treat immune-mediated diseases is not.
Hydroxychloroquine is a cornerstone of therapy for systemic lupus erythematosus. Major clinical trials have demonstrated that the withdrawal of hydroxychloroquine can lead to flares of the disease, including life-threatening manifestations, such as lupus nephritis (a severe form of kidney involvement) and higher incidence of thrombotic risk namely stroke or heart attack. The Philippine Rheumatology Association (PRA) has noted a sharp rise on queries from concerned patients who are having difficulty obtaining their medication.
Given the likelihood that shortages will continue in the near term, we propose that manufacturers, clinicians, pharmacies, health systems, and governmental health agencies continue to coordinate an aggressive response to ensure that antimalarial drug use is appropriately managed during the Covid-19 pandemic.
Among the two drugs used in Covid-19 fight, PRA advocates the use of chloroquine over hydroxychloroquine among hospitalized patients using our local treatment guidelines and following safety criteria parameters for its use. This enables rationing of supply for hydroxychloroquine among patients with rheumatic conditions. The pharmacokinetics of hydroxychloroquine are an important consideration in guiding the clinicians on its optimal dosage and use given the shortages experienced by these patients. The long half-life of the drug means that brief gaps in therapy, on the order of 1 to 2 weeks, are less concerning.
However, longer treatment lapses put patients at risk for disease exacerbations, given studies showing that lower blood levels of hydroxychloroquine correlates with more lupus disease activity. A higher incidence of lupus flares was seen as soon as 2 weeks after the drug was stopped were reported. Some patients may do better than others with this approach and it is important to communicate closely with your doctor by utilizing all possible means including non-contact, electronic consults for patients on long term maintenance use of this drug during this pandemic.
The looming public health crisis for people with rheumatic diseases who will be unable to obtain hydroxychloroquine is the result of a perfect storm of fear and dissemination of overpromised data. However, there is still time to mitigate the damage. Physicians should educate themselves about the strength of available data regarding antimalarials in treating Covid-19, and public figures should refrain from promoting unproven therapies to the public.
More than 20 trials are being carried out globally and Philippines will be able to participate. In the meantime, physicians should remember our sacred oath that first, we must do no harm and always practice sound clinical judgement with the use of these potentially life-saving drugs. We must also keep in mind our Filipino patients with rheumatic disease for whom high-quality evidence shows that hydroxychloroquine improves health.