During this period of great concern and social disruption due to the coronavirus pandemic, hydroxychloroquine (HCQ), sold under the brand name Plaquenil, has been a drug in the news. Anecdotal evidence has suggested that this drug might have some effect in limiting the severity of the COVID-19 disease caused by the coronavirus, but no high-quality data to confirm that have yet been reported.
What is HCQ, how does it work and how is it used in many patients with systemic lupus erythematosus (lupus) and some patients with rheumatoid arthritis, Sjogren’s syndrome and other rheumatologic disorders?
HCQ is one of a number of drugs used to maintain lupus and other rheumatic disease patients in a state of low disease activity. It is in a class of drugs called antimalarials. An earlier form of the drug, called chloroquine, was used widely by the US Army in the Pacific Theater during World War II to protect soldiers from malaria. Doctors observed that the drug lessened rheumatic symptoms in these soldiers. HCQ and other variants of the drug have been prescribed In one form or another to treat lupus since the 1940s.
Doctors and scientists still don’t completely understand how, precisely, these antimalarial drugs affect lupus. But, lupus and other rheumatic conditions are autoimmune diseases, and research shows that these drugs block certain immune pathways that are dysregulated in lupus. HCQ is an old-line drug that became a mainstay of rheumatologic treatment in a medical environment that had few choices. Its value for lupus treatment in mild to moderate disease endures, but the pharmaceutical options available today have become greatly expanded.
The goal of medically managing lupus is to first control disease activity – to try to bring a person’s condition into a state of remission through intensive treatment. The second goal is to maintain this low disease activity state and minimize any adverse effects of treatment.
Lupus can affect multiple organs in the body and can be mild or severe. It can also worsen or improve at different times without any obvious explanation. Rheumatologists use a diverse range of drug therapies to meet individual patients’ needs. Patients with mild disease are generally prescribed HCQ, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or low-dose glucocorticoids (steroids). People who have more active disease are treated with higher doses of steroids and more potent immunosuppressive drugs, such as mycophenolate, azathioprine, and cyclosporine. The latter are considered quite helpful in treating kidney disease related to lupus. For very severe disease that is organ- or even life-threatening, other treatments are used, including:
The last of these, biologics, include belimumab and a number of others that are under active study for lupus, such as anifrolumab, abatacept, epratuzumab, and atacicept. Rituximab is sometimes used in patients with lupus nephritis, although it is not FDA approved for that condition. Many more agents that target diverse aspects of the immune system are under investigation, and there are indications that more effective therapies with fewer toxic side effects may soon be available. Skilled rheumatologists use all available therapies to respond to changes in a patient’s disease activity and maintain optimal health. Thus, while HCQ is an important foundational drug for lupus, it is by no means the only effective agent for managing the disease.
The accepted evidence regarding the long-term use of HCQ to treat lupus was developed from several case report series over years of patient observation, culminating in a gold standard trial of HCQ vs. placebo reported in 1991. This meticulously designed research trial was conducted in five academic centers, lasted six months, and measured carefully defined study endpoints.
Patients with stable, mild disease who had been on HCQ for at least six months were randomized to continue on their HCQ or to receive placebo. There were no differences between the two randomized groups that could lead to skewed results from the trial. The trial was double-blind, meaning that neither patients nor their doctors knew who was receiving HCQ and who was receiving a placebo.
The trial showed no statistically significant difference in the time to a severe worsening of disease between those patients who stayed on their HCQ therapy and those who were given a placebo. While there were more clinical flare-ups over the course of the study in those patients receiving placebo, the notable differences that did develop between the two groups only started to appear after about nine weeks. The message provided by this well-respected study is that long-accepted scientific findings show that patients who are in a low and stable disease state can safely stop taking their medication for weeks at a time without major risk of a severe disease worsening.
Scientists and clinicians rely on the kind of research described above to make informed and safe recommendations for patient care. We will always work with our patients to optimize their condition and will suggest alternate medications to keep them healthy. Since the above study was published, additional, more potent drugs have become available, and these have been added to medication regimens to achieve better control of lupus and RA than ever before. As members of the American College of Rheumatology, all HSS rheumatologists join the collective effort to bring forth the best therapies through careful research and to advocate for the health of rheumatology patients nationwide every day.