As the scope of the coronavirus pandemic broadens, it is only natural for people to look to the scientific and research communities for solutions. In recent weeks, however, the thirst for viable treatment options has contributed to drug shortages and misinformation for patients with rheumatic diseases.
Two cases in point involve hydroxychloroquine and ibuprofen. Laura L. Tarter, MD, and Daniel Hal Solomon, MD, MPH, of the Brigham and Women’s Hospital’s Division of Rheumatology, Inflammation and Immunity offer their perspectives on each of these issues, which carry significant implications for rheumatic care during this health crisis.
Fears Over Hydroxychloroquine Shortages
On March 17, a study was published in the International Journal of Antimicrobial Agents (Gautret et al.) concluding that “hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.”
The growing public interest in hydroxychloroquine has since led to reported shortages of the drug. This is a major concern for rheumatologists and their patients, as hydroxychloroquine is the gold standard therapy for systemic lupus erythematosus and used in treating such other rheumatic diseases as rheumatoid arthritis.
“We want everyone with lupus to be on hydroxychloroquine unless there’s a reason they can’t be,” said Dr. Tarter, who primarily treats lupus patients. “Hydroxychloroquine has been clinically proven to decrease the risk of organ damage and progression of disease. If you withdraw it, the risk of flare is 50 percent higher and the risk of severe flare is six-fold higher.”
The rising demand for hydroxychloroquine is particularly worrisome for Dr. Tarter because many experts have noted flaws in the Gautret study. For example, a recent article in Annals of Internal Medicine co-authored by Brigham rheumatologist Jeffrey A. Sparks, MD, pointed to “potentially substantial confounders” in the study along with “serious questions about scientific validity” due to “the handling of patients who were lost to follow-up.”
The lack of hard data currently available, Dr. Tarter said, means it is too soon to draw conclusions about the efficacy of hydroxychloroquine in treating—or preventing—COVID-19. She added that while hydroxychloroquine is well-tolerated at the typical daily dosage for lupus patients (200–400 mg), some COVID-19 protocols start at 600–800 mg.
“At higher doses and with concurrent administration of other medications such as azithromycin, the risk of prolonged QT interval may be increased,” she said.
Dr. Tarter advised that clinicians wait until the results of ongoing studies are published before prescribing hydroxychloroquine for COVID-19 treatment or prophylaxis. In the meantime, she said, the medical community and manufacturers who have committed to stepping up production of hydroxychloroquine should ensure that enough of the drug is set aside for lupus patients.
Addressing Safety of Ibuprofen/NSAIDs in COVID-19 Patients
On March 14, France’s health minister, Olivier Véran, tweeted that NSAIDs such as ibuprofen may exacerbate coronavirus-related symptoms. He recommended that patients instead take acetaminophen (known as paracétamol in France). A study subsequently published in The Lancet (Fang, et al.) suggested that ibuprofen could worsen disease for people with COVID-19.
These and other news items have led to widespread questions about whether ibuprofen and other NSAIDs are safe in COVID-19 patients — and even whether NSAIDs increase the risk of developing the disease. The issue is particularly important for rheumatologists, as about half of patients with severe arthritis use NSAIDs regularly or intermittently, according to Dr. Solomon. He wants to make it clear that concerns over NSAIDs at this time are unfounded.
“I don’t want to be overly critical; everybody’s grasping for straws with respect to COVID,” he said. “But I’ve seen no published data regarding NSAIDs and COVID, just published opinions.”
As Dr. Solomon explained, the authors of the Lancet article looked at associations between medicines and comorbidities in patients who develop COVID-19, suggesting there may be some risk factors for people who get the disease.
“However, when studying small numbers of patients, as is the case with this study, these associations—which I’d call ‘initial impressions’—may be misleading,” he said. “They’re not at all specific about NSAIDs.”
For the time being, Dr. Solomon advised physicians to take a “business-as-usual” approach to patient care. That is, arthritis patients who find relief from NSAIDs should continue to take these medications. Any patients who develop symptoms that could be related to COVID-19 or the flu should first try acetaminophen. If that doesn’t provide relief, the physician should then recommend switching to an NSAID—unless the patient has certain contraindications, such as cardiac, kidney or liver disease or poorly controlled hypertension.
“It’s really a stretch to suggest patients shouldn’t be taking NSAIDs because of the pandemic,” he said.
Dr. Solomon added that physicians should communicate to patients that anti-inflammatory drugs are not immunosuppressive and thus are safe to take in the face of COVID-19.