“Hydroxychloroquine was used in the setting of COVID-19 at the beginning of the pandemic due to its purported potential antiviral and immunomodulatory properties,” Dr. Golding said. Patients were prescribed the drugs for either treatment or prophylaxis before their efficacy or safety could be determined. The reports “indicated that cardiac effects like cardiomyopathy and QT prolongation were a significant safety concern in the setting of COVID-19, which is substantially different from that of SLE or RA.”
The FDA issued a reminder about the known cardiac effects of hydroxychloroquine and chloroquine, including cardiomyopathy and QT prolongation, and cautioned against their use in COVID-19 treatment outside of the hospital setting due to increased arrythmia risks.10 No label changes were made for patients already taking either drug for their FDA-approved indications to treat autoimmune diseases, and they should continue therapy as prescribed, because the benefits of these medicines outweigh the risks in these patients, Dr. Golding said.
Belimumab’s labeled warnings and precautions were changed to include risk of sometimes fatal infections, and a previous mortality warning was removed. These changes were based on results of a post-marketing, long-term safety trial.11 The 52-week, randomized, placebo-controlled trial included 4,003 patients age 5 or older. Overall mortality was low and the number of serious infections was similar in both the belimumab and placebo groups, but more deaths were associated with infection in patients treated with belimumab. The trial’s results also showed a trend toward increased risk of serious depression in patients on belimumab, similar to earlier trials, Dr. Golding noted.
In the past year, the FDA approved several new indications for drugs to treat rheumatic diseases, including pediatric conditions.
In June, the FDA added angioedema to the hypersensitivity labeled warnings for abatacept based on the results of a 10-year review of serious, unlabeled adverse events in pediatric patients that included the case of a 16-year-old girl who developed a serious angioedema after her fifth dose of abatacept. This led to a full safety pharmacovigilance review that found 83 other angioedema cases in both children and adults on the drug, including some occurring just hours after infusion.12 The FDA changed the label warning and recommended continued safety monitoring of abatacept.
In July, the warnings and precautions label for baricitinib, a Janus kinase inhibitor, was changed to include hypersensitivity and serious reactions after the FDA became aware of multiple cases of rash, urticaria and angioedema observed in patients during post-marketing surveillance.13 The FDA also updated the labels for gabapentin and pregabalin to include a warning about respiratory depression in patients who take gabapentin or pregabalin and have other respiratory risk factors, such as the use of central nervous system depressants or opioids.14 Patients with chronic obstructive pulmonary disorder and elderly patients are also at increased risk, he said.
