FDA officials ‘excited’ about new rheumatology drugs, but offer warnings

While the FDA approved a number of therapeutic agents for patients with rheumatologic diseases in 2020, safety signals such as angioedema and drug hypersensitivity have emerged, according to presenters at ACR Convergence 2020.

Raj Nair, MD, and Amit Golding, MD, PhD, both of the Division of Rheumatology and Transplant Medicine at the FDA, covered topics pertaining to safety and adverse events across the spectrum of the rheumatology armamentarium.

“Our division has approved several drugs for numerous new indications,” Nair said.

Some of those indications include the expansion of golimumab (Simponi, Janssen) injection in juvenile psoriatic arthritis and polyarticular juvenile idiopathic arthritis and pediatric PsA; tofacitinib (Xeljanz, Pfizer) for JIA; and canakinumab (Ilaris, Novartis) for adult-onset Still’s Disease.

In addition, secukinumab (Cosentyx, Novartis) and ixekizumab (Taltz, Eli Lilly & Co.) have been approved for axial spondyloarthritis, while nintedanib (Ofev, Boehringer Ingelheim) received an indication for certain types of interstitial lung disease.

Boxed Warnings, Post-marketing Studies

Looking closer at specific safety events for these medications, golimumab IV contains warnings and precautions for serious infections, invasive fungal infections, hepatitis B reactivation, malignancies and congestive heart failure, among others.

Serious infections are also part of the boxed warning for tofacitinib in JIA, along with thromboembolic events and gastrointestinal perforations. Patients taking tofacitinib should also avoid live vaccinations, according to Nair. “The FDA is requiring that a long-term observational safety study be conducted in pediatric patients 2 to 17 years of age with polyarticular juvenile idiopathic arthritis treated with tofacitinib to evaluate for the risks of malignancies, serious infections including opportunistic infections, deep vein thrombosis and effects on growth,” Nair said.

Infections such as tuberculosis, along with IBD and hypersensitivity reactions are associated with both secukinumab and ixekizumab, while canakinumab contains warnings for infections and live vaccines.

The FDA has offered warnings for hepatic impairment, thromboembolic events and GI perforations, among other events, for nintedanib but “removed language for black and African American patients” for belimumab, according to Nair. While encephalopathy, hypersensitivity reactions, depression and suicidality have been reported for belimumab, “no new safety signals were identified” for the drug this year, he said.

In addressing the approval of two biosimilar products for adalimumab (Humira, Abbvie), one each for infliximab (Remicade, Janssen) and rituximab (Rituxan, Genentech), and multiple generic products, Nair expressed optimism for the rheumatology community. “We have several new drugs approved for rheumatic diseases this year,” he said. “We are excited.”

Ongoing Story of Hydroxychloroquine

Picking up the thread, Golding zeroed in on “a variety of safety issues” that emerged at the FDA this year, largely focusing on cardiovascular issues with hydroxychloroquine and chloroquine, along with respiratory concerns with gabapentinoids.

Cardiovascular toxicity, cardiomyopathy and QT prolongation with hydroxychloroquine have become “significant safety concerns in the setting of COVID-19” according to Golding. “The FDA has issued a drug safety communication.”

In April, the FDA cautioned that hydroxychloroquine should not be used outside of a hospital setting, and the communication was updated in July. That said, while the association between hydroxychloroquine and QT prolongation have persisted, many patients with this outcome had also been taking “one or more drugs” such as azithromycin associated with a prolonged QT interval, Golding said.

“Importantly for this audience, patients taking hydroxychloroquine or chloroquine for approved indications like rheumatoid arthritis or systemic lupus erythematosus should continue taking these medicines as prescribed,” Golding said. “There is no change for the labeled warnings.”

Regarding gabapentinoids, a communication regarding respiratory depression was added in April. The FDA stipulated that this warning applied in cases with or without concomitant use of CNS depressants, according to Golding.

Beyond these associations, Golding cited data looking at belimumab for overall mortality and serious infections, among other outcomes. “The overall mortality was low and not different between the placebo and belimumab arms of the study,” he said. “Similarly, the overall number of serious infections was similar in placebo and belimumab.”

However, mortality associated with infections was higher in the belimumab arm, according to Golding. “Based on this trial, the product labeling was updated in September,” he said.

In terms of new safety signals, a 10-year, post-marketing surveillance study of abatacept (Orencia, Bristol Myers Squibb) yielded 83 cases of serious angioedema. This signal, then, was “added to the label” of abatacept as of June, Golding said.

In other new safety signal data, an ongoing post-marketing study of baricitinib revealed incidence of drug hypersensitivity. This outcome has since been added to the list of warnings and precautions for this drug, along with rash, angioedema and other events.