November 10-15

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ACR Convergence 2023

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Studies result in new, updated FDA safety warnings


3 minutes

Rachel L. Glaser, MD
Rachel L. Glaser, MD

Monday’s FDA Update: Safety Issues in the Treatment of Rheumatic Diseaseprovided updates on rheumatology drug approvals, safety issues, and new initiatives that affect drug approval.

Rachel L. Glaser, MD, Clinical Team Leader, Division of Pulmonary, Allergy, and Rheumatology Products for the FDA, reviewed the results from the PRECISION trial, a study of cardiovascular (CV) safety in osteoarthritis or rheumatoid arthritis patients with or at high risk for CV disease that compared celecoxib with naproxen and ibuprofen.

“Celecoxib prescribing information was updated, with the conclusion that celecoxib 100mg twice daily was non-inferior to naproxen 375-500mg twice daily and ibuprofen 600-800mg three times daily for the composite endpoint of the Antiplatelet Trialists’ Collaboration,” Dr. Glaser said.

The boxed warning for CV thrombotic events with NSAIDs has been retained, she added, and the recommendation to use the lowest effective dose for the shortest duration possible to minimize the potential for adverse CV event was unchanged.

She also updated attendees on new data from the CARES study on cardiovascular outcomes in patients treated with febuxostat, a drug initially approved in February 2009 for treatment of hyperuricemia in patients with gout, versus allopurinol.

“For the composite primary MACE endpoint, febuxostat was non-inferior to allopurinol, with an HR of 1.03; however, all-cause and CV mortality were higher in the febuxostat group than in the allopurinol group,” she said.

The CARES study results led to a citizen’s petition to the FDA requesting removal of all medications containing febuxostat from the market. The FDA is reviewing the CARES study, and an advisory committee of external experts is planned in early 2019 to discuss the trial results and the results of the FDA review.

Dr. Glaser also provided updates on two topics previously discussed at ACR: Codeine restrictions for children and gadolinium-based contrast agents (GBCA) safety labeling.

The FDA has expanded the restrictions to limit the use of prescription cough and cold medicines containing codeine or hydrocodone to adults 18 years and older. Safety information about the risks of misuse, abuse, addiction, overdose, death, and slowed or difficulty breathing was added to the boxed warnings for these products.

Regarding GBCAs, Dr. Glaser noted that there have been prior drug safety communications addressing the retention of gadolinium in the brain and other tissues after the use of GBCAs for MRI.

In December, FDA required updated labeling to include a new class warning for GBCAs, and new patient medication guides were approved for all GBCAs.

“The FDA is also requiring manufacturers of GBCAs to conduct human and animal studies to further assess the safety of these contrast agents,” she said.

She wrapped up with an update on the FDA’s patient-focused drug development program.

“Patients are experts in what it is like to live with their condition, and are uniquely positioned to inform the understanding of the therapeutic context for drug development and evaluation,” she said, adding that two rheumatology-focused meetings were held in the last year.