This year’s FDA Update on Safety Issues in the Treatment of Rheumatic Diseases included updates about how the development of immunomodulators has impacted the treatment of COVID-19.
Nikolay P. Nikolov, MD, director, Division of Rheumatology and Transplant Medicine, U.S. Food and Drug Administration, shared an update about the FDA’s role in helping identify effective treatments for COVID-19. Dr. Nikolov was one of three members of the Division of Rheumatology and Transplant Medicine who presented the ACR Convergence 2020 session, which is available to registered attendees through March 11.
During his presentation that focused on general development consideration for immune-based therapies, Dr. Nikolov noted that as of the end of September, the FDA had allowed for more than 110 investigations into these kinds of therapies. Investigators have encountered several challenges, he said, including a rapidly evolving understanding of COVID-19’s natural history in both adults and children. In addition, the underlying inflammation is complex and still not well understood, including our understanding of when a protective inflammation becomes destructive.
“While there may not be a consensus, the prevailing view is that COVID-19-associated morbidity and mortality have been attributed to pathological host response and systemic hyperinflammation,” Dr. Nikolov said. “Inflammatory cytokines and biomarkers such as IL-1, IL-6, GM-CSF, TNF-alpha, C-reactive protein, and others have been found to be elevated in patients with more severe disease. Many of these inflammatory markers have become attractive targets for immunomodulation.”
A better understanding of COVID-19’s pathogenesis, manifestations, natural history, and immunopathology will bring more safe and effective therapies, Dr. Nikolov said. Finding meaningful scientific conclusions will require a multi-disciplinary approach and coordinated global, multi-stakeholder engagement to allow for the proper risk/benefit assessment of therapeutics with rigorous clinical trial data.
Raj Nair, MD, acting clinical team leader in the Division of Rheumatology and Transplant Medicine, opened the session with an overview of recently approved agents for rheumatic diseases.
New indications approved in 2020 included:
- Polyarticular juvenile idiopathic arthritis: Golimumab IV and tofacitinib. In addition, golimumab IV was also approved for treating psoriatic arthritis for those as young as 2 years of age.
- Non-radiographic axial spondyloarthritis: Secukinumab and ixekizumab.
- Adult-onset Still’s disease: Canakinumab.
- Progressive chronic fibrosing interstitial lung diseases with progressive phenotype: Nintedanib.
Biosimilars approved since late 2019 mentioned by Dr. Nair were two biosimilars to Humira, Abrilada (adalimumab-afzb) and Hulio (adalimumab-fkjp), one biosimilar to Remicade, Avsola (infliximab-axxq), plus Truxima (rituximab-abbs), which gained added approval for RA, granulomatosis with polyangiitis, and microscopic polyangiitis. More information about biosimilars can be found at www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars.
Among the first-time generic approvals for 2020 were naproxen and esomeprazole magnesium delayed-release tablets, 375mg/20mg and 500mg/20mg, for symptomatic arthritis relief to decrease risk of developing naproxen-associated gastric ulcers and meloxicam capsules, 5mg and 10mg, for osteoarthritis management. More information is available at www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals.
Amit Golding, MD, PhD, medical officer, Division of Rheumatology and Transplant Medicine, U.S. Food and Drug Administration, reviewed some of the recent safety-related issues and labeling updates of interest to rheumatologists.
While there were no changes in labeled warning and precautions involving hydroxychloroquine, the drug was in the news because of its use with some COVID-19 patients. Dr. Golding noted that the FDA cautioned against the use of HCQ or chloroquine (CQ) for COVID-19 outside of a hospital setting or clinical trial because of the risk of heart rhythm problems. But this does not affect the already FDA-approved uses for malaria, lupus, and rheumatoid arthritis.
“The benefits of HCQ/CQ outweigh the risks at the recommended doses for FDA-approved indications of treating autoimmune conditions,” Dr. Golding said.
Dr. Golding also provided updates on other drugs:
- Belimumab: Labeling was updated to add “and sometimes fatal” to now say “serious and sometimes fatal infections.” The mortality warning was removed.
- Abatacept: Labeling was updated to include a warning for angioedema as early as after the first dose, but also with subsequent doses.
- Baricitinib: Multiple reports identified within the FDA Adverse Event Reporting System during a surveillance summary review led to new labeled warnings about hypersensitivity and serious reactions such as angioedema, urticaria, and rash.
- Gabapentin and pregabalin: Case reports, human studies, and animal studies led to this new labeled warning concerning serious breathing problems for patients with respiratory risk factors.