The latest on new U.S. Food and Drug Administration (FDA) approvals of rheumatologic drugs since the last ACR Convergence, along with safety updates and considerations for T cell engagers, was presented in hybrid format with presenters on the East Coast appearing remotely and the audience in McCormick Place in Chicago during ACR Convergence 2025.
“We’ve had another busy year at FDA,” said Sunghye Kim, MD, Clinical Reviewer in the Division of Rheumatology and Transplant Medicine (DRTM) at the FDA. Dr. Kim discussed adult drugs during Rheumatology Update from the FDA on Tuesday afternoon.
“We’ve approved new indications for previously approved drugs,” she continued. “We have also approved new formulations of previously approved drugs and approved a new ophthalmic solution. New biosimilars and interchangeables were also approved this year.”
Recorded sessions at ACR Convergence 2025, including the FDA update, are available on demand to all registered meeting participants through October 31, 2026, by logging in to the meeting website.
New adult indications included inebilizumab for immunoglobulin G4-related disease (IgG4-RD), upadacitinib for giant cell arteritis (GCA), cyclobenzaprine sublingual tablets for fibromyalgia, and obinutuzumab for lupus nephritis.
Inebilizumab was initially approved for adults with neuromyelitis optica spectrum disorders (NMOSD) who are anti-aquaporin-4 antibody positive. Dosing is unchanged from the initial indication, with key warnings for effective contraception due to fetal risks and monitoring of immunoglobulin levels.
Upadacitinib was initially approved for adults and children with a wide range of rheumatologic diseases. The new approval adds GCA for adults. It can be used in combination with a tapering dose of corticosteroids or as monotherapy following discontinuation of corticosteroids.
The boxed warning for thrombosis has been updated to include upadacitinib as well as all other Janus kinase (JAK) inhibitors.
Cyclobenzaprine sublingual was first approved for muscle spasm associated with acute, painful musculoskeletal conditions. The new approval adds fibromyalgia.
Obinutuzumab was first approved for chronic lymphocytic leukemia and follicular lymphoma. The new indication adds adults with active lupus nephritis who are receiving standard therapy.
Acoltremon ophthalmic solution 0.003% is a first-in-class agent targeting thermoreceptors. The drug is intended to increase tear production to alleviate the signs and symptoms of dry eye. The most common adverse event is instillation site pain, reported by 50% of patients.
The agency also approved pegloticase for chronic gout in patients refractory to conventional therapy.
Biosimilar and interchangeable approvals include ustekinumab, tocilizumab, and adalimumab.
Two key post-marketing reviews of opioids reported earlier this year prompted key safety changes for long-term use, said Fernanda D. Young, MD, DRTM Medical Officer at the FDA. The data showed an increased incidence of prescription opioid misuse, abuse, and opioid use disorder, as well as fatal and nonfatal opioid overdose events in long-term use.
Among other changes, revised prescribing information:
- advises prescribers to avoid rapid dose reduction or abrupt discontinuation;
- emphasizes the association of increased risk of serious harm with higher doses; and
- requires prescribers to inform patients and caregivers about opioid overdose reversal agents naloxone and nalmefene.
Nonsteroidal anti-inflammatory warnings and precautions now include two new severe cutaneous reactions: fixed drug eruption (FDE) and a severe variant called generalized bullous fixed drug eruption (GBFDE). Both are rare, life-threatening, and have a latency period of minutes to hours after drug ingestion.
Dr. Young also detailed updated warnings for mycophenolic acid, mycophenolate mofetil/mycophenolate sodium (MMF/MPS), voclosporin, sulfamethoxazole-trimethoprim, adalimumab, and anakinra.
Pregnancy registry data for a number of biologics has become available, she continued, prompting pregnancy updates for golimumab, ustekinumab, and certolizumab pegol. Data to date do not show additional pregnancy risk for the three agents.
Dr. Young also emphasized the continuing danger of consumer products marketed as “natural” that actually contain active pharmaceutical ingredients not shown on the label. She cited a recent warning for Reuma King and Contra Reuma found to contain dexamethasone, diclofenac, and methocarbamol not listed on the product labels.
Multispecific immune therapies, drug or biologic constructs that bind to multiple different targets simultaneously, are moving from oncology to rheumatology. T cell engagers (TCEs) bind to at least one T cell target and one B cell target to promote T cell activation and B cell killing.
The goal of TCE therapy is deeper and wider B cell depletion than can be achieved by conventional therapies, said Emma Weeding, MD, MS, Medical Officer and Primary Clinical Reviewer for DRTM. The fewer potentially pathogenic B cells remaining, the more easily the body will repopulate naïve B cells to restore a self-tolerant, non-autoimmune state.
TCEs also have practical appeal. They are generally off-the-shelf products, unlike chimeric antigen receptor (CAR) T cells, which must be manufactured for each individual patient. And they are under intense investigation in rheumatology, which deals with so many B cell related diseases.
The problem is safety.
Dr. Weeding said that while TCEs have been approved in oncology, investigational work in rheumatology is in the very early stages. Safety and efficacy data are lacking.
Importantly, from the FDA perspective, oncology and rheumatology have very different risk-benefit profiles. Treatment-related risks that might be acceptable in a cancer trial would likely not be acceptable in a rheumatology trial.
“Due to the complexity of these products,” Dr. Weeding said, “our agency is very open and interested in having these (safety) conversations early in the drug development process to ensure and support a productive, streamlined, and completely successful drug development.”
Don’t Miss a Session
If you weren’t able to make it to a live session during ACR Convergence 2025 — or you want to revisit a session from the annual meeting — make plans to watch the replay. All registered participants receive on-demand access to scientific sessions after the meeting through October 31, 2026.