CHICAGO — Anti-TNF biologic therapies are typically used first foradults aged 60 years or older with rheumatoid arthritis (RA), but many will need to switch to non-TNF biologics because of inadequate response or adverse effects. Although the infection risk associated with anti-TNF therapy is well established, less is known about the safety of non-TNF therapies initiated after anti-TNF exposure in this age group.

New data presented at American College of Rheumatology (ACR) 2025 Annual Meeting examined the risk for serious infection (SI) associated with starting non-TNF biologics after anti-TNF therapy in patients with late-onset RA (LORA) compared with patients with younger-onset RA (YORA). Age-related immune changes and distinct disease characteristics may increase infection risk for patients with LORA, which was defined for this study as receiving an RA diagnosis at the age of 60 years or more.

Lead researcher Jiha Lee, MD, a rheumatologist with the University of Michigan, Ann Arbor, Michigan, noted that about 40% of the RA population in the US is at least 65 years old, and the RA prevalence in that age range is 4% vs just 1% in the 18- to 49-year-old group. Patients with LORA have more acute onset, more systemic features, more large/proximal joint involvement, and worse outcomes, she said.

In this study, 198 patients with LORA who had started a non-TNF biologic/targeted synthetic disease-modifying antirheumatic drug (DMARD), identified from the Data Forward Database from 2001 to 2019, were propensity score-matched to 675 weighted patients with YORA. Lee explained that it’s challenging to find data on older adults with RA because clinical trials often exclude them.

SI in the study was defined as an infection requiring intravenous antibiotics and/or hospitalization or resulting in death within 12 months of the index date. It was considered an SI attributable to subsequent therapy if it occurred during treatment or within 3 months of stopping treatment; this was extended to 12 months for rituximab. Patients with other rheumatic diseases, cancer, or HIV before the first SI were excluded from the study.

No SI Risk Differences Between Age Groups

The researchers found that the risk for SI did not differ by age of RA onset or by treatment received (abatacept vs other non-TNF therapies). But several factors were independently associated with increased SI risk: having a prior SI, recent long-term glucocorticoid use, and higher Health Assessment Questionnaire (HAQ) disability scores. SI risk was associated with more modifiable factors.

“That means for us as rheumatologists that we should prioritize DMARD optimization and also limit steroids,” Lee said. Additionally, it’s important to improve frailty and build resilience for better function in older patients, she said, and improve vaccination rates.

Elena Schiopu, MD, professor in the Division of Rheumatology at the Medical College of Georgia at Augusta University, Augusta, Georgia, told Medscape Medical News that studying the effects of these drugs on older patients with RA is important for a number of reasons.

“Since the first biologics were approved, we haven’t had a good understanding of what sequential biologics could do to the immune system,” Schiopu said. “As we age, our immune system shifts, and the system is not as effective. We’re getting into that immune senescence, and patients are becoming more autoinflammatory. We see more infections, we see more inflammation, more RA refractory to regular therapies.”

 She said the findings underscore the risk posed by long-time use of glucocorticoids. “We know glucocorticoids are bad. It’s another signal to wake up and stop the steroids as soon as possible,” she said.

Schiopu also praised the use of the HAQ score, which is developed from patient-reported outcomes and includes questions about daily activities such as getting in and out of the car, eating, and washing. High scores were found to be associated with greater risk of serious infection, and she said the HAQ score is “one of the best ways to see how patients are doing.”

Gaps in Knowledge About Sequential Therapies

The research helps answer “one of the most important questions today,” Schiopu said. “Our patients with rheumatoid arthritis are getting older; we live in this era of biologics, and we wonder how safe it is to give them biologics. A lot of rheumatologists struggle with that. This particular paper shows that older patients aren’t going to get as many infections as you thought with second-line biologics, but stop the darned prednisone.”

“I think there is big black hole in our knowledge about sequential therapies,” Schiopu said. She added that future work should look at patients who have been on multiple biologics.

“If they were diagnosed in the ’90s, there’s a good chance they’ve been on quite a few biologics,” she said, adding that analysis of those scenarios would help educate rheumatologists on the best sequential therapies.

Lee and Schiopu reported no relevant financial disclosures.

Marcia Frellick is an independent, Chicago-based healthcare journalist and a regular contributor to Medscape Medical News.