JAK Inhibitors Remain a Viable Option for Older Adults With IBD

SAN FRANCISCO — Janus kinase (JAK) inhibitors appeared to be a safe, effective option for treating inflammatory bowel disease (IBD) in older adults, according to two poster presentations.

In the first one, Nicole Garcia, BA, of the University of California San Francisco (UCSF) reported that, during 2 years of treatment with tofacitinib (Xeljanz) or upadacitinib (Rinvoq), no major adverse cardiovascular events (MACEs) occurred among 109 patients. Then in a companion poster, Yuntao Zou, MD, also of UCSF, said that clinical remission occurred in 41%, and endoscopic remission in 65%, in the same patient population. Both studies were presented at the Crohn’s and Colitis Congress.

“Older adults are one of the fastest growing subpopulations of IBD, and they’re very likely to be underincluded in clinical research trials, so we’re looking at the efficacy and safety of these drugs in older patients,” Garcia told MedPage Today.

MACE and thromboembolism were of particular interest, Garcia said, but there was only one thromboembolism, in an upadacitinib patient, and no MACE. The most common adverse event (AE) was mild infection, occurring in 23% of patients, with no difference between the drugs.

“They’re a population more likely to get infections, such as developing severe pneumonia, and that’s more threatening than in the younger population,” Zou said. But only two serious infections required hospitalization, one pyelonephritis case and one pneumonia case, both with upadacitinib.

Loss of therapies is a common problem with older adults, Zou suggested. “The problem with IBD is that it’s a lifetime disease, so most patients need several lines of medications,” he said. Often, patients run out of choices or cannot take certain therapies because they are contraindicated with other drugs they’re taking for comorbidities, he added. “The more options they have, the better.”

Nearly all the patients (95.4%) had previously taken an anti-TNF therapy, and most had taken an anti-integrin (63.3%). The patients had taken an average of 2.8 previous biologics, and 45.9% had previously taken an anti-IL-23/IL-12.

The 109 UCSF patients were 66% male with a mean age of 58.4. Also, 36.7% had Crohn’s disease and 63.3% had ulcerative colitis. All received JAK inhibitor monotherapy between January 2015-June 2024, with 45 patients taking tofacitinib and 64 taking upadacitinib.

The most common comorbidities among the patients were hyperlipidemia (40.4%) and hypertension (31.2%). A history of malignancy, (10.1%), diabetes (7.3%), and a history of cardiovascular disease (3.7%) were less common. None were current smokers, and 36.7% were former smokers.

Histologic remission occurred in 39% of participants, with no difference between tofacitinib and upadacitinib in clinical, endoscopic, or histologic remission rates or time to remission. Patients taking tofacitinib took 37.4 weeks to reach steroid-free remission compared to 12 weeks in those taking upadacitinib, but the difference was not significant (P=0.09).

Flares were more common among those taking tofacitinib (45.5%) than upadacitinib (14.3%, P=0.000), as was hospitalization for a flare (22.7% vs. 4.8%, P=0.013). Patients taking tofacitinib were also more likely to need IBD-related surgery at 17.8% versus 3.1%, respectively (P=0.015).

The most common infection was upper respiratory (10%) followed by skin infection (5%); four patients developed herpes zoster. Additional AEs included liver enzyme abnormalities (7%) and new skin cancers (2%). More patients discontinued tofacitinib (9%) than upadacitinib (0%) due to AEs (P=0.027).

Ayanna Lewis, MD, of Mount Sinai Morningside in New York City, said a lot of fear still exists regarding JAK inhibitors because of previous studies linking tofacitinib with MACEs.

“But we know that JAK inhibitors are effective therapies. They work quickly, and they treat disease effectively,” she told MedPage Today.

“Even in older patients, where we expect the immune system to be a little bit more suppressed, it seems like severe infections are still limited, and that’s important, because in terms of safety, that’s one of the things that we look at,” said Lewis, who was not involved in the study.

Noting the higher rate of herpes zoster in the tofacitinib group, Lewis added that “vaccination is still critical for this population,” including vaccination against pneumonia.

“My take-home point from all of this is that JAK inhibitors should be considered in patients who are over the age of 50, and that it’s important that these patients get vaccines early when you’re thinking about these therapies or thinking you might switch to these therapies,” Lewis said. “There is still a significant infection risk, even though it’s mild, but it can be prevented if vaccines are used.”

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