TNF, JAK Inhibitors CV Safety Compared in PsA, AxSpA

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr Lianne Gensler

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

This article originally appeared on, part of the Medscape Professional Network.

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