Are Xeljanz and Rinvoq safe? Cutting through JAK inhibitor confusion
Messages on the safety of these disease-modifying drugs are mixed and confusing. Here’s what to know.
By Linda Rath | March 15, 2026
During the COVID pandemic, data suggested that people taking Janus kinase (JAK) inhibitors, like tofacitinib (Xeljanz, Xeljanz XR) or upadacitinib (Rinvoq), for rheumatoid arthritis (RA) were far more likely to be hospitalized or die from the coronavirus than those taking other arthritis drugs. Outcomes were even worse for patients taking JAK inhibitors — a type of targeted, disease-modifying drugs — who weren’t vaccinated.
At the same time, one JAK inhibitor — baricitinib (Olumiant) — was being given along with the common antiviral drug remdesivir to treat hospitalized COVID patients who needed help breathing. The drug combination reduced recovery time by only one day. But of those who got it, fewer had complications, including blood clots and serious infections — which are also potential side effects of JAK inhibitors.
The same mixed messages occur in other pandemic studies of JAK inhibitors. Most showed that patients taking them had worse — sometimes far worse — COVID outcomes than those using tumor necrosis factor (TNF) blocking biologic drugs, such as adalimumab (Humira).
In an effort to understand these discrepancies, researchers conducted a systematic review and meta-analysis of data from 12 trials involving nearly 13,000 hospitalized COVID patients treated with the JAK inhibitors baricitinib, tofacitinib or ruxolitinib (Jakafi). They found that those treated with a JAK inhibitor lived longer, were less likely to need a ventilator and had fewer serious complications than people who weren’t. The authors concluded that JAK inhibitors were a “safe and efficacious” treatment for COVID-19. The study was published in 2025 in The Lancet Respiratory Medicine.
The study findings led the FDA to issue a black box warning — the agency’s strongest — for all JAK inhibitors, including baricitinib and upadacitinib, citing an increased risk of blood clots, cancer and serious infections.
But other studies and experts have questioned that decision. For example, a group of international researchers, including one of the original investigators, re-examined the data and found that the chance of blood clots and serious infections was increased mainly in people age 65 and older who had a high risk of heart disease, high RA activity and a history of smoking. They concluded that JAK inhibitors are safe for most patients who don’t meet that description.
Furthermore, a study of more than 46,000 Swedish RA patients found that simply having high disease activity raised the risk of blood clots, even without considering JAK inhibitors.
Confusingly, yet another review and meta-analysis of 69 high-quality trials found that the rate of infections for people taking a JAK inhibitor was five times higher than in people taking placebo. The risk was even higher in patients taking a JAK inhibitor for dermatologic conditions, including psoriasis, eczema or hair loss.
Factors like age and co-existing medical conditions put certain people taking JAK inhibitors at higher risk. This includes people with rheumatoid arthritis aged 50 or older who are likely to have cardiovascular disease. Doctors should have frank discussions with patients about the drugs’ benefits and risks.
During the COVID pandemic, data suggested that people taking Janus kinase (JAK) inhibitors, like tofacitinib (Xeljanz, Xeljanz XR) or upadacitinib (Rinvoq), for rheumatoid arthritis (RA) were far more likely to be hospitalized or die from the coronavirus than those taking other arthritis drugs. Outcomes were even worse for patients taking JAK inhibitors — a type of targeted, disease-modifying drugs — who weren’t vaccinated.
At the same time, one JAK inhibitor — baricitinib (Olumiant) — was being given along with the common antiviral drug remdesivir to treat hospitalized COVID patients who needed help breathing. The drug combination reduced recovery time by only one day. But of those who got it, fewer had complications, including blood clots and serious infections — which are also potential side effects of JAK inhibitors.
The same mixed messages occur in other pandemic studies of JAK inhibitors. Most showed that patients taking them had worse — sometimes far worse — COVID outcomes than those using tumor necrosis factor (TNF) blocking biologic drugs, such as adalimumab (Humira).
In an effort to understand these discrepancies, researchers conducted a systematic review and meta-analysis of data from 12 trials involving nearly 13,000 hospitalized COVID patients treated with the JAK inhibitors baricitinib, tofacitinib or ruxolitinib (Jakafi). They found that those treated with a JAK inhibitor lived longer, were less likely to need a ventilator and had fewer serious complications than people who weren’t. The authors concluded that JAK inhibitors were a “safe and efficacious” treatment for COVID-19. The study was published in 2025 in The Lancet Respiratory Medicine.
The black box warning
In 2022, the results of a post-marketing study of the JAK inhibitor tofacitinib (conducted after the drug was FDA-approved and on the market) were published. This study compared the effects of tofacitinib to TNF blockers in RA patients age 50 and older who had at least one risk factor for cardiovascular disease. They found a rate of potentially fatal blood clots in the JAK inhibitor patients as well as more cancer and serious infections, including tuberculosis.The study findings led the FDA to issue a black box warning — the agency’s strongest — for all JAK inhibitors, including baricitinib and upadacitinib, citing an increased risk of blood clots, cancer and serious infections.
But other studies and experts have questioned that decision. For example, a group of international researchers, including one of the original investigators, re-examined the data and found that the chance of blood clots and serious infections was increased mainly in people age 65 and older who had a high risk of heart disease, high RA activity and a history of smoking. They concluded that JAK inhibitors are safe for most patients who don’t meet that description.
Furthermore, a study of more than 46,000 Swedish RA patients found that simply having high disease activity raised the risk of blood clots, even without considering JAK inhibitors.
Confusingly, yet another review and meta-analysis of 69 high-quality trials found that the rate of infections for people taking a JAK inhibitor was five times higher than in people taking placebo. The risk was even higher in patients taking a JAK inhibitor for dermatologic conditions, including psoriasis, eczema or hair loss.
Making sense of mixed messages
Many experts now say that it may have been a mistake to make policy based on a single trial. They also warn that JAK inhibitors shouldn’t be the first treatment for most autoimmune conditions due to safety concerns. (JAK inhibitors are rarely used as a first choice for conditions that don’t involve skin disease.)Factors like age and co-existing medical conditions put certain people taking JAK inhibitors at higher risk. This includes people with rheumatoid arthritis aged 50 or older who are likely to have cardiovascular disease. Doctors should have frank discussions with patients about the drugs’ benefits and risks.