Yes, Xeljanz (tofacitinib) is an immunosuppressant. Its FDA-approved prescribing label states directly that it “can lower the ability of your immune system to fight infections.” Specifically, it belongs to a class of drugs called Janus kinase (JAK) inhibitors, which work by dialing down overactive immune signaling that drives inflammatory diseases like rheumatoid arthritis and ulcerative colitis.
How Xeljanz Suppresses the Immune System
Your immune cells communicate through chemical messengers called cytokines. When a cytokine docks onto a cell’s surface, enzymes called Janus kinases (JAKs) relay that signal inside the cell, telling it to ramp up inflammation or produce more immune cells. Xeljanz blocks three of these enzymes, JAK1, JAK3, and to a lesser degree JAK2, which interrupts the signaling chains of numerous cytokines involved in inflammation.
This is what makes the drug effective for autoimmune conditions: it quiets the misfiring immune response that attacks your own joints or gut lining. But the same mechanism also reduces your body’s ability to fight real threats like bacteria and viruses. That tradeoff is central to every decision around starting, monitoring, and continuing Xeljanz.
How It Differs From Biologic Immunosuppressants
Xeljanz is a small-molecule drug taken as a pill. That distinguishes it from biologic immunosuppressants like adalimumab or infliximab, which are large protein molecules delivered by injection or infusion. Biologics typically block one specific target, such as tumor necrosis factor (TNF). Xeljanz casts a wider net by blocking multiple JAK-dependent signaling pathways at once, which is partly why it carries a broader set of safety warnings.
In treatment guidelines, Xeljanz is generally reserved for patients who have already tried and either failed or could not tolerate a TNF blocker. It is not a first-line therapy for any of its approved conditions.
Conditions Xeljanz Is Approved to Treat
The FDA has approved Xeljanz for adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderately to severely active ulcerative colitis. In each case, approval is limited to patients who had an inadequate response or intolerance to at least one TNF blocker. For children aged two and older, it is approved for active psoriatic arthritis and a form of juvenile idiopathic arthritis, again after TNF blocker failure.
Infection Risks From Immune Suppression
Because Xeljanz dampens immune function, infections are the most common and most closely watched side effect. The most frequently reported serious infections include pneumonia, cellulitis, urinary tract infections, and shingles (herpes zoster). Shingles risk is notably elevated: it appeared in more than 5% of patients in clinical trials for ulcerative colitis and was listed among the most common adverse reactions overall. At higher doses, severe forms of shingles affecting the eyes, brain, or widespread skin were observed.
Upper respiratory tract infections and nasopharyngitis are also common. Because the drug suppresses the same pathways that keep dormant infections in check, tuberculosis reactivation is a specific concern. Patients are screened for both active and latent TB before starting therapy, and anyone with latent TB must complete treatment for it first.
FDA Boxed Warnings
Xeljanz carries the FDA’s most serious warning level, a Boxed Warning, covering four categories of risk: serious infections, cancer, blood clots, and death. A large post-marketing safety study found increased rates of major cardiovascular events, blood clots, and death at both approved doses compared to TNF blockers. The risks for cardiovascular events, clots, and death appeared to increase with dose.
Cancer risk was also higher. Lymphomas and lung cancers occurred more frequently in Xeljanz-treated patients than in those on TNF blockers. Current and former smokers faced an even greater risk of lung cancer and cancers overall. These findings prompted the FDA in 2021 to require updated warnings not just for Xeljanz but for the entire JAK inhibitor class.
Screening and Monitoring While on Xeljanz
Before starting Xeljanz, you can expect a round of baseline testing. This typically includes a complete blood count, TB evaluation, viral hepatitis screening, and liver function tests. The drug should not be started if your white blood cell counts are too low, specifically if lymphocytes are below 500 cells per cubic millimeter, neutrophils are below 1,000, or hemoglobin is below 9 g/dL. These thresholds exist because Xeljanz will push those numbers further down.
Vaccinations should be brought up to date before you begin treatment. Live vaccines, such as the live shingles vaccine, need to be given with appropriate spacing before starting the drug, since a suppressed immune system may not handle a live vaccine safely. Inactivated vaccines can generally still be given during treatment.
Why It’s Not Combined With Other Immunosuppressants
Xeljanz is not recommended alongside potent immunosuppressants like azathioprine or cyclosporine, or with biologic DMARDs. Combining these drugs stacks immunosuppressive effects, raising the risk of serious infection without established evidence of added benefit. Most patients in clinical trials who developed serious infections were already taking other immune-suppressing medications like methotrexate or corticosteroids alongside Xeljanz, which underscores how cumulative immune suppression amplifies danger.
If you’re taking Xeljanz and wondering about adding or switching medications, the layering of immunosuppressive effects is exactly what your prescriber will be evaluating.