JAK Inhibitors: What Infections and Blood Clots to Watch For

When you start a JAK inhibitor for rheumatoid arthritis, psoriasis, or another autoimmune condition, you’re not just getting relief from joint pain or skin flare-ups. You’re also stepping into a world where your body’s natural defenses are quietly turned down - and that comes with real, measurable risks. Two dangers stand out above all others: infections and blood clots. These aren’t rare side effects you read about in fine print. They’re serious, life-altering events that doctors now screen for, monitor closely, and sometimes prevent entirely - if you catch them early.

Why JAK Inhibitors Increase Infection Risk

JAK inhibitors work by blocking signals inside immune cells that tell the body to attack itself. That’s great for calming down inflammation. But those same signals also help your body fight off bacteria, viruses, and fungi. When you suppress them, your defenses get sluggish.

The most common serious infection linked to these drugs is herpes zoster - better known as shingles. Studies show about 1 in 7 people taking a JAK inhibitor develop shingles within the first year, even if they’ve had the vaccine. That’s more than double the rate seen in people on older biologics. The virus reactivates because your immune system can’t keep it in check anymore.

Other infections to watch for include tuberculosis (TB), pneumonia, and fungal infections like candidiasis. People on JAK inhibitors are more likely to get these infections, and they’re more likely to get them badly. One patient in Leeds reported being hospitalized after a mild cough turned into bacterial pneumonia within weeks of starting upadacitinib. Her doctor later said she’d likely had undiagnosed latent TB that flared up because the drug suppressed her immune response.

The FDA and EMA now require black box warnings for serious infections. That means your doctor should be asking you: Have you ever had TB? Have you traveled to areas where fungal infections are common? Are you up to date on vaccines? If not, they shouldn’t start you on a JAK inhibitor until those questions are answered.

Thrombosis: The Silent Threat

While infections are obvious, blood clots sneak up on you. Venous thromboembolism (VTE) - which includes deep vein thrombosis (DVT) and pulmonary embolism (PE) - is one of the most dangerous side effects of JAK inhibitors. And it’s not just a theoretical risk. Data from the ORAL Surveillance trial showed that patients on tofacitinib had more than double the risk of pulmonary embolism compared to those on TNF inhibitors.

Here’s what you need to know: JAK2 inhibition affects platelet production and blood clotting factors. That doesn’t mean your blood thickens - it means your body’s natural balance tips toward clotting. The risk isn’t the same for everyone. If you’re over 65, smoke, are overweight (BMI over 30), have a history of clots, or are on estrogen therapy, your risk jumps significantly. One 2023 analysis found that patients with prior VTE had more than five times the risk of another clot on a JAK inhibitor.

Real-world stories back this up. A Reddit user from Manchester described waking up with severe calf pain six months after starting upadacitinib. An ultrasound confirmed a deep vein thrombosis. Her rheumatologist stopped the drug immediately. She’s now on anticoagulants and switched to a different class of medication.

Even if you feel fine, you can still be developing a clot. Symptoms are often subtle: swelling in one leg, unexplained shortness of breath, chest pain that gets worse when you breathe. If you’re on a JAK inhibitor and notice any of these, don’t wait. Go to urgent care. Don’t assume it’s just muscle soreness or a bad flight.

Who Should Avoid JAK Inhibitors Altogether?

Not everyone is a candidate. Regulatory agencies have tightened restrictions because the risks aren’t evenly distributed. The European Medicines Agency (EMA) and FDA now say JAK inhibitors should only be used if:

• You’ve tried and failed other treatments like TNF inhibitors
• You’re under 65
• You don’t smoke
• You have no history of blood clots, heart attack, or stroke
• You don’t have active cancer or a recent cancer diagnosis
• Your BMI is below 30

If you check even one of these boxes, your doctor should be considering alternatives - like biologics, which carry lower clotting risk. In 2023, TNF inhibitors made up 42% of new prescriptions for rheumatoid arthritis, up from 35% in 2020, partly because of these safety concerns.

Even if you’re young and healthy, you’re not off the hook. A 2023 study in Arthritis Care & Research found that 1 in 5 patients who developed a clot on a JAK inhibitor had no known risk factors. That’s why screening isn’t optional - it’s standard.

What Your Doctor Should Check Before You Start

Before prescribing a JAK inhibitor, your rheumatologist should do more than just sign a form. They need to build a full picture of your health. Here’s what a responsible provider checks:

• History of blood clots - even if it was years ago
• Cardiovascular risk factors - high blood pressure, diabetes, high cholesterol
• Smoking status - current or past
• Age - risk increases sharply after 65
• Cancer history - including skin cancer
• Vaccination status - especially for shingles, pneumonia, and flu
• Baseline blood tests - CBC, lipid panel, D-dimer (in high-risk patients)

The American College of Rheumatology recommends a full lipid panel at 4 and 12 weeks after starting treatment. Why? Because JAK inhibitors raise cholesterol - sometimes by 15-20% within weeks. That’s not just a lab number. High LDL means higher heart disease risk, which compounds the clotting danger.

You should also get a TB test - even if you’ve been vaccinated. Latent TB can reactivate. A chest X-ray and interferon-gamma release assay (IGRA) are standard before starting.

Monitoring After You Start

Starting a JAK inhibitor isn’t a one-time decision. It’s an ongoing commitment to monitoring. Here’s what you’ll need to do:

• Every 4-8 weeks: Complete blood count to check for low white cells, red cells, or platelets
• At 4 and 12 weeks: Lipid panel to track cholesterol changes
• Every 3 months: Review for signs of infection - fever, cough, skin rashes, urinary symptoms
• Immediately if symptoms appear: Swelling, pain, or redness in one leg; sudden shortness of breath; chest pain

Some clinics now use digital alerts that flag patients who haven’t had a blood test in over 60 days. That’s not overkill - it’s safety.

If you develop a serious infection, your doctor will pause the JAK inhibitor until you’re fully recovered. If you get a blood clot, they’ll stop it permanently and switch you to another treatment. No exceptions.

The Bigger Picture: Are JAK Inhibitors Still Worth It?

It’s fair to ask: If the risks are this high, why use them at all?

Because for some people, they work better than anything else. In ulcerative colitis, JAK inhibitors can heal the colon lining when biologics fail. In alopecia areata, they can regrow hair in people who’ve lost it for years. In psoriatic arthritis, they reduce joint damage faster than older drugs.

The key is matching the drug to the person. A 40-year-old non-smoker with no history of clots and no other risk factors might have a very low chance of harm - and a high chance of life-changing improvement. A 70-year-old smoker with high blood pressure and a BMI of 35? The risk likely outweighs the benefit.

That’s why guidelines now treat JAK inhibitors like a scalpel - powerful, precise, but dangerous if used carelessly.

What’s Changing in 2026?

The field is evolving. Newer JAK inhibitors like upadacitinib and filgotinib are more selective - they target JAK1 more than JAK2. Early data suggests they may carry less clotting risk. The JAKARTA2 trial showed upadacitinib had less than half the VTE rate of tofacitinib in low-risk patients.

The European League Against Rheumatism is expected to release updated guidelines in early 2024 that may allow JAK1-selective drugs to be used more freely in certain patients. But until then, caution remains the rule.

The FDA and EMA are also requiring 10-year post-marketing studies to track long-term cancer and heart risks. That means we’ll know more in the next few years - but for now, we work with what we have.

Bottom Line: Know the Signs, Ask the Questions

JAK inhibitors aren’t dangerous for everyone. But they’re not safe for everyone either. If you’re considering one, make sure your doctor has done a full risk assessment - not just a checklist, but a real conversation about your life, your history, and your fears.

If you’re already on one, don’t ignore small symptoms. A sore throat that won’t go away? A swollen ankle? A sudden shortness of breath? These aren’t normal. Call your doctor. Don’t wait. Don’t assume it’s nothing.

You’re not just managing a disease. You’re managing your safety. And that means staying informed, staying vigilant, and speaking up - even when it feels uncomfortable.