JAK Inhibitors: What Infections and Blood Clots to Watch For

When you’re managing a chronic autoimmune condition like rheumatoid arthritis or ulcerative colitis, finding a treatment that actually works can feel like a win. JAK inhibitors - drugs like tofacitinib, upadacitinib, and baricitinib - have delivered real relief for many people. They work fast, often better than older biologics, and come as pills instead of injections. But behind that convenience lies a serious trade-off: a higher risk of life-threatening infections and blood clots. If you’re considering or already taking one of these drugs, you need to know what to watch for - and what your doctor should be checking.

Why JAK Inhibitors Increase Infection Risk

JAK inhibitors block signaling pathways your immune system uses to fight off germs. That’s how they reduce inflammation in diseases like psoriasis or arthritis. But they don’t pick and choose which threats to block. They weaken your body’s ability to respond to viruses, bacteria, and fungi - even ones you’ve lived with for years.

The most common serious infection tied to these drugs is herpes zoster - better known as shingles. Even if you’ve had chickenpox as a kid or got the shingles vaccine, your risk still goes up. One study found 14.2% of all infection reports with JAK inhibitors involved shingles. Some patients get it within months of starting treatment. One Reddit user described being hospitalized for five days after developing shingles despite being vaccinated.

Other dangerous infections include tuberculosis (TB), fungal infections like histoplasmosis, and bacterial pneumonia. These aren’t rare outliers - they’re documented in clinical trials and real-world reports. The FDA and EMA both warn that these drugs can reactivate latent TB. That’s why doctors are supposed to test you for TB before you start treatment. If you’ve traveled to or lived in areas where TB is common, tell your doctor. Even if you’ve never had symptoms, you could still be carrying it.

Live vaccines are a hard no while you’re on these drugs. That means no MMR, chickenpox, nasal flu spray, or yellow fever shots. Inactivated vaccines like the flu shot or pneumococcal vaccine are still okay - but they might not work as well. Get them at least four weeks before starting a JAK inhibitor. Don’t wait until you’re already on the drug to catch up.

Thrombosis: The Silent Threat

While infections grab headlines, blood clots are just as dangerous - and often sneak up without warning. JAK inhibitors raise the risk of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). A 2022 analysis of over 126,000 patients showed JAK inhibitors increased the odds of blood clots by 2.37 times compared to other drugs. For pulmonary embolism? The risk jumped 2.81 times.

Why does this happen? It’s linked to how these drugs affect JAK2 - the same pathway that helps make platelets and regulate blood clotting. Inhibiting it doesn’t just calm inflammation; it throws off your body’s natural balance. The result? Clots can form in your legs, lungs, or even your brain.

Real stories show how sudden this can be. One patient on upadacitinib developed a clot in her calf after a long flight. Another, age 68, had a pulmonary embolism six months after starting treatment. Both had no prior history of clots. Age is a big factor: patients over 65 have nearly four times the risk. So do people with obesity (BMI over 30), a history of clots, or those on estrogen therapy. If you’ve had a clot before, JAK inhibitors are generally not recommended.

Not all JAK inhibitors are the same. Upadacitinib, which targets JAK1 more specifically, appears to carry a lower clot risk than tofacitinib, which hits multiple JAK pathways. In one trial, tofacitinib had nearly five times the VTE rate of upadacitinib in low-risk patients. But regulators still warn that all drugs in this class carry this risk - no exceptions.

Who Should Avoid JAK Inhibitors Altogether

The European Medicines Agency and FDA didn’t just slap on warnings - they changed who can get these drugs. As of 2022, JAK inhibitors are no longer first-line treatment for rheumatoid arthritis or other conditions. They’re now reserved for patients who haven’t responded to TNF inhibitors or other biologics.

You should not start a JAK inhibitor if you have:

• Any history of blood clots in your legs, lungs, or elsewhere
• Been diagnosed with cancer in the last five years (except non-melanoma skin cancer)
• Are 65 or older
• Smoke or used to smoke
• Have heart disease, high blood pressure, or high cholesterol
• Have a BMI over 30
• Are on estrogen-based therapy (like birth control or hormone replacement)

Even if you don’t have all these risk factors, your doctor should still run a full assessment. Many practices now use standardized checklists before prescribing. If your doctor skips this step, ask why. You’re not being difficult - you’re being smart.

Monitoring: What Your Doctor Should Be Checking

Starting a JAK inhibitor isn’t a one-time prescription. It’s an ongoing safety project. Your doctor should schedule regular tests:

• Complete blood count (CBC) every 4 to 8 weeks - to catch low white cells, red cells, or platelets
• Lipid panel at 4 and 12 weeks - JAK inhibitors raise LDL (“bad”) cholesterol by 10-15% and total cholesterol by up to 20%
• Annual cancer screenings - skin checks, colonoscopies, mammograms - because risk of some cancers increases
• Baseline D-dimer and leg ultrasound for high-risk patients - recommended by the American College of Chest Physicians

These aren’t optional. They’re part of the safety protocol. If your doctor isn’t ordering them, push back. You’re paying for more than a pill - you’re paying for vigilance.

What to Do If Something Feels Off

Don’t wait for a formal diagnosis. If you notice any of these signs, call your doctor immediately:

• Fever, chills, or night sweats - could signal infection
• Red, warm, swollen leg - possible deep vein thrombosis
• Sudden shortness of breath, chest pain, or rapid heartbeat - possible pulmonary embolism
• Painful rash or blisters on one side of your body - possible shingles
• Unexplained fatigue, dizziness, or pale skin - possible anemia or low platelets

If you’re diagnosed with a serious infection or blood clot, your doctor will stop the JAK inhibitor right away. That’s standard. But don’t assume you can restart it later. Once you’ve had one of these events, the risk of recurrence is high. Many patients switch to TNF inhibitors or other biologics after a clot or infection.

The Bigger Picture: Risk vs. Reward

Yes, JAK inhibitors work. Many patients say they’ve gone from being unable to hold a coffee cup to playing with their grandkids. But that benefit comes with real, measurable dangers. The ORAL Surveillance trial showed a 49% higher risk of death from any cause in patients on tofacitinib compared to TNF inhibitors. That’s not a small number.

It’s not about fear. It’s about awareness. If you’re young, healthy, and have tried everything else - and your doctor has ruled out all the risk factors - then JAK inhibitors can still be a good option. But if you’re over 60, have high blood pressure, or smoke, you need to ask: Is this the best choice? Or is there another path?

The market has already responded. In 2023, only 28% of new prescriptions for biologics were JAK inhibitors - down from 35% in 2020. More doctors are choosing TNF blockers first. That’s not because they’re less effective. It’s because they’re safer.

What’s Next?

Researchers are already working on next-generation drugs with better safety profiles. JAK1-selective inhibitors like upadacitinib and filgotinib show promise. Newer agents like TYK2 inhibitors are in trials and may offer similar benefits without the clot risk. But those aren’t widely available yet.

For now, the message is clear: JAK inhibitors aren’t dangerous for everyone. But they’re dangerous for enough people that you can’t treat them like a casual prescription. Know your risks. Ask the questions. Demand the tests. Your life depends on it.

Final Thoughts

JAK inhibitors aren’t the enemy. For many, they’re life-changing. But they’re not a magic bullet. They come with real, documented risks that demand attention - not avoidance, but awareness. If you’re on one, make sure you’re being monitored. If you’re thinking about starting one, make sure you’ve explored all other options. And never assume your doctor knows everything - ask the tough questions. Your health is worth it.