JAK Inhibitors: What Infection and Blood Clot Risks to Watch For

When you're managing a chronic autoimmune condition like rheumatoid arthritis or psoriatic arthritis, finding a medication that actually works can feel like a win. But for many people starting a JAK inhibitor-drugs like tofacitinib, upadacitinib, or baricitinib-that win comes with a hidden cost. These drugs don't just calm inflammation. They also quiet down your immune system in ways that can leave you vulnerable to serious infections and dangerous blood clots. And unlike side effects you can easily spot, these risks often sneak up on you.

How JAK Inhibitors Work-and Why They Raise Risks

JAK inhibitors block specific signals inside your immune cells that trigger inflammation. That’s why they help with conditions like arthritis, eczema, and ulcerative colitis. But those same signals are also used by your body to fight off viruses and bacteria. When you shut them down, your defenses weaken. It’s not just about getting a cold. It’s about getting herpes zoster (shingles), pneumonia, or even tuberculosis you didn’t know you had.

The bigger concern? Blood clots. JAK inhibitors, especially those that block JAK2, interfere with how your bone marrow produces platelets and red blood cells. This doesn’t make you bleed more-it makes you more likely to clot. A 2022 study of over 126,000 patients found that people on these drugs had more than double the odds of developing a pulmonary embolism or deep vein thrombosis compared to those on other treatments. That’s not a small risk. It’s a life-threatening one.

The Infection Risks You Can’t Ignore

The most common infection linked to JAK inhibitors? Shingles. Even if you got the vaccine, it’s not foolproof. One patient on Reddit shared that they developed shingles three months after starting tofacitinib-despite being vaccinated. They ended up hospitalized for five days. That’s not rare. In fact, shingles accounts for nearly 15% of all infection reports tied to these drugs.

Other serious infections include:

• Lung infections like pneumonia and tuberculosis
• Herpes simplex outbreaks
• fungal infections like candidiasis
• Bacterial infections that spread quickly (sepsis)

The CDC and Infectious Diseases Society of America recommend you get all your vaccines-especially shingles, pneumococcal, and flu shots-at least four weeks before starting a JAK inhibitor. Once you’re on the drug, live vaccines (like MMR or varicella) are absolutely off-limits. You can’t afford to take chances.

And here’s something most people don’t realize: your risk doesn’t drop after a few months. These infections can show up anytime-even after a year or more on the medication. That’s why you need to stay alert. A fever, unusual fatigue, or a rash that won’t go away? Don’t wait. Call your doctor immediately.

When Blood Clots Strike: The Silent Threat

Venous thromboembolism (VTE) means blood clots forming in your veins. It can start as a swollen, painful calf (deep vein thrombosis) and turn into a clot traveling to your lungs (pulmonary embolism). Both can kill you.

The data is clear. A 2023 review of 62 studies showed that JAK inhibitors increased the risk of VTE by 2.3 times overall. But for patients over 65? The risk jumps to nearly four times higher. For those with a past history of clots? It’s more than five times higher.

Why does this happen? JAK2 inhibition messes with thrombopoietin, the hormone that tells your body how many platelets to make. Too little, and your blood doesn’t clot normally. Too much, and you get dangerous clots. It’s a delicate balance-and these drugs throw it off.

One patient on upadacitinib described a clot after a long flight. "My leg swelled up. I thought it was just sore from sitting. By the time I got to the ER, they confirmed it was a deep vein thrombosis. They stopped the drug right away."

Who Should Avoid JAK Inhibitors?

Not everyone is a candidate. Regulatory agencies like the FDA and EMA have strict rules now:

• Don’t start if you’re over 65
• Avoid if you smoke-or used to smoke
• Don’t use if you have heart disease, high blood pressure, or diabetes
• Never start if you’ve had a blood clot before
• Don’t use if you’re obese (BMI over 30)
• Don’t use if you’ve had cancer (especially lymphoma or lung cancer)

These aren’t suggestions. They’re hard limits. The FDA requires a black box warning-the strongest possible-for these risks. And the European Medicines Agency says JAK inhibitors should only be used if no other treatment works.

What Your Doctor Should Do Before Prescribing

A responsible doctor won’t just hand you a prescription. They’ll do a full risk check:

1. Review your medical history-especially for clots, heart issues, or infections
2. Order a baseline blood test: CBC (to check for low platelets), lipid panel (JAK inhibitors raise cholesterol), and D-dimer (a clotting marker)
3. Do a lower extremity ultrasound if you have swelling or risk factors
4. Confirm all vaccines are up to date
5. Discuss alternatives like TNF inhibitors, which have better safety data

Many practices now use standardized checklists. In 2020, only 32% of U.S. rheumatology clinics did. By 2023, that number jumped to 78%. That’s progress.

Monitoring After You Start

You can’t just take the pill and forget it. You need regular monitoring:

• Blood counts: 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%
• Infection signs: Fever, cough, night sweats, unexplained weight loss, skin sores
• Clot symptoms: Swelling, pain, warmth in one leg; sudden shortness of breath; chest pain

If you get a confirmed blood clot? The drug is stopped-permanently. If you get a serious infection? The drug is paused until you’re fully recovered.

Are Some JAK Inhibitors Safer Than Others?

Yes. Not all JAK inhibitors are created equal.

• Tofacitinib (Xeljanz): Pan-JAK inhibitor. Highest risk of clots and heart events. Linked to 73% higher pulmonary embolism risk in one major trial.
• Upadacitinib (Rinvoq): JAK1-selective. Newer data from the JAKARTA2 trial shows a lower VTE rate (0.2 per 100 patient-years) than tofacitinib (0.9).
• Baricitinib (Olumiant): JAK1/JAK2 inhibitor. Still carries clot risk, but some studies suggest slightly lower rates than tofacitinib.

The FDA and EMA now treat all JAK inhibitors as having the same risks-but emerging data suggests selectivity matters. JAK1-selective drugs may be safer for patients who need these medications.

What Patients Are Saying

Patient reviews on Drugs.com show a 6.2 out of 10 average rating. Why so low? Because 42% of negative reviews mention infections. Another 28% talk about blood clots.

One woman wrote: "I got shingles on my face. I thought it was a rash. By the time I saw my doctor, it had spread. I was on IV antivirals for a week. I wish I’d known the risks before I started." Another said: "I was on upadacitinib for six months. I flew across the country. My leg swelled. I thought it was tired muscles. It was a clot. I almost lost my leg." These aren’t outliers. They’re warnings.

The Bigger Picture

JAK inhibitors are powerful. They’ve helped thousands who didn’t respond to biologics. But their risks are real-and growing. The global market for these drugs slowed from 14% growth per year to under 9% after safety warnings. More doctors are choosing TNF inhibitors again because they’ve been used for over 20 years with known safety profiles.

The FDA and EMA are now requiring 10-year follow-up studies. That’s how seriously they’re taking this.

If you’re considering a JAK inhibitor, ask your doctor:

• "What’s my personal risk for infection and clotting?"
• "Have you checked my blood work and vaccination history?"
• "Are there safer alternatives?"
• "Will you monitor me closely? How often?"

Don’t assume it’s safe just because it’s prescribed. Your body isn’t a lab. It’s real. And these drugs carry real consequences.

What to Do If You’re Already on One

If you’re already taking a JAK inhibitor:

• Keep all your lab appointments
• Report any fever, swelling, or unusual fatigue right away
• Don’t skip the cholesterol test-it’s part of the safety picture
• Stay active. Move your legs during long flights or car rides
• Stay hydrated. Dehydration increases clot risk
• Don’t stop the drug without talking to your doctor

You might need this medication. But you also need to be smart about it.