JAK Inhibitors: What You Need to Know About Infection and Blood Clot Risks
Dec, 15 2025
JAK Inhibitor Risk Assessment Tool
This tool helps you understand your risk of infections and blood clots while taking JAK inhibitors. Based on your answers, it calculates a risk score and provides personalized recommendations. Remember: this tool is for informational purposes only and should not replace professional medical advice.
Blood Clot Risk Assessment
Infection Risk Assessment
What Are JAK Inhibitors and Why Are They Used?
JAK inhibitors are a type of oral medication designed to block specific enzymes in the body called Janus kinases. These enzymes play a key role in the immune systemâs inflammatory response. By slowing down this overactive signaling, JAK inhibitors help reduce swelling, joint pain, and skin inflammation in conditions like rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and atopic dermatitis. Theyâre often prescribed when other treatments - like methotrexate or TNF inhibitors - havenât worked well enough. Common brands include tofacitinib (Xeljanz), upadacitinib (Rinvoq), and baricitinib (Olumiant). While they work quickly and effectively for many people, they come with serious safety warnings that canât be ignored.
Why Infection Risk Is a Major Concern
One of the biggest dangers with JAK inhibitors is how they weaken your bodyâs ability to fight off infections. Because these drugs dampen immune signaling, youâre more vulnerable to bacterial, viral, and fungal infections. The most commonly reported serious infection is herpes zoster - also known as shingles. Studies show about 1 in 7 people taking JAK inhibitors develop shingles, even if theyâve been vaccinated. One patient on Reddit shared that despite getting the shingles vaccine, they ended up hospitalized for five days after starting tofacitinib.
Beyond shingles, thereâs a higher risk of tuberculosis (TB), pneumonia, and even rare but deadly fungal infections like invasive aspergillosis. The FDA and EMA both require doctors to screen for latent TB before starting treatment. If youâve ever had TB, lived in a country where itâs common, or been in close contact with someone who had it, your doctor should test you first.
Doctors also recommend getting all necessary vaccines - including flu, pneumococcal, and hepatitis B - at least four weeks before starting a JAK inhibitor. Once youâre on the drug, live vaccines (like MMR or chickenpox) are completely off-limits. If you develop a fever, cough that wonât go away, or unexplained fatigue, donât wait. Call your doctor immediately. Early treatment can prevent a minor infection from becoming life-threatening.
Thrombosis: The Hidden Blood Clot Risk
Another serious side effect tied to JAK inhibitors is venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). These are blood clots that form in the legs or lungs and can be fatal if not caught quickly. The FDA added a black box warning for this risk in September 2021 after a large study showed patients on tofacitinib had more than double the risk of pulmonary embolism compared to those on TNF inhibitors.
The risk isnât the same for everyone. People over 65, those who smoke, have obesity (BMI over 30), or have had a previous blood clot are at the highest risk. One patient on upadacitinib described developing a DVT in their calf after a long flight - something their rheumatologist immediately linked to the medication. Blood clots can happen even without obvious triggers like travel or surgery.
Research shows JAK2 inhibition - which affects platelet production and blood cell signaling - is likely behind this increased clotting risk. While newer JAK inhibitors like upadacitinib (which targets JAK1 more specifically) may carry lower risk, the evidence isnât conclusive yet. The European Medicines Agency now says all JAK inhibitors, regardless of brand, carry this warning.
Who Should Avoid JAK Inhibitors?
Not everyone is a candidate for these drugs. Regulatory agencies like the FDA and EMA have made it clear: JAK inhibitors should only be used when other treatments have failed - and only if you donât have certain risk factors. You should avoid them if you:
- Are 65 years or older
- Are a current or former smoker
- Have a history of blood clots, heart attack, or stroke
- Have uncontrolled high blood pressure or high cholesterol
- Have a personal or family history of cancer
- Have active infections
Even if youâre young and healthy, your doctor should still run a full risk assessment. This includes checking your lipid levels, blood counts, and possibly doing a D-dimer test or leg ultrasound if youâre at high risk for clots. In Australia, the TGA requires doctors to document these risk factors before prescribing. If your doctor doesnât ask about your smoking history or recent travel, itâs time to ask why.
Monitoring and What to Watch For
Once you start a JAK inhibitor, you canât just take it and forget it. Regular monitoring is non-negotiable. Most guidelines recommend:
- Complete blood count every 4 to 8 weeks to check for low white blood cells, red blood cells, or platelets
- Lipid panel at 4 weeks and again at 12 weeks - cholesterol often rises by 15-20% within the first month
- Annual skin checks for signs of skin cancer
- Immediate blood tests if you feel short of breath, have chest pain, or notice swelling in one leg
If you develop a fever, swollen leg, or sudden trouble breathing, stop the medication and get emergency care. These arenât side effects to wait out - theyâre red flags. Many rheumatology clinics now use standardized checklists to track these risks, and over 75% of U.S. practices have adopted them since 2022.
How Do JAK Inhibitors Compare to Other Treatments?
Itâs easy to assume all biologics are equally safe, but thatâs not true. TNF inhibitors - like adalimumab (Humira) or etanercept (Enbrel) - have been used for over 20 years with a well-understood safety profile. While they also increase infection risk, they donât carry the same blood clot or heart attack warnings as JAK inhibitors.
Studies show that for rheumatoid arthritis patients without major risk factors, TNF inhibitors and JAK inhibitors work about the same in reducing pain and joint damage. But when it comes to safety, TNF inhibitors win. The ORAL Surveillance trial found patients on tofacitinib had a 33% higher risk of major heart events and a 54% higher risk of cancer (excluding skin cancer) compared to those on TNF inhibitors.
Thatâs why most guidelines now recommend TNF inhibitors as first-line biologics, with JAK inhibitors reserved for cases where biologics donât work or arenât tolerated. For patients with high clotting risk, newer options like TYK2 inhibitors (still in trials) may become preferred in the future.
Real Patient Experiences
Behind the statistics are real people. On patient forums like Reddit and Drugs.com, common themes emerge:
- "I felt amazing on upadacitinib - until I got a blood clot."
- "I had shingles twice in one year after starting tofacitinib. My doctor said it was rare - but it happened to me."
- "I stopped the drug after my cholesterol jumped to 280. My doctor said it was normal, but I couldnât live with that risk."
These arenât outliers. A 2023 Arthritis Foundation survey found that 68% of patients worried about infections and 57% feared blood clots. Yet, 82% of those who stayed on the medication reported good symptom control - as long as no complications occurred.
Thatâs the tightrope: managing a chronic disease without trading one health crisis for another. The decision isnât just about which drug works best - itâs about which risks youâre willing to take.
Whatâs Next for JAK Inhibitors?
Regulators and researchers are still learning. The FDA has mandated a 10-year follow-up study on all JAK inhibitors to track long-term cancer and heart risks. The EULAR registry is tracking 10,000 patients across Europe specifically for blood clots. Early data from the JAKARTA2 trial suggests upadacitinib may have a lower clot risk than tofacitinib - but only in patients without traditional risk factors.
As newer, more selective drugs emerge - especially those targeting JAK1 instead of JAK2 - the hope is that efficacy remains high while risks drop. But for now, the message is clear: JAK inhibitors are powerful tools, but theyâre not first-line. Theyâre second-line, third-line, or even last-resort options - depending on your health history.
Final Thoughts: Is It Worth It?
Thereâs no one-size-fits-all answer. If youâre in severe pain, unable to work, or losing mobility, the benefits of JAK inhibitors can be life-changing. But if youâre over 65, smoke, have high cholesterol, or have had a clot before, the risks may outweigh the rewards.
The key is not to avoid these drugs entirely - but to approach them with eyes wide open. Ask your doctor: "Whatâs my specific risk for infection or blood clots?" "Have you checked my lipid levels and blood counts?" "Are there alternatives I havenât tried?" If they canât answer clearly, get a second opinion.
These medications arenât dangerous because theyâre flawed - theyâre dangerous because theyâre powerful. And with great power comes great responsibility - for both patient and provider.
Can JAK inhibitors cause shingles even after vaccination?
Yes. While the shingles vaccine reduces the risk, it doesnât eliminate it. JAK inhibitors suppress immune responses enough that even vaccinated people can develop shingles. Studies show about 14% of patients on JAK inhibitors who were vaccinated still got shingles. If youâre on one of these drugs, watch for tingling, burning, or a painful rash - especially on one side of your body - and contact your doctor right away.
How soon after starting a JAK inhibitor do blood clots occur?
Blood clots can happen anytime, but most cases occur within the first 6 to 12 months of treatment. However, there are documented cases even after 2 years. The risk doesnât disappear over time. Thatâs why ongoing monitoring is required - not just at the start. If youâre on a JAK inhibitor and take a long flight, have surgery, or become immobile for any reason, your risk spikes. Talk to your doctor about preventive measures if youâre in one of these situations.
Are newer JAK inhibitors safer than older ones?
Possibly. Upadacitinib and filgotinib are more selective for JAK1, which may reduce the impact on blood cell production and clotting pathways. Early data from clinical trials suggest lower rates of blood clots compared to tofacitinib, which blocks multiple JAK enzymes. But these drugs havenât been used long enough to confirm this safety advantage. Regulatory agencies still treat all JAK inhibitors as having similar risks until more long-term data is available.
Do JAK inhibitors increase the risk of cancer?
Yes. The ORAL Surveillance trial found a 54% higher risk of cancer (excluding non-melanoma skin cancer) in patients taking tofacitinib compared to TNF inhibitors. This includes lymphoma, lung cancer, and other solid tumors. The risk appears higher in older patients and those with a history of smoking or prior cancer. Regular skin checks and age-appropriate cancer screenings are essential for anyone on long-term JAK inhibitor therapy.
What should I do if I miss a dose of my JAK inhibitor?
If you miss a dose, take it as soon as you remember - unless itâs close to your next scheduled dose. Donât double up. Missing doses doesnât immediately increase infection or clot risk, but inconsistent use can reduce effectiveness and make your condition harder to control. If you miss more than two doses in a row, contact your doctor. They may want to check your inflammation levels before restarting.
Next Steps for Patients
If youâre considering a JAK inhibitor, make sure youâve tried at least one other biologic or DMARD first. If youâre already on one, ask your doctor for a copy of your last blood work and lipid panel. If you donât have one from the past 3 months, schedule a test. Review your vaccination status - especially for shingles, pneumonia, and flu. If youâre over 50 and havenât had the shingles vaccine, ask about getting it - but only before starting the medication.
If youâre worried about blood clots, avoid long periods of sitting, stay hydrated, and move regularly. If you smoke, quit. If youâre overweight, talk to your doctor about a safe weight loss plan. These arenât just lifestyle tips - theyâre risk-reduction strategies.
JAK inhibitors can change lives. But they also demand careful management. Donât let convenience or desperation override safety. The best outcomes come from informed decisions - not rushed ones.
Tiffany Machelski
December 16, 2025 AT 06:27SHAMSHEER SHAIKH
December 17, 2025 AT 13:55James Rayner
December 17, 2025 AT 22:20the pain of arthritis vs. the fear of blood clots vs. the guilt of saying 'no' to something that works...
it's not just medicine, it's a moral calculus we do every day. đ¤đ
Souhardya Paul
December 18, 2025 AT 16:37Josias Ariel Mahlangu
December 18, 2025 AT 20:39anthony epps
December 19, 2025 AT 15:52Andrew Sychev
December 20, 2025 AT 09:28Dan Padgett
December 21, 2025 AT 23:29Hadi Santoso
December 23, 2025 AT 19:01Arun ana
December 25, 2025 AT 05:37Kayleigh Campbell
December 26, 2025 AT 22:40Dave Alponvyr
December 26, 2025 AT 23:29Kim Hines
December 27, 2025 AT 00:58Cassandra Collins
December 28, 2025 AT 11:12