JAK Inhibitors: What Infections and Blood Clots to Watch For

JAK Inhibitors: What Infections and Blood Clots to Watch For

JAK Inhibitor Risk Assessment Tool

Personalized Risk Assessment

This tool estimates your risk for serious infections and blood clots based on your medical history and current health factors. Results are based on FDA data and clinical studies.

Your Risk Factors

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When you’re managing a chronic autoimmune condition like rheumatoid arthritis or psoriatic arthritis, finding a treatment that actually works can feel like a win. JAK inhibitors-drugs like tofacitinib, upadacitinib, and baricitinib-deliver real results. Many patients see less joint pain, clearer skin, and improved mobility within weeks. But behind the benefits lies a quiet danger: serious infections and life-threatening blood clots. These aren’t rare side effects. They’re well-documented, FDA-mandated risks that demand your full attention before and during treatment.

Why JAK Inhibitors Raise Infection Risk

JAK inhibitors work by blocking signaling pathways that drive inflammation. That’s good for your joints and skin. But those same pathways help your immune system fight off viruses, bacteria, and fungi. When you shut them down, your body’s defenses weaken. It’s not just about catching a cold. The real concern is serious infections-ones that land you in the hospital.

Herpes zoster (shingles) is the most common serious infection linked to these drugs. Even if you’ve had the vaccine, the risk doesn’t disappear. A 2022 analysis of over 15,000 adverse event reports found that 14.2% of all infection cases tied to JAK inhibitors were shingles. Some patients develop it within three months of starting treatment. One Reddit user, 'ArthritisWarrior87,' described being hospitalized for five days after developing shingles despite being vaccinated. That’s not an outlier-it’s a pattern.

Other infections to watch for include tuberculosis (TB), pneumonia, and fungal infections like candidiasis. People with a history of TB, diabetes, or recent organ transplants are at higher risk. The CDC and Infectious Diseases Society of America (IDSA) recommend testing for latent TB and getting all recommended vaccines-including pneumococcal, flu, and hepatitis B-at least four weeks before starting a JAK inhibitor. Live vaccines (like MMR or varicella) are strictly off-limits once you’re on treatment.

The Blood Clot Danger: More Than Just a Statistic

If infections are the loud warning, blood clots are the silent one. Venous thromboembolism (VTE)-which includes deep vein thrombosis (DVT) and pulmonary embolism (PE)-has become the biggest safety red flag for JAK inhibitors. In 2021, the FDA added a black box warning after the ORAL Surveillance trial showed a 73% higher risk of pulmonary embolism in patients taking tofacitinib compared to TNF inhibitors.

The numbers aren’t abstract. A 2023 review of 62 studies found that JAK inhibitors more than doubled the risk of VTE overall. For patients over 65, the risk jumped nearly fourfold. For those with a prior clot history, it was over five times higher. One patient on upadacitinib described a DVT in her calf after a long flight. Her rheumatologist stopped the drug immediately. She didn’t need a complication to realize the stakes.

Why does this happen? JAK2 inhibition interferes with platelet production and blood vessel function. Studies show these drugs can reduce thrombopoietin signaling, which affects how your body makes platelets. At the same time, they suppress anti-inflammatory signals that normally protect blood vessels. The result? A perfect storm for clotting.

Not All JAK Inhibitors Are the Same

You might assume all JAK inhibitors carry the same risk. They don’t. Their chemical profiles vary, and so do their safety signals.

- Tofacitinib (Xeljanz): Affects JAK1 and JAK3 most, with some JAK2 activity. Highest VTE risk in trials. Requires twice-daily dosing. Linked to the most black box warning data.

- Upadacitinib (Rinvoq): Highly JAK1-selective. Newer data from the JAKARTA2 trial (ACR 2023) showed only 0.2 VTE events per 100 patient-years in low-risk patients-much lower than tofacitinib’s 0.9.

- Baricitinib (Olumiant): Blocks JAK1 and JAK2. Similar risk profile to tofacitinib, especially in older adults.

- Filgotinib (Jyseleca): JAK1-selective with minimal JAK2 impact. Not approved in the U.S., but European data suggests a potentially better safety profile for clotting.

This matters. If you’re over 65, have a history of clots, or smoke, your doctor should consider a JAK1-selective option like upadacitinib over tofacitinib. It’s not just about efficacy-it’s about minimizing risk.

Patient clutching leg as glowing blood clot threads rise toward heart in hospital room under emergency lights.

Who Should Avoid JAK Inhibitors Altogether?

The European Medicines Agency (EMA) and FDA don’t just warn-they restrict. As of 2022, JAK inhibitors are no longer first-line options. They’re reserved for patients who haven’t responded to other treatments like TNF inhibitors-and only if they don’t have certain risk factors.

You should not start a JAK inhibitor if you have:

  • A history of deep vein thrombosis or pulmonary embolism
  • Active or untreated tuberculosis
  • Current or recent cancer (excluding non-melanoma skin cancer)
  • Age 65 or older with cardiovascular risk factors
  • Obesity (BMI ≥30)
  • Smoking history
  • Use of estrogen-containing birth control or hormone therapy
The American College of Rheumatology (ACR) 2023 guidelines are clear: If you have two or more of these risk factors, JAK inhibitors are not the right choice. There are safer alternatives-biologics, other DMARDs-that won’t put you at higher risk for a clot or fatal infection.

What Monitoring Is Required?

Starting a JAK inhibitor isn’t a one-time prescription. It’s the start of ongoing vigilance.

Your doctor should order:

  • Complete blood count (CBC) every 4-8 weeks to check for low white blood cells, platelets, or anemia
  • Lipid panel at 4 and 12 weeks-JAK inhibitors raise cholesterol by 15-20% within months
  • Baseline D-dimer and lower extremity ultrasound for high-risk patients (per ACCP 2023 guidelines)
  • Regular infection screening: annual TB testing, prompt evaluation of fever or unusual fatigue
If you develop sudden leg swelling, chest pain, shortness of breath, or unexplained fever, stop the drug and contact your doctor immediately. Don’t wait. Don’t assume it’s “just a cold.”

Split image: healthy young person vs. frail patient surrounded by infection and clot icons, with JAK pill and biologic syringe on scale.

What Patients Are Saying

Patient reviews on Drugs.com give JAK inhibitors a 6.2 out of 10. Why? Because the efficacy is real-but the fear is real too. In a 2023 Arthritis Foundation survey of 1,200 users:

  • 68% worried about infections
  • 57% feared blood clots
  • 82% said they felt better when no complications occurred
One user wrote: “I got my life back on tofacitinib-but lost it again when I got shingles. Now I’m on a biologic. Worth the extra shot.”

These aren’t just opinions. They’re lived experiences that mirror the data.

The Bigger Picture: Where Do JAK Inhibitors Stand Today?

Since the 2021 FDA safety alert, JAK inhibitor prescriptions have dropped from 35% to 28% of new biologic or targeted DMARD starts in rheumatoid arthritis. TNF inhibitors are making a comeback. Why? Because their safety profile is better understood. They don’t carry the same clotting or infection risks.

Newer drugs like TYK2 inhibitors (e.g., deucravacitinib) are entering the market with early data suggesting lower infection and clotting rates. They may become the preferred next step for patients who need more than a traditional biologic but can’t tolerate JAK inhibitors.

The takeaway? JAK inhibitors aren’t going away. But they’re no longer the go-to option. They’re a targeted tool-for specific patients, under strict monitoring, with full awareness of the stakes.

Final Checklist Before Starting

Before you agree to a JAK inhibitor, make sure your doctor checks these boxes:

  1. Have you been screened for TB and hepatitis B?
  2. Have you received all non-live vaccines (flu, pneumonia, shingles) at least 4 weeks ago?
  3. Do you have a history of blood clots, cancer, or heart disease?
  4. Are you over 65? Do you smoke? Is your BMI over 30?
  5. Have you discussed alternatives like TNF inhibitors or IL-17 blockers?
  6. Will you get blood tests every 4-8 weeks? Will your doctor know what to do if you get sick?
If any answer is “no,” push back. Your health isn’t a trade-off between convenience and safety. It’s about choosing the right tool for your body-and knowing when to walk away.

Can JAK inhibitors cause shingles even if I got the vaccine?

Yes. The shingles vaccine reduces risk but doesn’t eliminate it, especially with JAK inhibitors. These drugs suppress immune responses enough that even vaccinated patients can develop shingles. Cases have been reported within weeks to months of starting treatment. If you notice a painful rash, especially on one side of your body, contact your doctor immediately.

How soon after starting a JAK inhibitor do blood clots usually occur?

Most cases happen within the first 6 to 12 months, but they can occur at any time. The highest risk is during periods of immobility-like long flights, hospital stays, or recovery from surgery. One patient developed a deep vein thrombosis after a 10-hour flight while on upadacitinib. Don’t assume it’s safe just because you’ve been on the drug for a year.

Are JAK inhibitors safe for younger patients without risk factors?

For younger patients (under 50) with no history of clots, cancer, or smoking, the risk is lower-but not zero. Studies still show a 2-3 times higher chance of VTE compared to placebo. JAK1-selective drugs like upadacitinib appear safer in this group. Still, alternatives like TNF inhibitors are often preferred unless the patient hasn’t responded to them.

Do JAK inhibitors raise cholesterol, and is that dangerous?

Yes. Within 4 weeks, most patients see a 15-20% rise in total cholesterol and a 10-15% increase in LDL (bad cholesterol). HDL (good cholesterol) also rises slightly, but not enough to offset the risk. This isn’t just a lab number-it increases long-term heart disease risk. Your doctor should check your lipid panel at 4 and 12 weeks and may start a statin if levels stay high.

What happens if I get a serious infection while on a JAK inhibitor?

You must stop the drug immediately. Continuing it while infected can turn a treatable illness into a life-threatening one. The American College of Rheumatology recommends holding the medication until the infection clears completely. Once you’re recovered, your doctor may restart it-but only after reassessing whether the benefits still outweigh the risks.

11 Comments

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    waneta rozwan

    January 16, 2026 AT 22:53

    So let me get this straight-you’re telling me I can trade my joint pain for a 73% higher chance of a blood clot that could kill me? And they call this medicine? I’m not even mad, I’m just impressed by how well Big Pharma sells fear as a cure. 🤡

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    Nicholas Gabriel

    January 17, 2026 AT 04:19

    Okay, let’s pause for a second-this is one of the most responsibly written pieces on JAK inhibitors I’ve ever seen. Seriously. The breakdown of risk by drug? The monitoring checklist? The emphasis on vaccination timing? This isn’t just info-it’s a survival guide. If your doctor hasn’t walked you through this, find a new one. Period.

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    Cheryl Griffith

    January 17, 2026 AT 12:06

    I started baricitinib last year. Had shingles three months in-even though I got the shot. Wasn’t fun. Hospital stay. Pain that felt like fire under my skin. But here’s the thing: I’m still on it, because my knees can finally bend without screaming. I just do my bloodwork religiously, avoid long flights, and keep my doctor on speed dial. It’s not perfect. But it’s mine.

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    swarnima singh

    January 17, 2026 AT 20:21

    u r all so obsessed with science but no one talks about the soul... the body is just a vessel... when u suppress inflammation u suppress the spirit too... i lost my cousin to this drug... he was just trying to walk again... now he’s just a ghost in a hospital bed... 🌑

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    Isabella Reid

    January 17, 2026 AT 21:26

    My mom’s on upadacitinib. She’s 58, no clots, never smoked, BMI 24. Her RA was wrecking her life-couldn’t hold her grandkids. Now she bakes cookies again. Yes, she gets labs every 6 weeks. Yes, she avoids long plane rides. But she’s alive, present, and happy. Sometimes the risk is worth it if you’ve already lost your quality of life.

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    Jody Fahrenkrug

    January 19, 2026 AT 03:01

    Just wanted to say thanks for this. I’m 32, had a DVT last year, and my rheum just pulled me off tofacitinib. I was scared to ask if I could ever try again. Now I know-maybe upadacitinib? But only if I’m extra careful. This helped me feel less alone.

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    Kasey Summerer

    January 20, 2026 AT 15:04

    So JAK inhibitors = autoimmune superhero... but also blood clot villain? 🤦‍♂️ Cool. So we’re just trading one chronic condition for another? Next thing you know, we’ll be taking a pill to fix the side effects of the pill we took to fix the first pill. Welcome to 2025, folks. 💊💀

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    Corey Chrisinger

    January 21, 2026 AT 05:33

    It’s funny how we treat medicine like a menu. ‘I’ll have the JAK inhibitor with a side of monitoring and a glass of anxiety.’ But the truth? We’re all just trying to survive another day without pain. The data is scary, yes-but so is being trapped in your own body. Maybe the real question isn’t ‘Is it safe?’ but ‘What’s safer: this, or not living at all?’

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    Travis Craw

    January 23, 2026 AT 00:55

    my doc said i could try upadacitinib but i dont know... i saw that vid of that guy with the clot and it freaked me out... i just want to walk to my mailbox without crying

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    Christina Bilotti

    January 24, 2026 AT 09:39

    Wow. A post that actually cites studies, differentiates between JAK inhibitors, and doesn’t just say ‘talk to your doctor.’ How novel. I assume the author is either a rheumatologist or someone who read a single NEJM article and decided to be the hero of Reddit. Either way-respect. Most of you are still arguing about whether ‘natural remedies’ cure RA. Sigh.

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    waneta rozwan

    January 25, 2026 AT 20:29

    Wait, so if I’m over 65, obese, and smoke, I’m just supposed to give up on feeling good? That’s not medicine. That’s surrender. I’m not dying because I wanted to walk again. I’m dying because the system decided I’m not worth the risk. I’m taking my chances.

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