Does Skyrizi weaken your immune system?
Short answer
Medication question
Skyrizi (risankizumab) modulates — rather than broadly weakens — the immune system. It selectively blocks IL-23, a cytokine that drives certain inflammatory responses. This targeted mechanism means it is more precise than older broad immunosuppressants, but it does increase risk of certain infections, particularly upper respiratory and urinary tract infections. Serious infections are rare but do occur.
This is a general research summary, not medical advice. A pharmacist can confirm it for your situation.
Key facts
Skyrizi (risankizumab) selectively blocks the p19 subunit of IL-23, not broad immune signaling pathways.
Most common infections with Skyrizi in trials: upper respiratory infections, UTIs, and tinea (fungal skin infections).
Skyrizi prescribing information requires TB testing and recommends hepatitis B screening before initiation.
Here's the nuance
A one-liner rarely tells the whole story. This is the honest detail behind the short answer above.
Skyrizi (risankizumab-rzaa) is a biologic medication that works by selectively inhibiting interleukin-23 (IL-23), a cytokine that plays a key role in driving the inflammatory cascades behind conditions like moderate-to-severe plaque psoriasis, psoriatic arthritis, and Crohn's disease. By specifically blocking the p19 subunit of IL-23, Skyrizi dampens the downstream IL-17 and Th17 inflammatory pathway — the one overactive in these conditions — without broadly suppressing all immune functions in the way older biologics or conventional immunosuppressants like corticosteroids or methotrexate do.
This mechanism is described as targeted immunomodulation rather than global immunosuppression. In clinical trials, Skyrizi's overall infection rates were generally comparable to placebo for most serious infections. The most commonly reported infections were upper respiratory tract infections (like the common cold and nasopharyngitis), urinary tract infections, and tinea (fungal skin infections). Serious infections — requiring hospitalization or intravenous antibiotics — occurred but were infrequent in trial data.
However, 'not broadly weakening the immune system' does not mean zero infection risk. Any biologic that modifies immune signaling carries some infection risk. Before starting Skyrizi, your prescriber will typically screen for tuberculosis (TB), hepatitis B, and other latent infections that could be reactivated. Skyrizi should not be used during an active infection. If you develop signs of infection while on Skyrizi — fever, chills, unusual cough, pain with urination — contact your prescriber promptly.
Live vaccines are generally not recommended while on Skyrizi or shortly after stopping it, because the immune response to live vaccines may be altered. Non-live (killed or mRNA) vaccines are generally fine and recommended to be up-to-date before starting Skyrizi. Your prescriber will guide you on vaccination timing specific to your situation.
This is not medical advice. The question of whether Skyrizi is appropriate, what monitoring you need, and how to handle any side effects should be managed with the prescriber who knows your full health history.
The key points
The handful of things that decide the answer — skim these if you only read one section.
Skyrizi targets IL-23 specifically, not the whole immune system
By blocking only the p19 subunit of IL-23, Skyrizi dampens the Th17/IL-17 inflammatory pathway relevant to psoriasis and Crohn's — without the broad immunosuppression of systemic corticosteroids or older biologics that inhibit multiple pathways.
Common infections are a known side effect
The most frequently reported infections in Skyrizi clinical trials were upper respiratory tract infections, urinary tract infections, and tinea. These occur at higher rates than with untreated conditions in some comparisons — report persistent or worsening infections to your prescriber.
Serious infections are rare but possible
Serious infections requiring hospitalization occurred infrequently in trials. Do not start Skyrizi if you have an active serious infection. Contact your prescriber if you develop signs of a serious infection (high fever, difficulty breathing, spreading redness or swelling) while on treatment.
TB and hepatitis B screening is required before starting
Skyrizi prescribing information requires TB testing before initiation and recommends hepatitis B screening. Latent infections can potentially reactivate during biologic therapy. Your prescriber will complete these evaluations as part of pre-treatment workup.
Live vaccines should be avoided while on Skyrizi
Because Skyrizi modifies immune signaling, live attenuated vaccines (e.g., MMR, varicella, yellow fever) are generally not recommended during treatment. Non-live vaccines are generally safe and encouraged. Get vaccinations up to date before starting Skyrizi when possible.
Please read before acting on this
General information — not medical advice
This page is a general research summary about the medication in question. It does not account for your specific health, other medicines you take, or your dose, and it can go out of date. It is not medical advice, a prescription, or a substitute for professional judgment.
Ask your pharmacist or prescriber before starting, stopping, changing, or continuing any medication — they can check it against your situation in minutes.
❓Frequently Asked Questions
Yes — non-live vaccines like the annual influenza shot, COVID-19 vaccine, pneumococcal vaccine, and Tdap are generally considered safe and are actually encouraged while on Skyrizi. Keeping vaccinations current before and during biologic therapy helps reduce overall infection risk. Live vaccines (such as MMR or varicella) are generally avoided while on Skyrizi. Discuss your vaccination schedule with your prescriber before and after starting treatment.
Compared to older biologics that inhibit broader targets (like TNF inhibitors, which affect a central immune mediator), IL-23 inhibitors like Skyrizi are considered more precisely targeted. In general, the infection risk profile of IL-23 inhibitors is considered favorable compared to TNF inhibitors. However, direct comparisons vary by study design and population. Your prescriber will weigh your specific risk factors — prior infections, comorbidities, other medications — when choosing among biologic options.
For mild infections like a cold or minor UTI, contact your prescriber for guidance on whether to continue Skyrizi or pause it temporarily. For serious infections — high fever, severe pain, spreading infection, difficulty breathing — seek medical care promptly and tell the treating clinician that you are on Skyrizi (a biologic). In general, Skyrizi should be withheld during active serious infections and restarted only after resolution, but this decision should be made by your prescriber.
Long-term safety data from Skyrizi clinical trials (extending to multiple years) has generally shown a stable safety profile without increasing infection rates over time. The IL-23 targeting mechanism has been associated with a generally favorable long-term safety record compared to broader immunosuppressants. As with any biologic, long-term use requires regular monitoring, including screening for any emerging infections and periodic assessment of your overall health status. Your prescriber will guide your monitoring plan.
A history of TB — even treated — requires careful evaluation before starting Skyrizi. All patients must be tested for latent TB before initiation. If latent TB is detected, treatment for latent TB must be completed (or at least started) before beginning Skyrizi, per prescribing guidelines. If you have a history of active or latent TB, discuss this fully with your prescriber — they will determine whether and when Skyrizi is appropriate for your situation.
Reviewed by
Dr. Chet TharpeMD
Last reviewed July 2026
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This content is for general informational purposes only. It is not medical advice, a prescription, or a substitute for professional judgment, and it does not account for your health, other medications, or dose. Always ask your pharmacist or prescriber before starting, stopping, or changing any medication.