Skyrizi Side Effects and Safety for Crohn's Disease

Most pages about Skyrizi side effects reprint a generic bullet list, which makes it impossible to tell what the drug is doing and what Crohn's disease was already doing to you. The FDA prescribing information for Skyrizi (risankizumab-rzaa) reports its Crohn's trial side effects next to placebo rates, and side by side the picture is calmer than the list suggests (1). Many of us want that version: what beat placebo, why the blood draws run twelve weeks, and what the long-term data cannot promise.

Key Takeaways

• Skyrizi's FDA label carries no boxed warning; its Warnings and Precautions cover five topics: hypersensitivity, infections, tuberculosis, hepatotoxicity, immunizations (1)
• The most common Skyrizi side effects during IV induction were upper respiratory infections, 10.6 percent versus 9.3 percent on placebo, and headache, 6.6 versus 5.6 percent (1)
• Joint pain led maintenance reports but matched placebo exactly: 8.4 percent on 180 mg and 8.4 percent on placebo (1)
• Liver enzymes and bilirubin are checked at baseline and through induction to at least week 12, then per routine care (1)
• Extension data put serious infections at 2.9 events per 100 patient-years, near a register-based Crohn's estimate of 2.98 (4)
• The label says available data are insufficient to establish a drug-associated risk of birth defects or miscarriage (1)

What Skyrizi Is and Why Its Safety Profile Looks Different

Skyrizi (risankizumab-rzaa) is a selective interleukin-23 inhibitor approved for moderately to severely active Crohn's disease in adults. It blocks the p19 subunit found only on IL-23, one inflammatory messenger rather than a whole family. That narrow target is why its label reads differently from older classes: no boxed warning, and Warnings and Precautions limited to five topics (1).

Those five are hypersensitivity reactions, infections, tuberculosis, hepatotoxicity, and immunizations (1). A short list by biologic standards, and worth saying plainly what it does not mean. No boxed warning does not mean no risk; it means no single risk was judged serious enough for the label's strongest format. The precautions that remain are real, and most translate into something practical: a blood test, a screening, or a timing decision.

How IL-23 Blockade Differs From Anti-TNF and JAK Drugs

Anti-TNF drugs such as infliximab and adalimumab block tumor necrosis factor, used broadly in immune defense, and carry boxed warnings for serious infections and malignancy. JAK inhibitors such as upadacitinib act on a signaling hub shared by many pathways, and carry boxed warnings for infections, mortality, malignancy, cardiovascular events, and clots. If you have read about Rinvoq side effects, that is why the two conversations feel so different.

Skyrizi sits at the narrow end. Our guide to IL-23 inhibitors covers the mechanism, and the Skyrizi versus Stelara comparison explains how selective IL-23 blockade differs from also blocking IL-12.

The Most Common Skyrizi Side Effects, With Real Numbers

In the phase 3 Crohn's program, the overall rate of treatment-emergent adverse events was similar between Skyrizi and placebo groups (2)(3). That is the most useful fact here: much of what appears on a side effect list was also happening to people on no active drug.

During IV Induction

Induction is three intravenous infusions of 600 mg at weeks 0, 4, and 8. The label's induction table reports upper respiratory infections in 10.6 percent on Skyrizi versus 9.3 percent on placebo, headache in 6.6 versus 5.6 percent, and arthralgia, meaning joint pain, in 5 versus 4.4 percent (1).

Read those as pairs, not single numbers. Each sits only slightly above placebo, so the drug contributes something but ordinary life accounts for most of it. A head cold during induction is far more likely to be a head cold.

During Subcutaneous Maintenance

Maintenance moves to subcutaneous injections at home. The label's maintenance table lists arthralgia, abdominal pain, injection site reactions, anemia, pyrexia (fever), back pain, arthropathy, and urinary tract infection (1).

Two entries deserve attention. Arthralgia occurred in 8.4 percent on 180 mg, 9.2 percent on 360 mg, and 8.4 percent on placebo (1). The 180 mg rate is identical to placebo, and joint pain is already one of the most common symptoms of Crohn's itself. If your joints ache on Skyrizi, the trial data do not point at the drug.

Injection site reactions do look drug-related: 4.5 percent on 180 mg and 5.6 percent on 360 mg versus 2.8 percent on placebo (1). That is the tradeoff of a pen at home, usually redness or soreness rather than anything that stops treatment. In the 52-week FORTIFY maintenance trial, adverse event rates were similar across groups, and the most frequent events were worsening Crohn's disease, arthralgia, and headache (3).

Liver Enzymes: Why You Get Blood Draws During Induction

If your clinic has booked a string of blood tests over your first three months, this is why. Hepatotoxicity, meaning liver injury, is one of the five label precautions, and the monitoring schedule is written into the prescribing information (1).

What the Label Tells Your Doctor to Do

The label directs clinicians to evaluate liver enzymes and bilirubin at baseline and during induction at least up to 12 weeks of treatment, then follow routine patient management (1). Against the dosing schedule that makes sense: the three IV doses fall at weeks 0, 4, and 8, so a window reaching week 12 covers induction plus a margin. The draws are front-loaded, not open-ended.

The label also describes one case of serious drug-induced liver injury in a Crohn's patient. After two 600 mg intravenous doses, that patient's ALT rose to 54 times the upper limit of normal, AST to 30 times, and total bilirubin to 2.2 times (1). It resolved after corticosteroids and stopping the drug (1). One case in a program this size is rare, and it was caught and reversed, which is the argument for keeping the appointments.

Symptoms That Should Prompt a Call

Bloodwork usually catches liver trouble before anyone feels it, but symptoms are the backup. Worth reporting rather than waiting:

• New or unusual fatigue that does not fit your normal pattern
• Pain in the upper right side of your abdomen
• Dark urine
• Yellowing of the eyes or skin
• Nausea paired with loss of appetite

None of these automatically means liver injury, and in Crohn's most have ordinary explanations. They are the cluster that justifies a message to the clinic.

Infection Risk, Tuberculosis Screening, and Vaccines

Skyrizi dampens part of the immune system, so infection risk belongs in the conversation. The useful question is not whether risk exists but how large.

Serious Infection Rates Over the Long Term

Long-term open-label extension data put serious infections at 2.9 events per 100 patient-years, while a published register-based estimate for Crohn's disease generally sits at 2.98 (4). Close enough that this cohort's rate looked similar to Crohn's broadly. Different designs and populations, so it is a reassuring comparison rather than a controlled one.

What to Do Before Your First Dose

Two label requirements come first, both routine. The label says to evaluate patients for tuberculosis before starting, and not to give Skyrizi to anyone with active TB (1). In practice that is a skin or blood test, sometimes a chest X-ray. Latent TB is usually treatable first rather than a permanent barrier.

The label also says live vaccines should be avoided during treatment, and age-appropriate vaccinations completed before starting (1), so vaccine timing belongs in the weeks before induction. Our vaccine guide for Crohn's patients walks through the pre-biologic checklist, including which vaccines are live.

Long-Term Safety: What the Extension Data Show So Far

The SEQUENCE open-label extension followed 224 patients who had already failed anti-TNF therapy to week 100 of risankizumab treatment (4). The exposure-adjusted serious adverse event rate was 11.8 per 100 patient-years, serious infections accounted for 17 events at 2.9 per 100 patient-years, and no new safety signals were reported (4).

Efficacy held up alongside it. Clinical remission rates stayed stable through week 100, and more than 99 percent of those in remission at that visit were corticosteroid-free (4). If your worry is needing steroids again, that matters as much as the safety numbers.

The limits are real. These are interim results from an open-label, industry-funded extension, so there was no placebo group. Everyone enrolled had already responded to induction, making this a selected group the drug was working for, not a general population. Two years is a reasonable stretch, not a decade. Nothing worrying has surfaced in people doing well on it, which is good news and not a guarantee.

Pregnancy, Family Planning, and Putting the Risks in Context

This is where the evidence moves fastest, and where generic side effect pages are most out of date.

What the Evidence Does and Does Not Settle

The label is direct about the gap: available data are insufficient to establish a drug-associated risk of major birth defects or miscarriage, and a pregnancy exposure registry collects more (1). That is an absence of evidence, not evidence of safety or harm.

Two newer reports add texture. A US multicenter study of 444 women exposed to risankizumab before and during pregnancy reported fewer than 10 with adverse pregnancy outcomes and zero preterm births across subgroups; this paper has a published correction, so read the corrected version (5). A Danish report on two mother-infant pairs found limited placental transfer, a median cord blood to maternal ratio of 0.19, with the drug cleared by about 6 months (6). Two pairs is tiny, but low placental transfer is biologically meaningful.

The context often left out is that the comparison is not drug versus nothing. Untreated inflammation carries its own documented risks, so the real choice is controlled disease on a biologic versus active disease off one. That belongs with your gastroenterologist and obstetrician together.

Questions to Bring to Your Next Appointment

A short script helps when there is a lot to cover:

1. What baseline bloodwork do I need before my first dose, and when is it drawn?
2. When is my week 12 liver enzyme check, and what happens after it?
3. Has my tuberculosis screening been done, and do I need a chest X-ray?
4. Which vaccines should I complete before induction, and which live ones must I avoid?
5. If pregnancy is possible in the next year or two, how does that change the plan?
6. What symptoms should make me call rather than wait for my next visit?

None of this replaces the judgment of the team who knows your history. Any new symptom belongs in a message to them rather than a search bar, in week 2 of induction or year 3 of maintenance.

Frequently Asked Questions

What are the most common Skyrizi side effects in Crohn's disease?

During IV induction, the most reported were upper respiratory infections (10.6 percent versus 9.3 percent on placebo), headache (6.6 versus 5.6 percent), and joint pain (5 versus 4.4 percent) (1). In maintenance the label lists joint pain, abdominal pain, injection site reactions, anemia, fever, back pain, and urinary tract infection (1), most close to placebo.

Does Skyrizi have a boxed warning?

No. Skyrizi's FDA prescribing information carries no boxed warning, and its Warnings and Precautions cover five topics: hypersensitivity reactions, infections, tuberculosis, hepatotoxicity, and immunizations (1). Shorter than the anti-TNF or JAK inhibitor classes carry, though it does not mean the drug is risk-free.

Why do I need liver blood tests on Skyrizi?

The label directs clinicians to evaluate liver enzymes and bilirubin at baseline and during induction at least up to 12 weeks, then per routine management (1). The IV doses fall at weeks 0, 4, and 8, so the window covers induction plus a margin. The one label case of serious liver injury resolved after corticosteroids and stopping the drug (1).

Does Skyrizi raise infection risk a lot?

Open-label extension data reported serious infections at 2.9 events per 100 patient-years, close to a published register-based estimate of 2.98 for Crohn's disease generally (4). Tuberculosis screening is required before the first dose, and Skyrizi should not be given to anyone with active TB (1).

Can I get vaccines while taking Skyrizi?

Live vaccines should be avoided during Skyrizi treatment, and age-appropriate vaccinations completed before starting (1). Non-live vaccines are generally still an option, so sorting out timing before induction avoids delays.

Is Skyrizi safe during pregnancy?

The label says available data are insufficient to establish a drug-associated risk of major birth defects or miscarriage, and a pregnancy exposure registry is collecting more (1). A US study of 444 exposed women reported fewer than 10 with adverse pregnancy outcomes and zero preterm births across subgroups (5), and a small Danish report found limited placental transfer with clearance by about 6 months (6). Weigh it with your gastroenterologist and obstetrician.

How long is Skyrizi's safety record for Crohn's disease?

The SEQUENCE open-label extension followed 224 anti-TNF-experienced patients to week 100 with no new safety signals and a serious adverse event rate of 11.8 per 100 patient-years (4). Interim, open-label data in induction responders, so encouraging rather than conclusive.

References

1. AbbVie. SKYRIZI (risankizumab-rzaa) Prescribing Information. DailyMed, label version published July 31, 2026. Read label
2. D'Haens G, et al. Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. The Lancet, 2022;399:2015-2030. View on PubMed
3. Ferrante M, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the phase 3 FORTIFY maintenance trial. The Lancet, 2022;399:2031-2046. View on PubMed
4. Efficacy and safety of risankizumab in patients with moderately to severely active Crohn's disease: interim results from the SEQUENCE open-label extension study. Journal of Crohn's and Colitis, 2025;19:jjaf213. Read study
5. Pregnancy and Maternal Outcomes After Exposure to Risankizumab During Pregnancy: A Multi-Center Experience in the United States. Inflammatory Bowel Diseases, 2026;32:820-823 (see published correction). View on PubMed
6. Limited placental transfer and clearance of risankizumab by 6 months following in utero exposure. Journal of Crohn's and Colitis, 2026;20:jjag086. View on PubMed