How Skyrizi Causes Side Effects
Skyrizi (risankizumab-rzaa) is an IL-23 inhibitor used for plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. It suppresses immune responses targeting IL-23, which can lead to infections or other issues by dampening inflammation. Rare side effects—those occurring in less than 1% of patients in clinical trials—stem from this mechanism but appear infrequently.
Confirmed Rare Side Effects from Trials and Labeling
Clinical data and FDA labeling list these as rare:
- Anaphylaxis or severe allergic reactions, including angioedema and urticaria.[1]
- Serious infections like tuberculosis reactivation or fungal infections (e.g., histoplasmosis).[1][2]
- Malignancies, such as non-melanoma skin cancer or lymphoma, observed in <0.5% of patients.[1]
- Hepatic enzyme elevations leading to rare hepatitis cases.[2]
- Neutropenia or other blood disorders.[1]
Post-marketing reports add:
- Interstitial lung disease.[1]
- Vasculitis.[2]
Rates are low: in psoriasis trials (UltIMMa-1/2), serious adverse events hit 2-3%, with no single rare event exceeding 0.1%.[3]
How Often Do These Happen Compared to Common Ones?
Common side effects (1-10%) include upper respiratory infections and headaches. Rare ones like anaphylaxis occur in <0.1% across 5,000+ patients studied. Risk rises with comorbidities like immunosuppression history.[3][4] Long-term data (up to 5 years) shows no new rare signals beyond trials.[4]
Who Gets Rare Side Effects and Why?
Higher risk in patients with latent TB, recent live vaccines, or concurrent immunosuppressants. Screening for TB is required before starting. No pediatric data for rares; adult trials dominate.[1][2] Genetic factors aren't established, but IL-23 pathway variations may play a role.
What to Do if a Rare Side Effect Appears
Stop Skyrizi and seek emergency care for anaphylaxis or infection signs (fever, cough). Monitor liver enzymes quarterly. Report to FDA MedWatch. Most resolve after discontinuation.[1]
Are There Differences Across Indications?
Psoriasis trials report fewer hepatic rares than IBD (Crohn's: 1-2% elevated enzymes, rare progression to injury). No head-to-head data shows indication-specific rares.[3][4]
[1]: FDA Skyrizi Label
[2]: Skyrizi Prescribing Information
[3]: UltIMMa-1/2 Trial (NEJM)
[4]: 5-Year Safety Data (JAAD)