Most common Skyrizi side effects are mild and resolve within days to a couple of weeks. The drug itself has a half-life of about 28 days, meaning it takes roughly five to six months after your last dose for it to fully clear your system. That timeline matters because some effects can linger as long as the drug remains active in your body.
The FDA prescribing information doesn’t list exact durations for most side effects, so the best picture comes from combining clinical trial data, pharmacokinetic information, and real-world guidance from dermatology organizations.
Injection Site Reactions: 3 to 5 Days
Injection site reactions are the side effect with the clearest timeline. Redness, swelling, itching, bruising, or a small rash at the injection site typically clears up within 3 to 5 days, according to the British Association of Dermatologists. These reactions are usually mild. If the redness, pain, or swelling around the injection site gets worse instead of better after that window, that’s worth a call to your prescriber.
Headaches, Fatigue, and Upper Respiratory Infections
In clinical trials for plaque psoriasis, 13% of people on Skyrizi experienced upper respiratory infections (compared to about 10% on placebo), 3.5% reported headaches, and 2.5% reported fatigue. For people taking it for Crohn’s disease, the pattern was similar, with headaches affecting about 7% during the 12-week induction phase.
While the trials don’t report exactly how many days these effects lasted, headaches and fatigue from biologic medications generally behave like their everyday counterparts. A headache after an injection tends to resolve within a day or two. Fatigue may come and go in the first few days following a dose and often improves as your body adjusts over the first few treatment cycles.
Upper respiratory infections (think cold-like symptoms: congestion, sore throat, mild cough) follow typical cold timelines of 7 to 10 days. Skyrizi works by dialing down part of your immune response, which can make you slightly more prone to picking up these infections rather than making them last longer than usual.
Side Effects That May Persist During Treatment
Some side effects reported in longer studies don’t neatly resolve after a few days because they can recur with ongoing treatment. In the 52-week Crohn’s disease maintenance study, joint pain affected 8 to 9% of participants, abdominal pain occurred in 6 to 9%, and injection site reactions continued to appear in 5 to 6% of people at the higher dose. These numbers stayed relatively stable across the study period rather than climbing, which suggests the effects tend to come and go rather than progressively worsen.
A six-year follow-up study published in the Journal of the American Academy of Dermatology found that side effect rates remained low and consistent through 324 weeks (about six years) of continuous treatment. Importantly, no new safety signals emerged over that time. So while you may continue to experience occasional mild effects like joint aches or injection site irritation at each dose, the overall pattern doesn’t get worse the longer you stay on the drug.
How Long Side Effects Last After Stopping
Skyrizi’s half-life is 28 days for a typical 90 kg person. In practical terms, that means the drug concentration in your body drops by half roughly every four weeks after your last injection. It generally takes about five half-lives for a medication to be considered fully eliminated, which works out to approximately 20 weeks, or about five months.
Any side effects directly caused by the drug’s action on your immune system (like increased susceptibility to infections) can theoretically persist during that entire washout period, though they gradually diminish as the drug clears. Side effects that are more like acute reactions to the injection itself, such as headache, fatigue, or injection site soreness, won’t recur once you stop dosing.
Rare but Serious Reactions
Serious allergic reactions, including anaphylaxis, have been reported but are rare. These would happen shortly after an injection and require emergency care. Symptoms include swelling of the face, lips, or throat, difficulty breathing, chest tightness, dizziness, or widespread hives.
For people taking Skyrizi for Crohn’s disease, there is a small risk of liver injury. One reported case involved abnormal liver tests that developed after two intravenous induction doses. The liver abnormalities resolved after treatment with steroids, and the drug was discontinued. Signs to watch for include unexplained nausea, vomiting, abdominal pain, dark urine, yellowing of the skin or eyes, or unusual fatigue. These symptoms warrant prompt medical attention regardless of when they appear during treatment.
Infection Risk While on Skyrizi
Because Skyrizi suppresses a specific part of your immune system, you carry a modestly higher infection risk for as long as the drug is active in your body. This includes common infections like colds and urinary tract infections, as well as fungal skin infections (tinea), which affected about 1% of psoriasis trial participants compared to 0.3% on placebo.
Tuberculosis is a specific concern with this class of drugs. In clinical trials, 72 people with latent TB took Skyrizi alongside standard TB preventive treatment, and none developed active TB over an average follow-up of about 61 weeks. This is why your doctor tests for TB before starting treatment.
The key principle with infections on Skyrizi is straightforward: treat them normally, but pay attention if they don’t improve on schedule. A cold that drags on beyond two weeks, a fever that won’t break, or any infection that isn’t responding to standard treatment is a reason to contact your prescriber. The FDA label specifically notes that Skyrizi should be paused until any clinically significant infection resolves.