Skyrizi For Crohn’s Disease: How It Works, Side Effects, & More

When I was deep in the thick of Crohn’s flare-ups I had symptoms like bleeding, urgency, and that constant edge-of-your-seat feeling. I kept hearing the same thing from doctors: “You need to start a biologic.” One of the names that kept popping up was Skyrizi. At the time, I hadn’t tried any biologics, and I wasn’t ready to. But I was curious. What exactly is Skyrizi? How does it work? And is it something people actually see results with?

This post breaks it all down from the perspective of someone who never went the biologic route, but spent over a decade researching gut health, experimenting with diet and lifestyle, and talking to others on the same healing path. Whether you’re considering Skyrizi for IBD, trying to avoid it, or just want to understand what it does, here’s everything I’ve learned.

Skyrizi (risankizumab) is a biologic medication that’s been making its way into more Crohn’s treatment plans. It was originally developed for plaque psoriasis, then approved for psoriatic arthritis, and eventually for moderate to severe Crohn’s disease. It works by targeting a specific protein in the immune system called interleukin-23 (IL-23), which plays a role in inflammation, especially in the gut.

Unlike some older drugs that suppress broader parts of the immune system, Skyrizi is more targeted. The idea is to block one piece of the inflammatory chain reaction, so symptoms settle without completely shutting down your defenses. Whether that actually plays out in the real world is where opinions start to diverge.

In Crohn’s disease, the immune system basically gets confused and attacks the digestive tract. IL-23 is one of the proteins involved in that faulty immune response. By blocking IL-23, Skyrizi aims to interrupt the process that causes chronic gut inflammation.

The treatment is divided into two phases. First, there’s the induction phase, which includes several high-dose IV infusions to try and get inflammation under control. After that, the maintenance phase kicks in, with injections every couple of months to keep symptoms from coming back.

What interested me about Skyrizi when I first heard about it was that it’s designed to work with precision almost like a scalpel instead of a sledgehammer. But at the end of the day, it’s still a pharmaceutical tool that affects your immune system, and that wasn’t the path I chose. I had to dig deep and figure out another way (more on that below).

There are some decent numbers behind Skyrizi if you look at the clinical trials. In the ADVANCE study, about 45% of patients hit clinical remission at 12 weeks, compared to 25% in the placebo group. That’s not a miracle cure, but it’s a promising response rate, especially for people who hadn’t found relief with other drugs.

In the maintenance trial (FORTIFY), the people who responded well during induction were more likely to stay in remission with continued Skyrizi treatment. Endoscopic healing rates also improved, which means there was less visible inflammation in the gut lining, something doctors look at during colonoscopies.

Of course, those are averages. Some people respond better than others, and some don’t respond at all. I’ve read stories from people who said Skyrizi changed their life, and others who said it didn’t touch their symptoms.

Let’s talk about side effects, because this is one of the reasons I never jumped into biologics. Even though Skyrizi is considered “safer” by some, it still has its list.

The most common side effects reported include things like headaches, fatigue, upper respiratory infections, and mild injection site irritation. More serious risks (though less common) include fungal or bacterial infections and allergic reactions.

One concern I’ve always had with any biologic is the potential for long-term immune suppression. Skyrizi is more selective than drugs like Humira or Remicade, but anytime you’re messing with the immune system, there are trade-offs. I took a different route to avoid having to make that trade at all.

The typical schedule looks like this:

• Induction phase: 600 mg by IV infusion at weeks 0, 4, and 8
• Maintenance phase: 360 mg via subcutaneous injection every 8 weeks starting at week 12

From what I’ve read in support groups and forums, the induction infusions are usually done in a clinic, and then you self-administer injections at home. People say the injector pen is easy to use, and most don’t have issues with pain or discomfort.

For someone who prefers to avoid hospitals (like I did), I can see why the ability to shift to home injections might be appealing.

When comparing Skyrizi to other biologics, a few differences stand out.

• Skyrizi vs Humira: Humira targets TNF-alpha, and while it works well for many, others build up antibodies over time. Skyrizi, being IL-23 specific, avoids that pathway entirely.
• Skyrizi vs Stelara: Stelara blocks both IL-12 and IL-23, while Skyrizi only blocks IL-23. Some say that makes Skyrizi more focused, though it depends on your specific immune response.
• Skyrizi vs Entyvio: Entyvio works mostly in the gut. It doesn’t impact the whole body like systemic biologics do, which is appealing to a lot of people who are trying to minimize side effects.

Personally, I never made it to this decision point. Instead, I focused on finding a way to get into remission without using any of these drugs. For those who want to explore that path, I’ve put together The GutMellow Remission Roadmap, a full breakdown of the diet, supplements, and lifestyle shifts I used to get off the flare-up rollercoaster.

There are plenty of stories floating around online from real people using Skyrizi for Crohn’s. Some of them are pretty encouraging. I’ve seen folks talk about finally feeling “normal” again after months of non-stop flares. Others mention fewer bathroom trips, more energy, and better quality of life overall.

But I’ve also seen people say the improvements didn’t last, or that they never felt a major change to begin with. A few dealt with side effects like fatigue or cold-like symptoms that stuck around longer than expected.

For me, patient stories were always more useful than clinical data. That’s how I pieced together my own approach, by learning from others, testing things out, and refining what worked for my body.

Skyrizi is expensive without insurance. Like, thousands of dollars per dose expensive. But most people don’t pay that. Insurance coverage has improved now that it’s FDA-approved for Crohn’s, especially if you’ve tried other treatments and they haven’t worked.

There’s also the Skyrizi Complete Savings Program, which helps lower out-of-pocket costs for eligible patients. Some even get the drug for as little as $5 per dose, depending on their insurance.

When I was making my decision years ago, I looked into the costs and support programs just in case. Ultimately, I chose to invest in high-quality food, testing, and supplements instead. It wasn’t cheap either but for me, it felt more sustainable long-term.

Skyrizi tends to be prescribed to people with moderate to severe Crohn’s who haven’t responded well to other treatments. It’s usually not the first thing doctors reach for unless there’s a clear need for something new.

If someone’s already gone through TNF blockers or vedolizumab (Entyvio) and is still flaring, Skyrizi might be on the table. There are also some limitations if someone has a history of infections or certain cancers, and it hasn’t been studied as much in pregnancy.

Again, this wasn’t my route but I understand why some people go this way. Everyone’s journey is different, and sometimes medications are the only thing keeping symptoms under control. I just knew I wanted to exhaust every natural option first.

After a decade of trial and error, I finally found a combination of strategies that actually worked. I went from constant flare-ups to long-term remission, without biologics or surgery. I created GutMellow to share my experience and help others navigate their own healing journey.

The GutMellow Remission Roadmap includes everything I wish I had when I was first diagnosed. It’s a comprehensive resource that outlines the exact steps I took to regain control of my gut health, including:

This blog is for informational and educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. While I am sharing my personal experience, every individual’s health journey is unique. Always consult with a qualified healthcare professional before making any changes to your diet, supplements, medications, or lifestyle. Healing is a personal journey, and what worked for me may not work for everyone.