Skyrizi (risankizumab) is not a TNF inhibitor. It belongs to a different class of biologics called interleukin-23 (IL-23) inhibitors. While both drug classes treat some of the same conditions, they work through entirely different mechanisms, and IL-23 inhibitors like Skyrizi have largely replaced TNF inhibitors as the go-to biologic treatments for conditions like plaque psoriasis.
How Skyrizi Works
TNF inhibitors, like adalimumab (Humira) and etanercept (Enbrel), block a protein called tumor necrosis factor-alpha, which drives widespread inflammation throughout the body. Skyrizi takes a more targeted approach. It’s a monoclonal antibody that binds to the p19 subunit of interleukin-23, a specific immune signaling protein involved in driving the overactive immune responses behind psoriasis, inflammatory bowel disease, and related conditions.
By blocking IL-23 from connecting with its receptor, Skyrizi shuts down a narrower piece of the immune cascade. Importantly, it does not interfere with IL-12, a related protein that shares a structural component with IL-23. This selectivity is part of what distinguishes it from older biologics that cast a wider net over the immune system.
What Skyrizi Treats
The FDA has approved Skyrizi for four conditions:
- Moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
- Active psoriatic arthritis in adults
- Moderately to severely active Crohn’s disease in adults
- Moderately to severely active ulcerative colitis in adults
TNF inhibitors are also approved for several of these conditions, which is one reason people often compare the two classes. But being approved for the same disease doesn’t make them the same type of drug.
Skyrizi vs. TNF Inhibitors: Effectiveness
In head-to-head clinical trials against adalimumab (Humira), one of the most widely used TNF inhibitors, Skyrizi came out ahead for plaque psoriasis. In the IMMvent trial, 72% of patients on Skyrizi achieved 90% skin clearance at 16 weeks, compared to 47% on adalimumab. For an overall clear or almost-clear skin rating, the numbers were 84% for Skyrizi versus 60% for adalimumab.
The trial also tested what happened when patients who had a middling response to adalimumab switched to Skyrizi. Among those who switched, 66% reached 90% skin clearance by week 44, compared to just 21% of those who stayed on adalimumab. Real-world data from a large Italian study tracked patients over three years and found that about 75% of people on Skyrizi achieved complete skin clearance by year three, with improvements continuing well past the first year.
Side Effect Differences
Because Skyrizi and TNF inhibitors target different parts of the immune system, their side effect profiles look somewhat different. Both commonly cause headaches and injection site reactions like redness, swelling, or bruising.
Side effects more specific to Skyrizi include upper respiratory infections, fatigue, and fungal skin infections like athlete’s foot, ringworm, or jock itch. TNF inhibitors like Humira tend to come with a broader list of potential issues, including nausea, vomiting, diarrhea, stomach pain, and cold symptoms. Humira also carries warnings for more serious concerns like heart rhythm changes, easy bruising or bleeding, and neurological symptoms such as numbness, tingling, or muscle weakness. Both Skyrizi and TNF inhibitors can interact with live vaccines, so you’ll need to plan around that if immunizations are coming up.
How Dosing Compares
One practical advantage of Skyrizi for psoriasis and psoriatic arthritis is the dosing schedule. After two initial doses four weeks apart, you take a subcutaneous injection (a shot under the skin, typically self-administered at home) just once every 12 weeks. TNF inhibitors like adalimumab typically require injections every one to two weeks, which means significantly more frequent dosing.
For Crohn’s disease and ulcerative colitis, the schedule is more involved. Treatment starts with IV infusions given at a clinic at weeks 0, 4, and 8. After that initial phase, you switch to at-home injections every 8 weeks. The doses for these gut conditions are substantially higher than for psoriasis, reflecting the different level of immune activity that needs to be managed in the digestive tract.
Why This Distinction Matters
If you’re comparing treatment options or your doctor has mentioned switching from a TNF inhibitor to Skyrizi, understanding that these are fundamentally different drug classes is useful. Some people don’t respond well to TNF inhibitors, or they stop working over time. Switching to an IL-23 inhibitor like Skyrizi isn’t just trying another version of the same thing. It’s engaging a completely different pathway in the immune system, which is why patients who plateau on a TNF inhibitor can still see strong results after switching.