Psoriasis is a chronic autoimmune condition that causes skin cells to build up rapidly, resulting in thick, red, and scaly patches on the skin. For moderate-to-severe cases, biologic drugs can significantly manage symptoms by targeting specific parts of the immune system. Two such options, Humira (adalimumab) and Skyrizi (risankizumab), are often considered. While both are effective, they are not identical in their approach or results, making a direct comparison essential for patients and healthcare providers.
Understanding the Mechanisms: IL-23 vs. TNF Inhibitors
Humira and Skyrizi work differently because they target different inflammatory pathways in the immune system. This difference is a primary factor in their varying efficacy and side effect profiles.
Humira: The TNF-alpha Inhibitor
Humira is a tumor necrosis factor (TNF) inhibitor, meaning it blocks the action of TNF-alpha, a protein that plays a key role in systemic inflammation. By blocking TNF-alpha, Humira reduces inflammation and alleviates psoriasis symptoms. However, since TNF-alpha is involved in many immune functions, blocking it can have broader effects on the body's immune system. Humira was approved by the FDA in 2002 and is used for a wide range of inflammatory conditions beyond psoriasis, such as rheumatoid arthritis and Crohn's disease.
Skyrizi: The IL-23 Inhibitor
Skyrizi, a more recent addition to biologic treatments, is an interleukin-23 (IL-23) inhibitor. It works by selectively targeting and blocking IL-23, a protein that is crucial in promoting the inflammatory response specific to psoriasis. This selective mechanism may offer a more targeted and effective approach for skin clearance with potentially fewer off-target immune effects compared to broader-acting agents like TNF inhibitors.
Efficacy Comparison: The IMMvent Clinical Trial
A head-to-head Phase 3 clinical trial known as IMMvent directly compared Skyrizi and Humira for adults with moderate-to-severe plaque psoriasis. The results showed a significant difference in skin clearance rates between the two medications at 16 weeks.
- Higher skin clearance: At 16 weeks, 72% of patients on Skyrizi achieved 90% clearer skin (PASI 90), compared to only 47% of patients on Humira.
- Complete skin clearance: 40% of Skyrizi patients achieved 100% skin clearance (PASI 100) after 16 weeks, compared to just 7% of Humira patients.
- Switching efficacy: For Humira patients who did not achieve at least 90% skin clearance after 16 weeks and were then switched to Skyrizi, 66% achieved a PASI 90 score by week 44. This was in contrast to only 21% of those who remained on Humira.
Comparing Dosage and Convenience
Beyond efficacy, the dosing schedule is a key consideration that impacts patient convenience and adherence.
- Humira dosing: For psoriasis, Humira is typically administered as an injection every other week after the initial starter dose. This results in approximately 25 maintenance injections per year.
- Skyrizi dosing: Skyrizi offers a much less frequent dosing schedule. After two initial starter doses four weeks apart, maintenance injections are required only every 12 weeks, or four times per year.
For many patients, the significant reduction in the number of annual injections with Skyrizi is a major factor in improving their quality of life and treatment compliance.
Weighing Safety and Side Effects
As with all potent medications, both Humira and Skyrizi carry risks of side effects. Both suppress the immune system and therefore increase the risk of serious infections.
Humira (Adalimumab) Side Effects
Common side effects for Humira include:
- Injection site reactions
- Headache
- Upper respiratory tract infections
- Sinusitis
Humira also carries boxed warnings for rare but serious side effects, including nervous system effects and potential cancer risks, though risk levels for different cancers vary.
Skyrizi (Risankizumab) Side Effects
Common side effects for Skyrizi include:
- Upper respiratory infections
- Headache
- Fatigue
- Injection site reactions
- Tinea (fungal) infections
Comparison of Humira and Skyrizi for Psoriasis
| Feature | Humira (Adalimumab) | Skyrizi (Risankizumab) |
|---|---|---|
| Mechanism of Action | Tumor necrosis factor (TNF) inhibitor; broader anti-inflammatory effect. | Interleukin-23 (IL-23) inhibitor; more targeted pathway. |
| Efficacy (IMMvent Trial) | 47% achieved PASI 90 at 16 weeks. | 72% achieved PASI 90 at 16 weeks. |
| Dosing Frequency | Every 2 weeks (after initial dose). | Every 12 weeks (after initial doses). |
| Injection Site Reactions | Common. | Common. |
| Common Side Effects | Headaches, rash, infections. | Infections, headache, fatigue, fungal infections. |
| Serious Side Effects | Risk of serious infections, nervous system issues, potential cancer risks. | Risk of serious infections. |
| Approved Uses | Broad range of inflammatory conditions, including psoriasis, psoriatic arthritis, rheumatoid arthritis, and Crohn's disease. | Psoriasis, psoriatic arthritis, and Crohn's disease. |
| Biosimilar Availability | Several biosimilars available. | Currently only available as a brand-name medication. |
The Clinical Decision: Which One is Right for You?
Choosing between Humira and Skyrizi is a decision that requires a personalized assessment in consultation with a dermatologist. Skyrizi has shown superior efficacy for clearing skin and offers the benefit of less frequent dosing, which is often a strong preference for patients. However, factors like a patient's overall health profile, history with other treatments, and insurance coverage play a crucial role.
Humira, as a more established biologic with a broader range of indications, may be suitable for patients with co-existing conditions like psoriatic arthritis, where Humira's mechanism provides benefits for joint inflammation. Additionally, the availability of Humira biosimilars can sometimes lead to lower costs depending on insurance coverage, although costs can be high for both without adequate coverage. The existence of biosimilars introduces a new layer of complexity to the medication landscape.
Ultimately, a patient's response to treatment can vary. Some may find greater success with one over the other, and clinical data, like that from the IMMvent trial, provides a strong starting point for discussion. It's important to have an open conversation with your healthcare provider to evaluate all these factors and decide on the best course of action.
Conclusion
In the competition for the best treatment for moderate-to-severe plaque psoriasis, Skyrizi has demonstrated superior efficacy and a more convenient dosing schedule compared to the more established Humira. Skyrizi's more targeted mechanism may also be an advantage for some patients. However, Humira remains a valuable treatment, especially for those with multiple inflammatory conditions, and has a longer track record. The ideal choice depends on individual patient factors and a thorough discussion with a qualified healthcare professional, who can weigh the clinical data and personal needs to determine the most effective path forward. For a deeper understanding of the clinical evidence, including trial results for switching patients, refer to the Skyrizi HCP website.
