Navigating Autoimmune Treatment: Enbrel and Skyrizi
Autoimmune diseases occur when the body's immune system mistakenly attacks its own cells. Conditions like plaque psoriasis, psoriatic arthritis, and rheumatoid arthritis are driven by underlying inflammation caused by this immune response. Biologic medications have revolutionized the treatment of these diseases by targeting specific components of the immune system. Enbrel (etanercept) and Skyrizi (risankizumab) are two prominent injectable biologics, but they work in fundamentally different ways and are not interchangeable. A thorough understanding of their unique properties is crucial for healthcare providers and patients when deciding on the most appropriate therapy.
What is Enbrel (Etanercept)?
Enbrel, with the generic name etanercept, is a biologic medication that has been on the market since its FDA approval in 1998. It belongs to a class of drugs known as tumor necrosis factor (TNF) inhibitors. TNF-alpha is a cytokine, a type of protein, that plays a central role in promoting systemic inflammation. In autoimmune diseases, an overproduction of TNF can lead to the chronic inflammation that causes symptoms.
Enbrel works by binding to TNF molecules and blocking them from interacting with their receptors on the cell surface. This action renders the TNF biologically inactive, thereby reducing the inflammatory cascade. Because of its broad anti-inflammatory effect, Enbrel is approved to treat a range of conditions:
- Moderately to severely active rheumatoid arthritis (RA)
- Moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in patients ages 2 and older
- Psoriatic arthritis (PsA)
- Ankylosing spondylitis (AS)
- Chronic moderate to severe plaque psoriasis (PsO) in adults
Administration is typically a subcutaneous injection, with dosing frequency determined by the specific condition being treated. As an immunosuppressant, Enbrel increases the risk of serious infections, and its label includes warnings about potential malignancies and neurologic events.
What is Skyrizi (Risankizumab)?
Skyrizi (risankizumab-rzaa) is a newer biologic, first approved by the FDA in 2019. It operates differently from Enbrel, belonging to a class called interleukin-23 (IL-23) inhibitors. Interleukins are another group of cytokines that regulate immune responses. Specifically, IL-23 is a key protein that drives inflammation in several autoimmune conditions, including psoriasis and Crohn's disease.
Skyrizi works by selectively targeting and blocking IL-23, which helps to reduce the inflammation that causes disease symptoms. This targeted mechanism of action is a key differentiator from the broader immunosuppression of TNF inhibitors. Skyrizi is approved for use in adults for several conditions:
- Moderate to severe plaque psoriasis
- Active psoriatic arthritis
- Moderately to severely active Crohn's disease
- Moderately to severely active ulcerative colitis
One of the most significant differences for patients is the dosing schedule. For psoriasis and psoriatic arthritis, after initial starter doses, Skyrizi is administered as a subcutaneous injection less frequently than Enbrel. For Crohn's and ulcerative colitis, treatment begins with intravenous infusions followed by subcutaneous maintenance doses. Like other biologics, Skyrizi carries an increased risk of infections.
Head-to-Head Comparison: Enbrel vs. Skyrizi
While both drugs treat overlapping conditions like plaque psoriasis and psoriatic arthritis, their differences in mechanism, dosing, and approved uses are significant.
- Mechanism of Action: The primary difference is their target. Enbrel is a TNF inhibitor, providing broad anti-inflammatory action. Skyrizi is an IL-23 inhibitor, offering a more targeted approach to inflammation.
- Dosing Frequency: Skyrizi's less frequent dosing for psoriasis/psoriatic arthritis is a major point of contrast with Enbrel's typical once-weekly injections. This can be a significant factor for patient convenience and adherence.
- Approved Uses: Enbrel has a longer history and is approved for conditions like rheumatoid arthritis and juvenile idiopathic arthritis, for which Skyrizi is not. Conversely, Skyrizi is approved for Crohn's disease and ulcerative colitis, which are not indications for Enbrel.
- Pediatric Use: Enbrel is approved for use in children as young as two for certain conditions, whereas Skyrizi is currently approved only for adults.
- Safety Profile: Both medications suppress the immune system and increase the risk of infection, requiring screening for tuberculosis (TB) before starting therapy. Enbrel also carries warnings about potential cancer risks and nervous system effects, which are not highlighted in the same way for Skyrizi.
Comparison Table: Enbrel vs. Skyrizi
| Feature | Enbrel (etanercept) | Skyrizi (risankizumab) |
|---|---|---|
| Drug Class | TNF alfa inhibitor | Interleukin-23 (IL-23) inhibitor |
| Mechanism | Blocks the inflammatory protein TNF-alpha. | Selectively blocks the inflammatory protein IL-23. |
| Approved Uses | RA, JIA (ages 2+), PsA, AS, Plaque Psoriasis. | Plaque Psoriasis, PsA, Crohn's Disease, Ulcerative Colitis (adults only). |
| Administration | Subcutaneous injection. | Subcutaneous injection or Intravenous infusion (for Crohn's/UC induction). |
| Dosing (PsO/PsA) | Typically once weekly. | Less frequent than Enbrel, after initial doses. |
| Common Side Effects | Injection site reactions, infections, headache, nausea. | Upper respiratory infections, headache, fatigue, injection site reactions. |
| FDA Approval | November 1998. | April 2019. |
Making a Treatment Choice
The decision between Enbrel and Skyrizi is complex and must be made in consultation with a healthcare professional. Factors influencing the choice include the specific condition being treated, disease severity, previous treatments, and patient preference, particularly regarding dosing frequency. For a patient with both psoriatic arthritis and Crohn's disease, Skyrizi would be a potential option, whereas for a patient with rheumatoid arthritis, Enbrel would be considered. A patient prioritizing fewer injections might prefer Skyrizi's less frequent schedule over Enbrel's weekly one. Cost and insurance coverage also play a significant role, as both are expensive specialty medications.
Conclusion
Enbrel and Skyrizi are both effective biologic medications for treating several autoimmune diseases, but they are not the same. Enbrel is a long-established TNF inhibitor with a broad range of applications, including pediatric use, and typically requires weekly injections. Skyrizi is a newer, more targeted IL-23 inhibitor with a notably less frequent dosing schedule for psoriasis and psoriatic arthritis, and it is also approved for inflammatory bowel diseases. The best choice depends on an individual's specific medical condition, history, and a collaborative decision with their doctor.
