Dr. Ahmed Atopic dermatitis or eczema is a heterogeneous skin disease with underlying inflammation and itchy skin that affects millions worldwide.
Managing eczema effectively often requires targeted treatments to control inflammation, reduce symptoms, and improve the patient’s quality of life.
Two major treatment categories for moderate-to-severe eczema include Dupixent (dupilumab), a biologic therapy, and traditional immunosuppressant medications like cyclosporine, methotrexate, and mycophenolate mofetil.
This article explores the differences between these treatment options, their mechanisms of action, effectiveness, side effects, and overall suitability for eczema management.
What is Dupixent?
Dupixent (dupilumab) is a biologic drug that targets interleukin-4 (IL-4) and interleukin-13 (IL-13), key cytokines involved in the immune response that contributes to eczema.
Dupixent helps reduce inflammation, itchiness, and skin damage by blocking these cytokines. Dupixent is administered via subcutaneous injection and is FDA-approved for moderate-to-severe atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps.
Unlike traditional treatments, Dupixent is not an immunosuppressant but rather a biological therapy that specifically modulates immune signaling pathways.
What Are Immunosuppressant Medications?
Immunosuppressants are drugs that suppress or regulate the immune system to decrease inflammation and autoimmune responses. These medications are traditionally used for conditions like organ transplantation and autoimmune diseases but have been repurposed for treating severe eczema.
Common immunosuppressants used for eczema include:
- Cyclosporine: A calcineurin inhibitor that suppresses T-cell activation, reducing inflammation quickly.
- Methotrexate: An antimetabolite that inhibits cell proliferation and inflammatory responses.
- Mycophenolate Mofetil (MMF): Works by inhibiting lymphocyte proliferation to modulate immune responses.
- Azathioprine: Interferes with DNA synthesis in immune cells, leading to reduced immune activity and inflammation.
These medications are usually prescribed when patients do not respond well to topical treatments or require systemic therapy for severe AD.
Dupixent vs Tacrolimus and Elidel (Pimecrolimus) for Atopic Dermatitis
Mechanism of Action
| Feature | Dupixent (Dupilumab) | Immunosuppressants |
| Target | IL-4 and IL-13 cytokines | Broad immune system suppression |
| Mode of Action | Selective immune modulation | General suppression of immune response |
| Administration | Subcutaneous injection (every 2-4 weeks) | Oral (pills) or intravenous |
| FDA Approval for Eczema | Yes | Off-label use for most immunosuppressants |
| Onset of Action | 2-4 weeks | Varies (weeks to months) |
Dupixent’s selective cytokine activity reduces inflammation in the skin without impairing immune function, as opposed to the universal immune suppression induced by immunosuppressants.
Although more rapid to act in certain instances, immunosuppressants need to be closely monitored because they are potentially toxic and cause side effects.
Efficacy and Safety
Clinical trials have shown that Dupixent significantly reduces eczema symptoms, including itch reduction, skin clearance, and quality of life. Patients on Dupixent remain in remission even after long-term use. [Ref]
Immunomodulators such as cyclosporine can be highly effective, but their effects can wane with time, necessitating dose adjustments or medication switches.
Real-world study confirms significant improvements in EASI scores, itch, and overall quality of life for patients using dupilumab. For example, a meta-analysis reported a weighted mean reduction in EASI score of 69.6% after 16 weeks of dupilumab therapy. [Ref]
Long-term real-world data supports the favorable safety profile of dupilumab, with low rates of serious adverse events. While conjunctivitis and injection site reactions remain common, the overall safety profile is considered acceptable for long-term use. [Ref]
On the contrary, multiple studies demonstrated that immunosuppressants, mainly Cyclosporin, result in end-organ toxicity; therefore, it is only recommended for short-term use, with continuous use only up to 2 years. [Ref]
In a real-world comparison study with 488 patients (including adults and adolescents), patients achieved EASI-50, EASI-75, and EASI-90 scores more rapidly with dupilumab than with methotrexate. Meanwhile, Cyclosporin showed similar efficacy as dupilumab. [Ref]
Another study on drug survival in children with AD suggested that treatment with methotrexate and Cyclosporin was associated with higher drug discontinuation rates due to inefficacy as compared to dupilumab. [Ref]
Dupixent Short-term and Long-Term Side effects
Side Effects and Risks
| Side Effect | Dupixent | Immunosuppressants |
| Infection Risk | Low | High (increased susceptibility to infections) |
| Organ Toxicity | None reported | Potential liver, kidney, or bone marrow toxicity |
| Cancer Risk | No known risk | Potential increased risk with long-term use |
| Common Side Effects | Injection site reactions, eye irritation | Nausea, fatigue, high blood pressure, kidney damage |
| Long-Term Safety | Considered safe for long-term use | Requires monitoring due to toxicity risks |
While Dupixent has a favorable safety profile, immunosuppressants carry significant risks. Long-term use of immunosuppressants can lead to liver and kidney damage, increased susceptibility to infections, and, in some cases, higher risks of malignancy.
Impact on Quality of Life
Eczema affects more than just the skin—it impacts daily activities, emotional well-being, and sleep. Dupixent users often report significant improvements in sleep quality and reduced stress related to constant itching.
Immunosuppressants can be effective in controlling flare-ups, but their side effects and the need for frequent monitoring may be burdensome for patients.
Cost and Accessibility
- Dupixent: Expensive without insurance coverage, but manufacturer assistance programs may help. Some patients may struggle to afford this treatment despite its efficacy.
- Immunosuppressants: Generally, these are more affordable but require frequent monitoring and lab tests, adding to costs over time. Many of these drugs are available in generic forms, making them a cost-effective choice for some patients.
Dupixent Pen Vs Syringe: What’s the Difference
What’s the Best Choice?
Dupixent is Ideal for Patients Who:
- Have moderate-to-severe eczema unresponsive to topical treatments.
- Prefer a targeted therapy with fewer systemic side effects.
- Require long-term maintenance treatment.
- Have a history of poor tolerance to immunosuppressants.
- Want a treatment with minimal risk of organ toxicity.
Immunosuppressants Are Suitable for Patients Who:
- Are in need of a fast-acting solution to treat severe flare-ups of eczema.
- Patients who are unable to pay for biologic therapies such as Dupixent.
- In patients who require a short-term treatment prior to transitioning to other long-term options.
Conclusion
Both Dupixent and standard immunosuppressant medications represent effective treatments for eczema; however, each presents dissimilar benefits and risks.
Again, Dupixent offers targeted and long-term treatment while producing fewer systemic side effects; hence, it is the drug of choice for many patients.
At the same time, immunosuppressants remain valuable for short-term issues and cases where biologics are inaccessible.
