Apremilast is an orally administered small molecule approved for the treatment of immune-mediated inflammatory conditions. It is classified as a selective phosphodiesterase 4 (PDE4) inhibitor, with anti-inflammatory properties beneficial in conditions such as psoriatic arthritis (PsA), moderate to severe plaque psoriasis, and oral ulcers associated with Behçet’s disease.
Indications
Apremilast is FDA-approved for the following indications:
- Moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy.
- Active psoriatic arthritis in adults.
- Oral ulcers in Behçet’s disease.
While not yet approved for pediatric use or off-label for other autoimmune conditions, studies are underway exploring its potential in hidradenitis suppurativa, lupus erythematosus, and atopic dermatitis.
Notable Clinical Consideration (2025):
Apremilast may be particularly suitable for patients with comorbidities that limit biologic therapy—such as prior malignancy, chronic infections (e.g., HIV, Hepatitis B or C), demyelinating disorders, or congestive heart failure.
Mechanism of Action
Apremilast exerts its anti-inflammatory effect through selective inhibition of PDE4, the predominant phosphodiesterase in immune cells. This inhibition:
- Increases intracellular cyclic AMP (cAMP) levels.
- Downregulates pro-inflammatory cytokines, including:
- TNF-α
- IL-17
- IL-23
- IFN-γ
- Upregulates anti-inflammatory cytokines like IL-10.
This shift reduces inflammation in both skin and joints, improving clinical outcomes without broad immunosuppression.
Dosage and Titration
| Day | Morning Dose | Evening Dose |
|---|---|---|
| Day 1 | 10 mg | — |
| Day 2 | 10 mg | 10 mg |
| Day 3 | 10 mg | 20 mg |
| Day 4 | 20 mg | 20 mg |
| Day 5 | 20 mg | 30 mg |
| Day 6 and onward | 30 mg | 30 mg |
- Maintenance Dose: 30 mg PO twice daily.
- No food restrictions; may be taken with or without meals.
- Tablets should not be crushed or split.
Clinical Evidence (2025 Update)
- ESTEEM 1 & 2 Trials: Showed significant improvement in Psoriasis Area and Severity Index (PASI-75) scores at week 16 vs placebo.
- PALACE Trials: Demonstrated sustained improvement in ACR20 responses and physical function in PsA patients over 5 years.
- RELIEF Study: Confirmed efficacy in reducing oral ulcers in Behçet’s disease, with symptom relief seen as early as week 2.
Common Adverse Effects
- Gastrointestinal:
- Diarrhea (17–19%)
- Nausea (17%)
- Neurologic:
- Headache (12%)
- Others:
- Upper respiratory tract infection
- Weight loss
- Depression and mood disturbances
GI side effects usually occur within the first 2 weeks and typically resolve without discontinuation.
Serious Risks & Precautions
- Weight Loss:
- Monitor weight periodically.
- Discontinue if unexplained weight loss >10% of baseline occurs.
- Depression & Suicidal Ideation:
- Screen patients with history of depression.
- Discontinue if mood worsens.
- Use in Pregnancy:
- Category C. Animal studies show teratogenic effects.
- Use only if potential benefit justifies potential fetal risk.
- Avoid in women trying to conceive.
Drug Interactions
Strong CYP3A4 inducers may significantly reduce apremilast efficacy. Avoid co-administration with:
- Carbamazepine
- Phenytoin
- Phenobarbital
- Rifampin
- St. John’s Wort
Contraindications
- Known hypersensitivity to apremilast.
- Severe hepatic impairment (limited data).
- Children under 18 years (not FDA-approved).
- Pregnancy and lactation (weigh risk/benefit carefully).
Storage
- Store at ≤30°C (86°F).
- Protect from excessive moisture.
- Keep in original container until ready to use.
Brand Names
- Otezla® (originator by Amgen)
- Available globally with generic options in select regions.
Conclusion
Apremilast represents a non-biologic, orally administered immunomodulatory therapy with a favorable safety profile. It offers a biologic-sparing option particularly advantageous for patients in whom injectable therapies are contraindicated or poorly tolerated.
As more long-term data emerge, especially in the context of comorbid populations, apremilast continues to play an important role in the personalized management of chronic inflammatory dermatologic and rheumatologic diseases.
References:
- Mease PJ, et al. Lancet Rheumatol. 2024;6(3):e148-e158.
- Papp KA, et al. J Am Acad Dermatol. 2023;89(4):749-758.
- FDA Label for Otezla (Apremilast) – Revised 2025.
- ClinicalTrials.gov (NCT04632640, NCT05234868)