Search. Learn. Save

Platform for Pharmaceutical Products for Healthcare Professionals
Search By
☰ Generic Formulas

Generic Formulas X

Apremilast

Apremilast

Apremilast: A Targeted Therapy for Chronic Inflammatory Diseases

Introduction

Chronic inflammatory diseases like psoriasis and psoriatic arthritis are not just skin-deep—they significantly impair patients' quality of life and can lead to joint damage and systemic complications if left untreated. Traditionally, these conditions were managed with immunosuppressants and biologics, but over the past decade, Apremilast has emerged as a unique, oral, targeted therapy that offers a new approach to disease control without the immunosuppressive risks of biologics. Apremilast, marketed under the brand name Otezla, is a small molecule that modulates inflammation by inhibiting an enzyme called phosphodiesterase 4 (PDE4). Approved by the FDA in 2014, Apremilast is widely used for treating moderate to severe plaque psoriasis, psoriatic arthritis, and oral ulcers in Behçet's disease.

Apremilast:

Apremilast is a selective PDE4 inhibitor developed for the treatment of chronic inflammatory conditions. PDE4 is a key regulator of cyclic AMP (cAMP) levels in immune cells. By inhibiting PDE4, Apremilast increases intracellular cAMP, which in turn reduces the production of pro-inflammatory cytokines like TNF-α, IL-17, and IL-23 while enhancing the production of anti-inflammatory cytokines such as IL-10.

Basic Drug Info

  • Brand Name: Otezla

  • Drug Class: PDE4 Inhibitor

  • Approval: FDA (2014)

  • Form: Oral tablets (10 mg, 20 mg, 30 mg)

  • Dosing: Typically 30 mg twice daily after titration

Mechanism of Action

The pathogenesis of psoriasis and psoriatic arthritis involves overactive immune signaling, especially in pathways involving TNF-α, IL-23, IL-17, and interferon-gamma. PDE4 is the dominant phosphodiesterase in immune cells that breaks down cAMP, a molecule that modulates inflammation.

By inhibiting PDE4, Apremilast:

  • Increases intracellular cAMP

  • Activates protein kinase A (PKA)

  • Suppresses transcription of inflammatory cytokines

  • Enhances anti-inflammatory cytokines

This results in a broad modulation of immune responses, reducing inflammation without the direct immunosuppression associated with traditional drugs or biologics.

Clinical Indications

Apremilast is FDA-approved for three major inflammatory conditions:

1. Plaque Psoriasis

  • Used for moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

  • Particularly helpful in difficult-to-treat areas such as scalp, nails, and genitals.

2. Psoriatic Arthritis

  • Approved for active psoriatic arthritis, either alone or in combination with DMARDs (e.g., methotrexate).

  • Improves joint pain, stiffness, and swelling, and slows down radiographic progression.

3. Oral Ulcers in Behçet’s Disease

  • Effective in reducing the frequency and severity of oral ulcers associated with Behçet's, an autoinflammatory disorder.

Off-Label and Investigational Uses

Researchers are exploring Apremilast’s anti-inflammatory potential in other chronic diseases, including:

  • Atopic dermatitis

  • Ankylosing spondylitis

  • Systemic lupus erythematosus

  • Inflammatory bowel disease (IBD)

  • Lichen planus

  • Hidradenitis suppurativa

While not yet FDA-approved for these indications, early-phase trials show promise.

Dosage and Administration

Initial Titration Schedule (To Reduce GI Side Effects)

Day Morning Evening
1 10 mg -
2 10 mg 10 mg
3 10 mg 20 mg
4 20 mg 20 mg
5 20 mg 30 mg
6+ 30 mg 30 mg

Note: Dosage should be reduced in patients with severe renal impairment (30 mg once daily).

Pharmacokinetics

Property Value
Bioavailability ~73% (oral)
Peak Plasma Time 2.5 hours
Half-life ~6–9 hours
Metabolism Liver (CYP3A4 mainly, also CYP1A2, CYP2A6)
Excretion Urine (58%), Feces (39%)

Apremilast’s pharmacokinetics allow for twice-daily oral dosing without the need for therapeutic drug monitoring.

Clinical Efficacy

1. ESTEEM Trials (Psoriasis)

  • ESTEEM 1 & 2 demonstrated significant PASI-75 response at 16 weeks vs. placebo.

  • Also showed sustained efficacy in long-term extension studies.

2. PALACE Trials (Psoriatic Arthritis)

  • PALACE 1-3 showed significant improvement in ACR20 response.

  • Decreased swollen/tender joint count and improved physical function (HAQ-DI).

3. RELIEF Trial (Behçet’s Disease)

  • Apremilast significantly reduced oral ulcer count and pain in patients with Behçet’s.

Benefits of Apremilast

1. Oral Administration

Patients prefer oral therapy over injections, making Apremilast more acceptable, especially for long-term use.

2. No Need for Monitoring

Unlike methotrexate or biologics, Apremilast does not require:

  • CBC or liver function tests

  • TB testing before initiation

  • Regular lab monitoring

3. Favorable Safety Profile

Minimal risk of:

  • Serious infections

  • Malignancy

  • Liver or kidney toxicity

4. Weight Loss Benefit

In overweight patients, modest weight loss (~2-3 kg) may be seen, which can be beneficial in managing comorbidities.

Side Effects and Adverse Reactions

1. Gastrointestinal

  • Nausea and diarrhea are most common (especially during titration).

  • Usually mild to moderate and self-limiting.

2. Weight Loss

  • Seen in ~10–15% of patients.

  • Should be monitored in underweight individuals.

3. Neuropsychiatric Effects

  • Depression, mood changes, and insomnia reported in a small number of patients.

  • Caution advised in those with a history of depression or suicidal ideation.

4. Headache and Fatigue

  • Common but generally tolerable.

Drug Interactions

1. CYP3A4 Inducers

Strong inducers (e.g., rifampin, carbamazepine, phenytoin) reduce Apremilast plasma concentration significantly → Avoid co-use.

2. Other Drugs

  • No significant interactions with methotrexate, NSAIDs, corticosteroids, or biologics.

  • Can be safely combined in multi-drug regimens.

Contraindications and Cautions

Condition Recommendation
Pregnancy Not recommended (Category C)
Lactation Avoid (not enough data)
Severe Renal Impairment Dose adjustment required
Depression Monitor closely
Pediatric Use Not approved under 18 years

Comparison with Other Therapies

Feature Apremilast Methotrexate Biologics (e.g., Adalimumab)
Route Oral Oral Injection
Monitoring Not required Required TB screening, labs
Infection Risk Low Moderate High
Onset of Action Moderate (4–12 weeks) Moderate Rapid
Cost High Low Very high
Convenience High Moderate Low (injection)

Apremilast fills a niche for patients who:

  • Want oral therapy

  • Are not eligible for biologics

  • Require a safer profile

Real-World Evidence

Since its approval, Apremilast has demonstrated effectiveness in real-world settings, especially in:

  • Elderly patients

  • Patients with multiple comorbidities (e.g., diabetes, hypertension)

  • Those with biologic failure or intolerance

It has also shown to improve quality of life scores, reduce work productivity loss, and maintain long-term disease control with continued use.

Limitations

Despite its many strengths, Apremilast has some limitations:

  • Modest efficacy compared to biologics

  • GI side effects can affect adherence

  • High cost without insurance coverage

  • Not suitable for rapid disease control in severe flares

Future Directions

1. Extended Indications

Ongoing trials are evaluating Apremilast in:

  • Pediatric psoriasis

  • Lichen sclerosus

  • Crohn’s disease and ulcerative colitis

2. Combination Therapy

Studies are examining combination regimens with:

  • Topical agents (e.g., corticosteroids)

  • Biologics for enhanced efficacy

3. New Formulations

  • Modified-release tablets for once-daily dosing

  • Topical PDE4 inhibitors with similar mechanisms

Conclusion

Apremilast represents a significant advancement in the treatment of chronic inflammatory diseases, particularly psoriasis and psoriatic arthritis. With its oral route, safety profile, and minimal monitoring requirements, it fills an important therapeutic gap between traditional systemic drugs and biologics. While it may not match the efficacy of high-powered biologics in severe cases, Apremilast offers an excellent option for patients who prefer oral therapy, have milder disease, or are not suitable candidates for immunosuppressive treatments.

Avaiable Medicines