What is Otezla (apremilast)?

What is Otezla (Apremilast)?

Otezla (apremilast) is an oral phosphodiesterase-4 (PDE-4) inhibitor approved for treating moderate to severe plaque psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet's disease. 1, 2

Mechanism of Action

• Apremilast inhibits PDE-4, which increases intracellular cyclic adenosine monophosphate (cAMP) levels, leading to downregulation of inflammatory responses involving T helper 1, T helper 17, and type 1 interferon pathways 3, 1
• The drug also modulates anti-inflammatory cytokines such as IL-10, further improving the inflammatory profile underlying psoriasis 3
• The specific mechanism by which apremilast exerts its therapeutic action is not fully defined 1

Approved Indications

• Psoriatic arthritis: Treatment of active psoriatic arthritis in adults, including both DMARD-naïve and DMARD-experienced patients 2, 4
• Plaque psoriasis: Treatment of moderate to severe plaque psoriasis in adults and pediatric patients ≥6 years weighing ≥20 kg who are candidates for phototherapy or systemic therapy 5
• Behçet's disease: Treatment of oral ulcers associated with Behçet's disease 5

Dosing and Administration

• Maintenance dose: 30 mg twice daily by mouth 3
• Titration schedule to minimize gastrointestinal side effects 3:
  • Day 1: 10 mg (AM)
  • Day 2: 10 mg (AM & PM)
  • Day 3: 10 mg (AM); 20 mg (PM)
  • Day 4: 20 mg (AM & PM)
  • Day 5: 20 mg (AM); 30 mg (PM)
  • Day 6 onward: 30 mg (AM & PM)
• Renal impairment: Reduce to 30 mg once daily in patients with severe renal impairment (creatinine clearance <30 mL/min) 3, 1
• Hepatic impairment: No dose adjustment needed for moderate or severe hepatic impairment 1

Key Advantages

• Oral administration: Convenient alternative to injectable biologics 3, 2
• No laboratory monitoring required: Unlike methotrexate and other systemic agents, apremilast does not require routine laboratory screening 3, 2
• Safe in liver disease: The American Academy of Dermatology notes that despite hepatic metabolism via cytochrome P450, apremilast does not cause hepatotoxicity, making it advantageous for patients with pre-existing liver disease 6

Common Adverse Effects

• Gastrointestinal symptoms (most common): Diarrhea (17.3%), nausea (15.7%) occurring in 70-80% of patients within the first 2 weeks, with 75-80% being mild and 60-65% resolving within the first month 3, 6, 7
• Upper respiratory tract infections (15.5%) and nasopharyngitis (14.4%) 3, 7
• Headache: Tension headache (9.0%) and headache (6.3%) 3, 7
• Weight loss: Occurs in 12% of patients; monitor regularly and consider discontinuation if >5% weight loss from baseline 3, 6
• Depression: May emerge or worsen in approximately 1% of patients; discuss this risk before initiating therapy 3, 6
• Dehydration risk: Elderly patients (≥65 years) are particularly prone to dehydration and its complications from GI side effects 3

Important Drug Interactions

• Strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin): Not recommended as they reduce apremilast efficacy by 72% (AUC) and 43% (Cmax) 3, 6, 1
• No significant interactions with oral contraceptives, ketoconazole, or methotrexate 1
• Apremilast is not an inhibitor or inducer of major CYP enzymes 1

Clinical Positioning

For psoriasis: Apremilast is appropriate for patients who prefer to avoid frequent injections and laboratory monitoring, and are willing to accept slower onset of skin clearance and lower likelihood of complete clearing compared to biologics 3

For psoriatic arthritis: According to EULAR 2020 guidelines, apremilast should be reserved for patients with mild disease (≤4 joints, lower disease activity, limited skin involvement) who have failed at least one csDMARD and for whom biologics or JAK inhibitors are not appropriate 3

• The EULAR 2016 guidelines note that apremilast's place is limited to patients who failed csDMARDs and for whom bDMARDs may not be appropriate, such as those with comorbidities, history of infections, or those preferring oral medication 3
• Apremilast shows moderate efficacy with ACR70 responses rarely seen and sometimes not different from placebo 3
• Radiographic data demonstrating disease-modifying potential are still lacking 3

Efficacy Data

• Psoriasis: Approximately 30% PASI-75 response rate at week 16, maintained through week 52 7
• Psoriatic arthritis: About 35% of patients achieve modest improvement in joint status versus 19% with placebo at 16 weeks 8
• Rapid symptom relief: Significant improvements in pruritus and skin discomfort/pain seen as early as week 2 2
• Also effective for difficult-to-treat nail, scalp, and palmoplantar psoriasis 2, 7

Special Populations

• Pregnancy: Should only be used if benefit justifies potential risk to fetus; apremilast distributes across the placenta 3, 1
• Lactation: Likely present in human milk based on animal data; consider benefits of breastfeeding versus maternal need for treatment 1
• Elderly: No dose adjustment needed, though 13% higher AUC observed; monitor closely for dehydration 1
• Pediatric: Approved for children ≥6 years weighing ≥20 kg with moderate to severe plaque psoriasis 5