What is the recommended dosing schedule, contraindications, renal dose adjustment, monitoring parameters, and alternative therapy options for Otezla (apremilast) in an adult with moderate‑to‑severe plaque psoriasis (or active psoriatic arthritis) who is a candidate for systemic therapy?

Otezla (Apremilast) for Moderate-to-Severe Plaque Psoriasis and Psoriatic Arthritis

Recommended Dosing Schedule

Apremilast requires a mandatory 5-day titration schedule starting at 10 mg daily and increasing by 10 mg increments to reach the maintenance dose of 30 mg twice daily. 1

Titration Schedule

• Day 1: 10 mg once daily (morning)
• Day 2: 10 mg twice daily (morning and evening)
• Day 3: 10 mg morning, 20 mg evening
• Day 4: 20 mg twice daily
• Day 5: 20 mg morning, 30 mg evening
• Day 6 onward: 30 mg twice daily (maintenance dose) 2, 3

Duration of Therapy

• Continue apremilast for a minimum of 8 weeks to achieve desired results 3
• Optimal total duration is approximately 24 weeks for better efficacy 3
• Efficacy is sustained for up to 52 weeks and beyond 2, 4, 5

Contraindications

Apremilast has no absolute contraindications listed in major guidelines, but requires caution in patients with depression history. 1

Key Precautions

• Discuss the risk of depression with patients before initiating therapy, as depression occurs in approximately 1% of patients 1
• Monitor for emergence or worsening of depression at each visit 1
• Avoid concomitant use with strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin) as they reduce apremilast efficacy 1

Renal Dose Adjustment

Reduce the apremilast dose to 30 mg once daily if creatinine clearance is <30 mL/min. 1

• No dose adjustment is required for mild-to-moderate renal impairment 1
• For severe renal impairment (CrCl <30 mL/min), use only the morning dose of 30 mg daily 1
• A baseline renal assessment is prudent for patients with known renal disease to guide dose adjustment 1

Monitoring Parameters

Apremilast requires no routine laboratory monitoring, making it advantageous for patients with access barriers or needle phobia. 1

Clinical Monitoring at Each Visit

• Body weight: Discontinue apremilast if weight loss exceeds 5% from baseline 1
  • Weight loss of 5-10% occurs in approximately 12% of patients versus 5% on placebo 1
• Depression screening: Monitor for mood changes at every visit 1
• Hydration status: Elderly patients are particularly prone to dehydration from gastrointestinal effects and may require hospitalization 1

Laboratory Monitoring

• No routine CBC, liver function tests, or renal function tests are required 1
• Apremilast does not cause bone marrow suppression or hepatotoxicity, unlike methotrexate 1
• Avoid ordering routine labs "just to be safe" as this adds unnecessary cost and patient burden without clinical benefit 1

Adverse Effects Management

Gastrointestinal Effects (Most Common)

• Diarrhea and nausea occur in 70-80% of patients within the first 2 weeks 1
• 75-80% of gastrointestinal events are mild and 60-65% resolve within the first month without intervention 1, 4
• Consider prolonged titration over 4 weeks (instead of 5 days) to reduce adverse effects 3

Other Common Adverse Effects

• Upper respiratory tract infections and headache 1
• Insomnia 4
• Depression (1% of patients) 1

Alternative Therapy Options

For moderate-to-severe plaque psoriasis, biologics are first-line treatment due to superior efficacy, with apremilast positioned as an alternative for patients who cannot use biologics. 6

Biologic Alternatives (First-Line for Moderate-to-Severe Disease)

• TNF-α inhibitors: Etanercept (50 mg twice weekly for 12 weeks, then 50 mg weekly), adalimumab, infliximab (5 mg/kg at weeks 0,2,6, then every 8 weeks) 7, 6
• IL-12/IL-23 inhibitors: Ustekinumab (45 mg if <100 kg, 90 mg if ≥100 kg at weeks 0,4, then every 12 weeks) 7
• IL-17 inhibitors 6
• IL-23 inhibitors 6

Traditional Systemic Alternatives

• Methotrexate: Requires CBC and liver function monitoring every 3-4 months 1
• Acitretin: Considered negligibly immunosuppressive 7
• Cyclosporine: Requires monitoring 1

Combination Therapy Options

Apremilast may be combined with other agents when monotherapy is insufficient:

• Topical corticosteroids with or without vitamin D analogues 7
• Biologics (etanercept, infliximab, ustekinumab) to augment efficacy 7
• Acitretin 7
• Methotrexate 7

Positioning of Apremilast in Treatment Algorithm

Apremilast is effective as monotherapy in stable mild-to-moderate psoriasis and in combination for severe psoriasis. 3

Ideal Candidates for Apremilast

• Patients with moderate-to-severe plaque psoriasis who cannot undergo regular laboratory monitoring 1, 3
• Patients with pre-existing liver disease or complex medical comorbidities 1
• Patients with difficult-to-treat areas (scalp, palms, soles, nails) 2, 3
• Patients with psoriatic arthritis (both DMARD-naïve and DMARD-experienced) 2
• Obese patients, patients with hepatitis B or C, HIV, or patients on polypharmacy 3

Efficacy Benchmarks

• At week 16,33.1% of patients achieve PASI-75 5
• At week 24,47.5% achieve PASI-75,30% achieve PASI-90, and 10% achieve PASI-100 4
• At week 52,25% achieve PASI-75,35% achieve PASI-90, and 10% achieve PASI-100 4
• 60% of patients achieve and maintain DLQI 0-1 from week 24 through week 52 4
• Significant improvements in pruritus and skin discomfort/pain occur as early as week 2 2, 8

Common Pitfalls to Avoid

• Do not reduce the apremilast dose for hepatic impairment; dose adjustment is indicated only for severe renal impairment 1
• Do not order routine laboratory monitoring; focus on clinical monitoring of weight and depression 1
• Do not discontinue therapy before 8 weeks, as adequate time is needed to assess response 3
• Do not use apremilast with strong CYP450 inducers, as they reduce efficacy 1
• Do not ignore weight loss >5% from baseline; this requires discontinuation 1