Otezla (Apremilast) for Plaque Psoriasis and Psoriatic Arthritis
Otezla (apremilast) is recommended at 30 mg twice daily (after a 5-day titration) for adults with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, and for active psoriatic arthritis. 1
Dosing Regimen
Standard Titration Schedule
The medication requires a specific 5-day titration to minimize gastrointestinal side effects 2, 1:
- Day 1: 10 mg AM only
- Day 2: 10 mg AM, 10 mg PM
- Day 3: 10 mg AM, 20 mg PM
- Day 4: 20 mg AM, 20 mg PM
- Day 5: 20 mg AM, 30 mg PM
- Day 6 and thereafter: 30 mg AM, 30 mg PM (maintenance dose) 2, 1
Tablets should be swallowed whole without crushing, splitting, or chewing, and can be taken without regard to meals. 1
Dose Adjustment for Renal Impairment
In patients with severe renal impairment (creatinine clearance <30 mL/min), reduce the dose to 30 mg once daily. 2, 1 For initial titration in this population, use only the AM schedule from the titration table and skip all PM doses. 1
Clinical Efficacy
Plaque Psoriasis
Apremilast achieves PASI-75 (75% reduction in Psoriasis Area and Severity Index) in approximately 30-33% of patients at 16 weeks. 3, 4 While this efficacy is lower than many biologics, apremilast offers the advantage of oral administration without requiring laboratory monitoring. 2
The medication is effective for difficult-to-treat areas including scalp, nail, and palmoplantar psoriasis. 5, 4 Importantly, pruritus improvement can be seen as early as week 2 of treatment. 5
Psoriatic Arthritis
Apremilast 30 mg twice daily improves signs and symptoms in both DMARD-naïve and DMARD-experienced patients with active psoriatic arthritis. 5 The medication also improves enthesitis, dactylitis, physical function, and fatigue, with efficacy sustained for up to 208 weeks. 5
Critical Safety Considerations
Gastrointestinal Effects
The most common adverse effects are diarrhea (17.3%), nausea (15.7%), and headache. 2, 4 Severe diarrhea, nausea, and vomiting requiring hospitalization have been reported postmarketing, particularly in the first few weeks of treatment. 1
Patients 65 years and older are at higher risk for dehydration and its complications from gastrointestinal side effects. 2 Monitor these patients closely and consider dose reduction or temporary suspension if severe GI symptoms develop. 1
Depression Risk
Apremilast may be associated with emergence or worsening of depression. 2 Discuss this risk with patients before initiating therapy, and carefully weigh risks versus benefits in patients with a history of depression or suicidal ideation. 1
Weight Loss
A small percentage of patients may lose weight on apremilast. 2 Monitor weight regularly, and if weight loss exceeds 5% from baseline, consider discontinuing apremilast. 2
Drug Interactions
Apremilast is metabolized by cytochrome P450, and concurrent use with strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended due to decreased efficacy. 2 Review medication lists before initiating therapy and periodically thereafter. 2
Laboratory Monitoring
Routine laboratory screening and monitoring can be considered on an individual basis, but is not required. 2 This represents a significant advantage over many systemic therapies for psoriasis. 2
Combination Therapy
There is currently no strong evidence to support combined use of apremilast with other systemic or phototherapy treatments for psoriasis. 2 However, limited data suggest apremilast can be safely combined with biologic agents in patients not responding adequately to biologics alone. 6
When used in combination with biologics like ustekinumab or etanercept, apremilast may augment efficacy, though this is based on lower-quality evidence. 2
Special Populations
Pregnancy
Apremilast should only be used in pregnancy if the benefit justifies the potential risk to the fetus. 2
Clinical Positioning
Apremilast is most appropriate for patients who prefer to avoid frequent injections and laboratory monitoring, and who are willing to accept slower onset of skin clearance and lower likelihood of complete clearing compared to biologics. 2 The medication offers the convenience of oral administration with a favorable safety profile that does not require routine laboratory surveillance. 2