What is Otezla (apremilast)?

What is Otezla (Apremilast)?

Otezla (apremilast) is an oral phosphodiesterase-4 (PDE4) inhibitor approved for treating moderate-to-severe plaque psoriasis and active psoriatic arthritis in adults. 1

Mechanism of Action

Apremilast works intracellularly by inhibiting PDE4, which increases cyclic adenosine monophosphate (cAMP) levels inside immune cells. 1 This modulates the production of pro-inflammatory and anti-inflammatory mediators involved in psoriasis and psoriatic arthritis, though the exact therapeutic mechanism is not fully defined. 1

Pharmacokinetics

• Absorption: Oral bioavailability is approximately 73%, with peak plasma concentrations occurring around 2.5 hours after administration. 1
• Metabolism: Extensively metabolized primarily through CYP3A4, with minor contributions from CYP1A2 and CYP2A6. 1
• Elimination: Terminal half-life is 6-9 hours, with about 58% excreted in urine and 39% in feces. 1
• Protein binding: Approximately 68% bound to plasma proteins. 1

Dosing

• Standard dose: 30 mg twice daily after a 5-day titration schedule to minimize gastrointestinal side effects. 2
• 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

Clinical Efficacy

For Psoriasis:

• Approximately 30% of patients achieve PASI-75 response at week 16, with efficacy maintained through week 52. 4, 5
• Effective for difficult-to-treat areas including nail, scalp, and palmoplantar psoriasis. 4
• Rapid improvement in pruritus observed as early as week 2. 4

For Psoriatic Arthritis:

• About 35% of patients achieve at least modest improvement in joint status at 16 weeks (versus 19% with placebo). 6
• Improves enthesitis, dactylitis, physical function, and fatigue. 4
• Efficacy sustained for up to 208 weeks. 4
• Early onset of action with significant ACR20 response at week 2. 4

Safety Profile and Monitoring

Key advantage: No routine laboratory monitoring required. 3 This makes apremilast particularly useful for patients with access barriers, needle phobia, or inability to undergo regular lab testing. 3

Common adverse effects (occurring in first 2 weeks):

• Diarrhea (17.3%) and nausea (15.7%) - most are mild and 60-65% resolve within the first month. 3, 5
• Upper respiratory tract infections (15.5%). 5
• Headache (6.3-9.0%). 5

Important monitoring parameters:

• Weight: Monitor at each visit, as 12% of patients experience 5-10% weight loss. 3 Discontinue if weight loss exceeds 5% from baseline. 3
• Depression: Screen before initiating therapy and monitor at each visit, as depression occurs in approximately 1% of patients. 3
• Elderly patients: Monitor for dehydration from gastrointestinal effects, which may require hospitalization. 3

Notable safety features:

• Does not cause bone marrow suppression or require CBC monitoring (unlike methotrexate). 3
• No hepatotoxicity reported, making it advantageous for patients with pre-existing liver disease. 3

Drug Interactions

• Strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin) reduce apremilast efficacy by 72% and should be avoided. 3, 1
• No significant interactions with oral contraceptives, ketoconazole, or methotrexate. 1

Clinical Positioning

The American College of Rheumatology recommends:

• Starting TNF inhibitors over apremilast for treatment-naive patients with predominant enthesitis, though apremilast may be considered if patients prefer oral therapy or have contraindications to biologics (recurrent infections, congestive heart failure, demyelinating disease). 7
• Adding apremilast to current therapy over switching to apremilast monotherapy when patients show partial response to their current treatment. 8

Combination therapy:

• Can be combined with infliximab to augment efficacy, though long-term safety data are limited. 7
• May be combined with topical corticosteroids and vitamin D analogues. 7

Common Pitfalls to Avoid

• Do not order routine labs "just to be safe" - this adds unnecessary cost and patient burden without clinical benefit. 3
• Do not skip the 5-day titration schedule - this is mandatory to minimize gastrointestinal side effects. 2
• Do not use in patients with significant depression or suicidal ideation history without careful risk-benefit assessment. 8
• Do not combine with strong CYP450 inducers as this significantly reduces efficacy. 3, 1