What treatment options are available for a patient with a history of psoriasis and a recent severe infection caused by a resistant Gram-positive organism, considering the use of Apremilast (Otezla)?

Apremilast for Psoriasis with Recent Severe Resistant Gram-Positive Infection

Apremilast (Otezla) is the preferred systemic therapy for this patient with psoriasis and recent severe resistant Gram-positive infection, as it does not increase infection risk and requires no immunosuppression or laboratory monitoring. 1, 2

Why Apremilast is Optimal in This Clinical Context

Apremilast is specifically advantageous when biologics are contraindicated due to infection history. The 2018 ACR/NPF guidelines explicitly state that apremilast may be considered in patients with contraindications to TNF inhibitors, including recurrent infections. 3 The EULAR 2015 recommendations similarly position apremilast for patients "with comorbidities or a history of infections" where biologics may not be appropriate. 3

Safety Profile in High-Risk Patients

• No increased infection risk has been documented with apremilast, even in patients with serious baseline comorbidities. A systematic review of 841 psoriasis patients with serious baseline diseases (including chronic infections) found no infection reactivations or worsening documented with apremilast monotherapy. 2

• Apremilast is not contraindicated in active infections, unlike TNF inhibitors and other biologics which carry significant infection warnings. 2

• No laboratory monitoring is required, eliminating concerns about detecting early signs of infection progression or immunosuppression. 1, 4

Dosing and Initiation Protocol

Start with the mandatory 5-day titration schedule to minimize gastrointestinal side effects:

• Days 1-5: Titrate from 10 mg AM (Day 1) up to 30 mg twice daily by Day 6 using the FDA-approved schedule 1
• Maintenance: 30 mg twice daily starting Day 6, taken without regard to meals 1
• Do not crush, split, or chew tablets 1

Dose Adjustment for Renal Impairment

• If creatinine clearance <30 mL/min, reduce to 30 mg once daily and use only the AM titration schedule, skipping all PM doses 1

Expected Clinical Response Timeline

• Pruritus and skin discomfort improve as early as week 2 4
• Assess definitive response at week 16, when 59-70% of patients achieve PASI75 or satisfactory response (PASI50-75 with DLQI ≤5) 5
• Sustained efficacy documented up to 208 weeks in clinical trials 4

Critical Monitoring and Management

Gastrointestinal Side Effects (Most Common)

• 70-80% of patients experience GI symptoms within the first 2 weeks, but these typically resolve quickly 6
• Monitor patients >65 years and those on volume-depleting medications more closely, as they are at higher risk for complications from severe diarrhea, nausea, or vomiting 1
• Consider dose reduction or temporary suspension if severe GI symptoms develop; patients generally improve quickly upon dose adjustment 1

Weight and Psychiatric Monitoring

• Monitor body weight at each visit; if weight loss exceeds 5% from baseline, consider discontinuing apremilast 6
• Screen for depression before initiating and monitor at each visit, as depression occurs in approximately 1% of patients 7, 6
• Avoid apremilast if significant depression or history of suicidal ideation exists 7

Why NOT to Use Biologics in This Patient

Biologics carry substantial infection risk that is unacceptable given the recent severe resistant infection:

• TNF inhibitors are conditionally recommended only when patients do NOT have contraindications including recurrent infections 3
• Abatacept may be considered instead of TNF inhibitors in patients with recurrent or serious infections based on indirect evidence from RA populations showing fewer hospitalized infections 3
• IL-17 inhibitors should be avoided if history of recurrent Candida infections exists 3

Alternative Considerations Only if Apremilast Fails

If apremilast proves ineffective after 16 weeks:

• Consider abatacept as the safest biologic option given the infection history, based on ACR/NPF conditional recommendations for patients with recurrent or serious infections 3
• Avoid IL-17 inhibitors if any Candida history, as they increase fungal infection risk 3
• Methotrexate is NOT recommended given its immunosuppressive effects and the recent severe infection 3

Common Pitfalls to Avoid

• Do not skip the 5-day titration—this significantly increases GI side effects and early discontinuation 1
• Do not combine apremilast with biologics initially—combination therapy is only conditionally recommended when partial response to current therapy exists, not as first-line 3, 7
• Do not use systemic corticosteroids, as they can precipitate severe erythrodermic or pustular psoriasis flares upon discontinuation 8
• Do not assume apremilast is less effective—real-world data shows 70.4% of patients achieve PASI75 or satisfactory response by week 16 5