What are the next treatment options for a 50-year-old patient with psoriasis not responding to Enstilar (calcipotriene and betamethasone dipropionate) and brittle diabetes (unstable diabetes mellitus)?

Next Treatment Options for Psoriasis Unresponsive to Enstilar in a Patient with Brittle Diabetes

TNF-alpha inhibitors (adalimumab, etanercept, or infliximab) are the preferred next-line systemic therapy for this patient, as they have no known drug interactions, no deleterious effects on renal function or blood pressure, and no significant impact on glucose control when diabetes is well-managed. 1

Rationale for TNF-Alpha Inhibitors as First Choice

• Biologic therapies offer significant advantages in patients with complex medical histories on multiple medications, with no relevant drug interactions with TNF-alpha antagonists and no known deleterious effects on renal function or blood pressure 1
• In patients with active psoriatic disease and diabetes, TNF inhibitors may be considered when diabetes is well controlled, particularly if the patient has severe or extensive skin disease 1
• TNF-alpha inhibitors are FDA pregnancy category B and have fewer significant safety issues compared to traditional systemic agents 1

Why Traditional Systemic Agents Are Less Suitable

Methotrexate (MTX)

• MTX carries increased hepatotoxicity risk in patients with diabetes due to potential underlying steatohepatitis, making it a less attractive option 1
• The most commonly used systemic agent worldwide, but requires careful monitoring of liver enzymes and blood counts 1
• Should be avoided or used with extreme caution in diabetic patients with any degree of hepatic dysfunction 1

Cyclosporine

• Cyclosporine has high probability of exacerbating hypertension (common comorbidity in diabetic patients) and is nephrotoxic 1
• Traditionally used only as a "rescue" medication, approved for maximum 1 year continuous therapy 1
• Has potential drug interactions through cytochrome P450 3A4 system 1

Acitretin

• Acitretin causes elevations in serum transaminases (up to 16% of patients) and triglycerides (25-50% of patients), which are particularly problematic in diabetic patients who often have dyslipidemia 1
• Less effective as monotherapy, often requiring doses exceeding 25 mg/d with dose-dependent side effects 1

Alternative Biologic Options

IL-17 Inhibitors (Secukinumab, Ixekizumab)

• IL-17 inhibitors may be conditionally recommended over TNF inhibitors in patients with diabetes, based on very-low-quality evidence 1
• Secukinumab (COSENTYX) is administered subcutaneously with loading doses followed by maintenance every 4 weeks 2
• Ixekizumab (TALTZ) dosing: 160 mg at Week 0, then 80 mg every 2 weeks 3
• Both agents increase infection risk, particularly upper respiratory tract infections, oral candidiasis, and fungal infections 3, 2

IL-12/23 Inhibitors (Ustekinumab)

• May be preferred over TNF inhibitors in diabetic patients based on conditional recommendation from very-low-quality evidence 1
• Generally well-tolerated with favorable safety profile 1

Critical Monitoring Requirements for Brittle Diabetes

• Screen for tuberculosis before initiating any biologic therapy 3, 2
• Monitor closely for signs and symptoms of infection during treatment, as biologics increase infection risk 3, 2
• Discontinue biologic therapy if serious infection develops until infection resolves 3
• Ensure all age-appropriate immunizations are completed before starting biologics; avoid live vaccines during treatment 3

Common Pitfalls to Avoid

• Never use systemic corticosteroids, as they can precipitate severe psoriasis flares upon discontinuation 1, 4
• Avoid medications that worsen psoriasis: lithium, chloroquine, beta-blockers, and NSAIDs 1, 5, 4
• Do not assume topical therapy failure without trying alternative topical agents first, as some patients respond to different formulations 1, 4
• Avoid cyclosporine in patients with any degree of renal impairment or uncontrolled hypertension, both common in brittle diabetics 1

Special Consideration: Pioglitazone

• Pioglitazone (30 mg) demonstrated significant improvement in PASI 75 scores (risk difference = 0.42; 95% CI: 0.18-0.65) and may be considered as adjunctive therapy in diabetic patients with psoriasis 6
• This provides dual benefit of improving both glucose control and psoriasis severity 6
• 30 mg dose showed significantly higher PASI 75 response than 15 mg dose (P = 0.003) 6

Treatment Algorithm

1. Ensure adequate trial of topical therapy: Confirm Enstilar was used appropriately (adequate duration, proper application technique) 7, 8, 9

2. Assess diabetes control: If diabetes is well-controlled, proceed with TNF inhibitor; if poorly controlled, optimize diabetes management first while considering pioglitazone for dual benefit 1, 6

3. First-line systemic: Initiate TNF-alpha inhibitor (adalimumab, etanercept, or infliximab) 1

4. Alternative if TNF contraindicated or failed: Consider IL-17 inhibitor (secukinumab or ixekizumab) or IL-12/23 inhibitor (ustekinumab) 1, 3, 2

5. Avoid: Methotrexate (hepatotoxicity risk), cyclosporine (nephrotoxicity, hypertension), acitretin (lipid abnormalities) 1