What biologic therapy is suitable for a patient with psoriasis vulgaris and a history of severe infections or malignancies?

Biologic Therapy for Psoriasis Vulgaris with History of Severe Infections or Malignancy

For patients with psoriasis vulgaris and a history of severe infections or malignancies, IL-12/23 inhibitors (specifically ustekinumab) or IL-17 inhibitors (secukinumab, ixekizumab) are preferred over TNF inhibitors, as they demonstrate no definitive evidence of increased malignancy risk and may carry lower infection risk profiles. 1, 2

Treatment Algorithm Based on Patient History

For Patients with History of Malignancy

First-line recommendation: IL-12/23 inhibitors (ustekinumab)

• There is no definitive evidence that ustekinumab used as monotherapy for moderate-to-severe psoriasis increases the risk of solid tumor or lymphoreticular malignancy. 1
• Patients with a history of solid tumor malignancy who have failed other therapies such as ultraviolet phototherapy, methotrexate, and/or acitretin may receive ustekinumab without expectation of increased risk of tumor recurrence. 1
• The largest real-world study (37 patients) demonstrated that secukinumab was the most frequently used biologic in cancer patients, with no disease progressions related to treatment. 3
• A single-center study of 16 psoriatic patients with malignant cancer diagnosed within the previous 10 years showed 100% achieved PASI 90 improvement with no cancer reactivation or new malignancies during 96 weeks of biologic treatment. 4

Second-line recommendation: IL-17 inhibitors (secukinumab, ixekizumab)

• IL-17 inhibitors demonstrated safety in oncologic patients, with anti-IL23p19 biologics (36%) and anti-IL-17 agents (16%) showing no cancer progression in a 31-patient cohort. 5
• The efficacy and safety profile of IL-23 and IL-17 inhibitors may be advantageous for oncologic patients compared to TNF inhibitors. 5

Avoid: TNF inhibitors in recent malignancy

• TNF-alpha inhibitors may cause a slightly increased risk of cancer, including nonmelanoma skin cancer and hematologic malignancies, though data remain inconclusive. 6
• Traditional systemic therapies (methotrexate, cyclosporine) may be associated with increased risk of lymphoproliferative disorders. 6

For Patients with History of Severe or Recurrent Infections

First-line recommendation: IL-12/23 inhibitors (ustekinumab) or IL-17 inhibitors

• The ACR/NPF guidelines conditionally recommend switching to IL-17 or IL-12/23 inhibitors over TNF inhibitors in patients with contraindications to TNF biologics, including recurrent infections, congestive heart failure, or demyelinating disease. 1
• In patients with active psoriatic arthritis and predominant enthesitis, guidelines recommend switching to an IL-17 inhibitor over a TNF inhibitor if the patient has severe psoriasis or contraindications to TNF biologics, including recurrent infections. 1
• Abatacept is conditionally recommended particularly for patients with recurrent serious infections where TNF inhibitors may be contraindicated. 7

Critical infection screening before any biologic:

• Pretreatment testing for latent tuberculosis (PPD, Quantiferon Gold, T-Spot) is mandatory, as TNF-alpha plays a key role in host defense against mycobacterial infection. 1
• The risk of tuberculosis with infliximab has been estimated to be approximately six times that of untreated patients, with risks potentially lower with etanercept. 1
• Serologic tests for hepatitis B and C (HB surface Ag, anti-HB surface Ab, anti-HB core Ab, and hepatitis C antibody tests) are required at baseline. 1
• Yearly testing for latent TB should be performed in patients at high risk (contact with active TB, travel to endemic areas, healthcare workers). 1

Avoid: TNF inhibitors in severe infection history

• Serious and opportunistic infections have been reported with anti-TNF agents, though overall infection rates in clinical trials were no greater than placebo. 1
• Infections and malignancy are significant clinical concerns with anti-TNF therapies, with previous or concomitant immunosuppressant treatment and PUVA therapy potentially compounding such risks. 1

Special Populations Requiring Additional Considerations

Patients with Congestive Heart Failure

• Anti-TNF agents should be avoided in patients with severe (NYHA class III or IV) congestive heart failure. 1
• IL-17 or IL-12/23 inhibitors are preferred alternatives in this population. 1

Patients with Demyelinating Disease

• TNF inhibitors are contraindicated in patients with demyelinating disease. 1
• IL-17 or IL-12/23 inhibitors should be selected instead. 1

Patients with Inflammatory Bowel Disease

• Critical pitfall: IL-17 inhibitors appear to cause exacerbations and new cases of inflammatory bowel disease. 8
• For patients with concomitant active IBD, monoclonal antibody TNF inhibitors or ustekinumab (IL-12/23 inhibitor) are preferred. 1
• Avoid IL-17 inhibitors entirely in patients with known IBD. 1, 8

Dosing Considerations for Ustekinumab

• In subjects weighing 100 kg or less, response rates were comparable with both 45 mg and 90 mg doses. 2
• In subjects weighing greater than 100 kg, higher response rates were seen with 90 mg dosing compared with 45 mg dosing (71% vs 49% PASI 75 response). 2
• Overweight or obese patients often need the higher dose (90 mg) of ustekinumab to achieve the response of lower-weight patients taking the 45 mg dose. 1

Monitoring Requirements

• Periodic history and physical examination, including screening for nonmelanoma skin cancer, is required for all biologics. 1
• CBC and comprehensive metabolic panel should be obtained at baseline. 1
• Referral for chest radiography in cases with positive TB test is mandatory. 1
• Referral to an infectious disease specialist should be considered on a case-by-case basis, particularly in immunocompromised patients. 1

Common Pitfalls to Avoid

• Never combine two biologic agents simultaneously due to unpredictable immune dysregulation and lack of safety data. 7
• Do not use IL-17 inhibitors in patients with inflammatory bowel disease, as they may cause disease exacerbation. 8
• Avoid TNF inhibitors in patients with NYHA class III or IV heart failure, demyelinating disease, or recent serious infections. 1
• Do not initiate any biologic without completing tuberculosis screening and hepatitis serologies. 1
• PUVA combined with cyclosporine significantly accelerates skin cancer development and should be avoided. 6