What is the preferred treatment for a cancer patient on nivolumab with a severe psoriasis flare, TNF alpha inhibitors or IL 17 inhibitors like secukinumab?

IL-17 Inhibitors Are Preferred Over TNF-Alpha Inhibitors for Severe Psoriasis Flares in Cancer Patients on Nivolumab

For a cancer patient on nivolumab experiencing a severe psoriasis flare, IL-17 inhibitors (specifically secukinumab) should be the first-line systemic biologic choice over TNF-alpha inhibitors. 1

Primary Recommendation

When psoriasis becomes dose-limiting to cancer therapy in patients receiving checkpoint inhibitors like nivolumab, the treatment algorithm clearly prioritizes IL-12/23 inhibitors (ustekinumab) or IL-17 inhibitors (secukinumab, ixekizumab) as first-line options, with TNF inhibitors relegated to second-line status. 1

Evidence Supporting IL-17 Inhibitors in This Context

Safety Profile in Cancer Patients

• Secukinumab has demonstrated safety in cancer patients, with the largest available case series (37 patients) showing no disease progressions related to biologic treatment in psoriatic patients with previous malignancy diagnoses. 2

• Real-world evidence from three cancer patients with pre-existing psoriatic arthritis receiving checkpoint inhibitors (anti-PD-1 or combined anti-CTLA-4/PD-1) showed that IL-17/IL-23 axis inhibition maintained disease remission while preserving anti-tumor efficacy, with two complete remissions and one stable disease outcome. 3

• This is critical because targeting the IL-17/IL-23 axis appears to effectively control psoriasis/psoriatic arthritis during ICI exposure without compromising cancer treatment outcomes. 3

Efficacy Considerations

• Secukinumab demonstrates superior efficacy compared to TNF inhibitors, with 79% of patients achieving PASI 90 at week 16 with the 300 mg dose, maintained through 52 weeks. 1, 4

• The recommended dosing is 300 mg subcutaneously at weeks 0,1,2,3, and 4, followed by 300 mg every 4 weeks, which is more effective than the 150 mg dose. 1, 4

• IL-17 inhibitors have shown superiority over both etanercept (a TNF inhibitor) and ustekinumab in clinical trials for moderate-to-severe plaque psoriasis. 5

Why TNF Inhibitors Are Second-Line

The treatment algorithm explicitly lists TNF inhibitors (infliximab, etanercept, adalimumab, golimumab) as second-line options when IL-12/23 or IL-17 inhibitors are used first. 1 This hierarchy exists because:

• Unknown effects on immunotherapy efficacy: The guideline emphasizes concern about unknown effects of immunomodulators on targeted cancer therapies and immunotherapies in already-immunosuppressed cancer patients. 1

• Less robust evidence in checkpoint inhibitor context: While TNF inhibitors have established roles in psoriasis treatment generally, the specific evidence supporting their safety and efficacy in patients receiving checkpoint inhibitors is less compelling than for IL-17 inhibitors. 2, 3

Practical Implementation Algorithm

Step 1: Assess Severity and Impact

• Determine if psoriasis is dose-limiting to cancer therapy (i.e., severe enough to potentially require modification of nivolumab treatment). 1
• Evaluate number of nails involved if nail psoriasis is present (>3 nails warrants systemic therapy). 1

Step 2: Pre-Treatment Screening

• Screen for active tuberculosis before initiating secukinumab. 4
• Assess for active infections or sepsis; if present, consult infectious disease before starting therapy. 4
• Check for untreated hepatitis B (relative contraindication). 4
• Assess for inflammatory bowel disease history, as IL-17 inhibitors should be avoided in active IBD. 1

Step 3: Initiate IL-17 Inhibitor (Secukinumab)

• Secukinumab 300 mg subcutaneously at weeks 0,1,2,3, and 4, then every 4 weeks. 1, 4
• Self-administration is standard. 4
• Coordinate with oncology team given the patient's immunotherapy status. 1

Step 4: Monitor Response and Safety

• Assess definitive response after 12 weeks of continuous therapy. 1
• Monitor for mucocutaneous candida infections (most common adverse event at 1.9 per 100 patient-years, typically mild and responsive to standard treatment). 4
• Watch for serious infections (rare at 0.015 per patient-year) requiring treatment discontinuation. 4
• Continue monitoring cancer treatment response with oncology. 3

Important Caveats and Contraindications

Absolute Contraindications to IL-17 Inhibitors

• Active inflammatory bowel disease: Secukinumab showed lack of efficacy and increased adverse events in Crohn's disease trials. 1
• History of allergic reaction to the therapeutic agent. 1

When to Consider TNF Inhibitors Instead

TNF inhibitors may be preferred if the patient has:

• Active or history of inflammatory bowel disease (monoclonal antibody TNF inhibitors like infliximab, adalimumab are efficacious for IBD, whereas IL-17 inhibitors are contraindicated). 1
• Concomitant uveitis requiring treatment (monoclonal antibody TNF inhibitors prevent uveitis recurrence; etanercept shows contradictory results). 1
• Contraindications to IL-17 inhibitors. 1

Special Consideration: Brodalumab

• While brodalumab is an IL-17 receptor A antagonist with broader IL-17 family blockade, it carries a boxed warning for suicidal ideation and completed suicides, requiring prescribing through the SILIQ REMS program. 1, 6
• Avoid brodalumab in patients with suicidal ideation, recent suicidal behavior, or history of suicidal ideation. 1
• Given these restrictions and the availability of secukinumab and ixekizumab without such warnings, brodalumab should not be first-line. 1

Combination Therapy Considerations

• Monotherapy with IL-17 inhibitors is recommended over combination with methotrexate or other immunosuppressants in this population. 1
• If partial response occurs, consider adding topical corticosteroids or vitamin D analogs rather than additional systemic agents, though published safety data on combinations are lacking. 1, 4
• Never combine two biologics due to unknown risks and lack of supporting evidence. 4

Long-Term Management

• Maintain secukinumab every 4 weeks for sustained response. 1, 4
• If sustained remission is achieved, tapering of the biologic can be considered, though complete discontinuation leads to high flare rates. 1
• Coordinate all treatment decisions with the oncology team given the complex interplay between psoriasis treatment and checkpoint inhibitor therapy. 1, 3