What is the next therapeutic option after a failed adalimumab (Humira) trial for moderate‑to‑severe psoriasis in an adult who has been screened for latent tuberculosis and hepatitis B/C and has no biologic contraindications?

Next Step After Adalimumab Failure in Moderate-to-Severe Psoriasis

Switch to an IL-23 inhibitor (guselkumab, risankizumab, or tildrakizumab) as the preferred next-line biologic therapy after adalimumab failure, with guselkumab demonstrating superior efficacy with 66.1% of adalimumab non-responders achieving PASI 90 at week 48. 1

Primary Recommendation: IL-23 Inhibitors

The 2019 AAD-NPF guidelines establish IL-23 inhibitors as the optimal choice following TNF inhibitor (adalimumab) failure based on direct comparative evidence 1:

• Guselkumab is the most strongly supported option, dosed at 100 mg subcutaneously at weeks 0,4, then every 8 weeks thereafter 1, 2

  • In the VOYAGE 2 trial, 70.0% of patients achieved PASI 90 at week 16 compared to 46.8% with adalimumab 1
  • Among adalimumab non-responders who switched to guselkumab, 66.1% achieved PASI 90 at week 48 1
  • This represents the highest quality evidence for switching after adalimumab failure 1

• Risankizumab (if FDA-approved in your region) demonstrates even higher efficacy rates 1

  • 77% achieved PASI 90 at week 12 (pooled 90-mg and 180-mg doses) 1
  • 45% achieved complete clearance (PASI 100) versus 18% with ustekinumab 1

• Tildrakizumab is an alternative IL-23 inhibitor, dosed at 100 mg at weeks 0,4, then every 12 weeks 1

Alternative Options: IL-17 Inhibitors

IL-17 inhibitors (secukinumab, ixekizumab, brodalumab) represent a second-tier option after adalimumab failure 1:

• The British Association of Dermatologists recommends considering secukinumab as an alternative when switching biologics 1
• All IL-17 antagonists have comparable efficacy given their similar mechanism of action 1
• Important caveat: Brodalumab carries a boxed warning for suicidal ideation and requires enrollment in a REMS program; avoid in patients with depression history or suicidal ideation 1
• Response should be assessed at 12 weeks of continuous therapy 1

When to Consider Alternative TNF Inhibitors

Switching to a different TNF inhibitor (etanercept or infliximab) is generally not the preferred strategy after adalimumab failure 1:

• The ACR/NPF guidelines conditionally recommend switching to a different mechanism (IL-23 or IL-17) over another TNF inhibitor after TNF failure 1
• However, infliximab may be reserved for very severe disease or when other biologics have failed 1
• Infliximab requires IV administration at 5 mg/kg at weeks 0,2,6, then every 8 weeks, and should be combined with methotrexate to reduce immunogenicity 1, 3

Combination Therapy Considerations

If the patient had a partial response to adalimumab (achieved some improvement but not meeting PASI 75 or DLQI improvement >5 points), consider 1, 3:

• Adding high-potency topical corticosteroids ± vitamin D analogues for 12-16 weeks 3
• Adding methotrexate to reduce immunogenicity and potentially enhance efficacy 1, 3
• However, switching to IL-23 inhibitor monotherapy is still preferred over combination therapy based on guideline recommendations 1

Assessment Timeline and Success Criteria

• Assess response to the new biologic at 12-16 weeks depending on the agent selected 1
• Treatment success is defined as achieving PASI 75 (75% improvement from baseline) OR PASI 50 (50% improvement) AND DLQI improvement >5 points 1
• If minimal response criteria are not met (PASI 50 + clinically relevant DLQI improvement), consider switching to another biologic class 1

Critical Pitfalls to Avoid

• Do not delay switching: Assess adalimumab response at 16 weeks; if inadequate, switch promptly rather than continuing ineffective therapy 1, 3
• Screen for contraindications: Before initiating IL-23 or IL-17 inhibitors, confirm TB, hepatitis B/C screening is current (as stated in your clinical scenario) 3
• Avoid brodalumab in patients with any history of depression, suicidal ideation, or recent suicidal behavior due to boxed warning 1
• Do not use systemic corticosteroids for psoriasis due to rebound flares upon discontinuation 3

Special Populations

For patients with psoriatic arthritis in addition to skin disease 1, 3:

• IL-23 inhibitors (guselkumab) and IL-17 inhibitors both treat joint and skin manifestations effectively 1
• The choice should prioritize the agent with best evidence for both skin and joint outcomes 1