What are all medications that inhibit interleukin‑23 for patients with autoinflammatory conditions?

IL-23 Inhibitors for Autoinflammatory Conditions

The FDA-approved IL-23 inhibitors for autoinflammatory conditions include guselkumab, tildrakizumab, and risankizumab, with ustekinumab targeting both IL-12 and IL-23 through their shared p40 subunit. 1

Currently Available IL-23 Inhibitors

Selective IL-23p19 Inhibitors

These agents specifically target the p19 subunit of IL-23:

• Guselkumab (Tremfya) - FDA-approved July 2017

  • Fully human IgG1 lambda monoclonal antibody blocking the p19 subunit
  • Dosing: 100 mg subcutaneous injection at week 0, week 4, then every 8 weeks
  • Approved for moderate-to-severe plaque psoriasis and psoriatic arthritis 1, 2

• Tildrakizumab (Ilumya) - FDA-approved March 2018

  • Humanized IgG1 monoclonal antibody targeting the p19 subunit
  • Dosing: 100 mg subcutaneous injection at week 0, week 4, then every 12 weeks
  • Requires in-office physician administration
  • Approved for moderate-to-severe plaque psoriasis 1

• Risankizumab - FDA-approved for psoriasis and Crohn's disease

  • Humanized IgG1 monoclonal antibody selectively inhibiting IL-23 via p19 binding
  • Demonstrated superior efficacy compared to ustekinumab in clinical trials
  • Approved for moderate-to-severe Crohn's disease 1, 3, 4

Dual IL-12/IL-23 Inhibitor

• Ustekinumab (Stelara) - FDA-approved September 2009
  • Human monoclonal antibody binding the shared p40 subunit of both IL-12 and IL-23
  • Dosing: Weight-based (45 mg for ≤100 kg; 90 mg for >100 kg) at week 0, week 4, then every 12 weeks
  • Approved for moderate-to-severe plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis 1, 3, 5

Additional IL-23 Inhibitors in Development

Several other IL-23p19 inhibitors are being investigated for inflammatory bowel disease and other autoinflammatory conditions:

• Mirikizumab (LY3074828) - Phase 2/3 trials in ulcerative colitis and Crohn's disease 3, 5, 6
• Brazikumab (MEDI2070) - Under investigation for ulcerative colitis 5, 6
• Guselkumab - Additional trials ongoing for inflammatory bowel disease beyond psoriatic indications 3, 5, 6
• Icotrokinra - Novel oral IL-23 receptor antagonist peptide in development for plaque psoriasis 7

Clinical Considerations

Response Assessment

Definitive response to IL-23 inhibitors should be assessed after 12 weeks of continuous therapy 1. For partial responders, consider dose escalation or adding topical therapies, methotrexate, or phototherapy, though combination data are limited 1.

Safety Profile

Phase III studies demonstrate IL-23 inhibitors are generally well-tolerated with increased infection risk (particularly upper respiratory infections and nasopharyngitis) 1, 8. Rare cases of elevated liver transaminases have occurred 1. The combination with methotrexate may increase infection risk 1.

Important Caveats

• Use caution in patients with pre-existing immunosuppression 1
• Safety during pregnancy remains unknown; antibodies are secreted in breast milk 1
• Long-term malignancy risk requires further study 1
• Temporary discontinuation recommended for febrile illness requiring antibiotics; restart after complete resolution 1

The selective IL-23p19 inhibitors (guselkumab, tildrakizumab, risankizumab) represent the most targeted approach, while ustekinumab provides broader IL-12/IL-23 blockade with established efficacy across multiple autoinflammatory conditions 2, 4, 9.