Novel biologic therapies in development targeting IL-12/IL-23.

Area of Science:

• Immunodermatology
• Psoriasis Pathogenesis
• Biologic Therapies

Background:

• Interleukin 12 (IL-12) and IL-23 play crucial roles in the immunopathogenesis of psoriasis.
• The shared p40 subunit of IL-12 and IL-23 presents a viable therapeutic target.

Purpose of the Study:

• To review clinical data on anti-IL-12/23 therapies for psoriasis.
• To evaluate the efficacy and safety of ustekinumab and ABT-874 in treating plaque psoriasis.

Main Methods:

• Analysis of Phase 3 clinical trial data (PHOENIX 1 and PHOENIX 2) for ustekinumab.
• Review of Phase 2 data for ABT-874.
• Assessment of PASI 75 response rates and safety profiles.

Main Results:

• Ustekinumab demonstrated significant benefits in moderate-to-severe plaque psoriasis, achieving PASI 75 response rates of 66% at week 12 and 85% at week 24.
• Treatment withdrawal led to psoriasis recurrence, while continued 12-weekly ustekinumab maintained response.
• Safety data up to 18 months showed a profile similar to placebo, with no major safety concerns identified.

Conclusions:

• Targeting the common p40 subunit of IL-12 and IL-23 is an effective therapeutic strategy for psoriasis.
• Ustekinumab is a well-tolerated and effective treatment for moderate-to-severe plaque psoriasis.
• ABT-874 also shows promise as an efficacious treatment option for plaque psoriasis.