Interleukin (IL)-23 is an important regulator of T helper-17 lymphocytes, which influence the cutaneous immune system by production of
IL-17 and several other proinflammatory
cytokines. This pathway has been recently linked to the pathogenesis of
psoriasis and numerous other
skin diseases. A newly developed
biologic drug,
ustekinumab (CNTO-1275), which targets the p40 subunit of
IL-12 and
IL-23, was approved by the US FDA and the European Medicines Agency in 2009 for the treatment of moderate to severe
psoriasis. Administered as
subcutaneous injections of 45 mg at weeks 0 and 4, and then every 12 weeks,
ustekinumab produces a 75% improvement in the
Psoriasis Area and Severity Index (PASI) in 66.4-75.7% of patients and a Dermatology Life Quality Index (DLQI) score of 0 or 1 in 55-56% of patients after 12 weeks of
therapy. A recent clinical trial also indicates the possible efficacy of
ustekinumab in
psoriatic arthritis. The proportion of patients who had at least one adverse event through 12 weeks in clinical studies was 51.6-57.6% in the
ustekinumab group and 50.4% in the placebo group. Serious adverse events were observed in 1.4-1.6% of patients treated with
ustekinumab and in 1.4% of patients receiving placebo.
Injection-site reactions occurred in 1-2% of patients and 5% of patients developed anti-
ustekinumab antibodies. Further studies are needed to evaluate the long-term efficacy and safety of
ustekinumab. Another
biologic drug that targets the same molecules,
briakinumab (ABT-874), has recently had its approval application withdrawn in the US and Europe to conduct further analysis and clinical trials. The company plans resubmission at a later date. Other
IL-23 pathway inhibitors in the pipeline include anti-p19
monoclonal antibody and
apilimod (STA-5326), which interfere with
IL-23 activity, as well as
secukinumab (AIN-457),
LY-2439821, and
AMG-827, which exhibit their activity at other targets of the
IL-23 pathway.