A drug in phase 3 trials has shown the ability to control long term psoriasis symptoms with as little as 4 shots a year. The double-blind, placebo-controlled Phase 3 study reports that 91% of patients responded to ustekinumab 90 mg maintenance therapy with at least a 75 percent improvement in psoriasis through one year.
Centocors Ustekinumab is a new monoclonal antibody in Phase 3 development for treating moderate to severe plaque psoriasis. The drug uses a unique biologic therapy targeting cytokines interleukin 12 (IL-12) and interleukin 23 (IL-23). IL-12 is an interleukin produced by dendrite cells[1], macrophages and human B-lymphoblastoid cell in response to antigens.
Due to its ability to stimulate immune responses and an anti-angiogenic action, there has been an interest in testing IL-12 as a possible anti-cancer drug. Previously, the cytokine IL-10 has been examined for its role in psoriasis as well[2]. Cytokines are naturally occurring proteins important for regulating the immune system; they are believed to play a role in immune-mediated inflammatory disorders.
“These findings show that ustekinumab may control plaque psoriasis with as few as four injections a year. We are encouraged by the results seen in clinical trials to date and the hope that ustekinumab may hold for patients and the dermatology community,"
said Dr. Kenneth Gordon, study lead and associate professor at Feinberg School of Medicine, Northwestern University, and Head of Dermatology, Evanston Northwestern Healthcare.
The Phase 3 efficacy and safety data for ustekinumab are extremely promising and offer hope to a patient population in need of additional therapeutic options," adds Kim Papp, MD, PhD, lead study investigator. It is estimated that approximately 7.5 million people in the United States and 10 million Europeans are living with psoriasis and nearly one-quarter of those people have cases that are considered moderate to severe.[3]
The study looked at the percentage of patients achieving at least a 75 percent improvement from baseline at week 12, as measured by the Psoriasis Area and Severity Index (PASI 75)[4]. At week 12, after two doses, 67 percent of patients receiving 45 mg ustekinumab and 66 percent of patients receiving 90 mg ustekinumab achieved PASI 75 compared with 3 percent of patients receiving placebo.
PHOENIX 1 Trials
PHOENIX 1 is a clinical trial which evaluated the efficacy and safety of ustekinumab in the treatment of 766 patients with chronic plaque psoriasis. Patients were randomized to receive subcutaneously administered ustekinumab or placebo. Patients randomized to receive ustekinumab received 45 mg or 90 mg doses at weeks 0 and 4 followed by the same dose every 12 weeks.
Patients in the placebo group crossed over to receive either 45 mg or 90 mg doses of ustekinumab at weeks 12 and 16 and every 12 weeks thereafter. The primary endpoint of the study was the proportion of patients achieving PASI 75 at week 12. Patients responding to ustekinumab through week 40 were randomized to either continue treatment with ustekinumab or were switched to placebo.
Through week 12 (the placebo-controlled portion of the study) the percentages of study participants experiencing at least one adverse event (AE) were comparable between the placebo group (48 percent) and the ustekinumab 45 mg group (57 percent) and 90 mg group (51 percent).
Those patients experiencing at least one serious AE were reported as follows: 1 percent and 2 percent of patients receiving 45 mg or 90 mg ustekinumab, respectively, compared with 2 percent of patients receiving placebo.
After the randomization at week 40, 46 percent and 49 percent of patients continuing treatment with 45 mg and 90 mg ustekinumab, respectively, experienced at least one AE, compared with 56 and 48 percent of patients switched to placebo. Serious AEs were observed in 0 and 1 percent of patients continuing treatment with 45 mg and 90 mg ustekinumab, compared with 0 and 2 percent of patients switched to placebo.
References
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Kaliski P, Hilkens CM, Snijders A, Snijdewint FG, Kapsenberg ML (1997). “IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells”. J. Immunol. 159 (1): 2835.
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K Asadullah, W Sterry, K Stephanek, D Jasulaitis, M Leupold, H Audring, H D Volk and W D D – IL-10 is a key cytokine in psoriasis J. Clin. Invest. 101(4): 783-794 (1998). doi:10.1172/JCI1476.
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National Psoriasis Foundation. About Psoriasis: Statistics.
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Alice B Gottlieb, Umesh Chaudhari, Daniel G Baker, Michelle Perate, Lisa T Dooley “The National Psoriasis Foundation Psoriasis Score System versus the Psoriasis Area Severity Index and Physician’s Global Assessment : a comparison – NPF-PS – PASI PGA Journal of Drugs in Dermatology, June, 2003