Toronto, ON, January 14, 2010 - Findings from an international, Phase 3 clinical study comparing the efficacy and safety of STELARA® (ustekinumab) with Enbrel† (etanercept) in the treatment of moderate to severe plaque psoriasis showed a significantly higher clinical response with both doses of STELARA® than etanercept over a 12-week period. The first-of-its-kind head-to-head study comparing two biologic agents for plaque psoriasis also shows the efficacy of STELARA® among patients in the study who failed to respond to etanercept. The international study included 18 Canadian sites. Findings from this study have been published in the January issue of The New England Journal of Medicine.
Psoriasis is an inflammatory disorder characterized by raised, inflamed, red lesions, or plaques, which can cause physical pain. It is estimated that approximately one million Canadian adults1 and nearly three per cent of the world's population are living with psoriasis, which can present in various forms, ranging from mild to severe and disabling. Nearly one-quarter of people with psoriasis have cases that are considered moderate to severe.2 Plaque psoriasis is the most common form of psoriasis, affecting approximately 80 per cent of those suffering from this condition.3
"Over the course of the 12 week comparison study, patients with moderate to severe plaque psoriasis were to receive two injections of STELARA® or 24 injections of etanercept. A substantial proportion of patients achieved high levels of skin clearance with STELARA® at the study's primary endpoint at week 12 and following crossover from etanercept. Those crossing over from etanercept, patients who showed a lack of response to etanercept during 12 weeks of treatment, generally responded very well to STELARA," said Dr. Kim Papp, dermatologist and study investigator. "Treatment convenience is an important factor in the management of psoriasis as it can lead to greater compliance. The high level of efficacy observed in this study with an infrequent dosing schedule of STELARA® is encouraging as we have a new, effective, and convenient treatment of moderate to severe plaque psoriasis."
In the comparator study, 68 and 74 per cent of patients receiving subcutaneous injections of STELARA® (45 mg or 90 mg) at weeks zero and four achieved at least a 75 per cent reduction in psoriasis as measured by the Psoriasis Area and Severity Index (PASI 75) at week 12, the primary endpoint, compared with 57 per cent of patients receiving subcutaneous injections of 50 mg etanercept twice per week for 12 weeks (P = 0.01 for STELARA® 45 mg; P < 0.001 for STELARA® 90 mg, each compared with etanercept). Onset of clinical response appeared more rapidly among STELARA®-treated patients, with higher numbers of patients achieving PASI 75 by week eight compared with patients receiving etanercept.
Investigators also reported that a greater proportion of patients receiving STELARA® achieved a marked improvement in psoriasis as assessed by PASI 90 response, or nearly complete clearance of psoriasis. At week 12, 36 per cent of patients receiving STELARA® 45 mg and 45 per cent of patients receiving STELARA® 90 mg achieved PASI 90 compared with 23 per cent of patients receiving etanercept (P < 0.001 for each comparison versus etanercept). Moreover, a greater proportion of patients in the STELARA® 45 mg and 90 mg treatment groups achieved a Physician Global Assessment (PGA) score of "cleared" or "minimal" (65 per cent and 71 per cent, respectively) compared with patients in the etanercept treatment group (49 per cent) [P < 0.001 for each comparison versus etanercept].
Patients who had an inadequate response to etanercept, as measured by PGA score (classified as moderate, marked or severe psoriasis at week 12) received two injections of STELARA® 90 mg at weeks 16 and 20. At week 28, investigators reported that 49 and 23 per cent of patients who failed to respond to etanercept and who crossed over to STELARA® achieved PASI 75 and PASI 90, respectively.
In addition, patients classified as responders (having a PGA score of cleared, minimal or mild) at week 12, discontinued therapy until recurrence of psoriasis (PGA of moderate or greater). In these patients, the median length of time to disease recurrence was longer for STELARA® patients (14.4 and 18.1 weeks for 45 and 90 mg, respectively) than etanercept patients (7.3 weeks). Response was regained in 84 per cent of patients following retreatment with two STELARA® (45mg or 90 mg) injections.
Through week 12 of the study, the percentages of study participants experiencing at least one adverse event (AE) were comparable between the STELARA® 45 mg group (66 percent), the STELARA® 90 mg group (69 percent) and the etanercept 50 mg group (70 percent). Those patients experiencing at least one serious AE through week 12 were reported as follows: 1.9 percent and 1.2 percent of patients receiving STELARA® 45 mg or 90 mg, respectively, compared with 1.2 percent of patients receiving etanercept. Rates of specific AEs were generally comparable between treatment groups with the exception of injection site reactions, which were reported in 25 percent of patients treated with etanercept versus 4.3 percent and 3.7 percent with STELARA® 45 mg and 90 mg, respectively, though this disparity may have been influenced by the greater number of etanercept injections administered (at least 24 in the 12-week portion of the study) compared with two STELARA® injections.
Through week 64, AEs were generally comparable between patients in the 45 mg (87 percent) and 90 mg (89 percent) STELARA® groups. In patients who crossed over from etanercept to ustekinumab, generally similar proportions experienced AEs (79 percent versus 65 percent) and serious AEs (3.5 percent versus 3.4 percent) before versus after transitioning to STELARA®.
About the ACCEPT Trial
The Phase 3, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Ustekinumab Compared to Etanercept in the Treatment of Subjects with Moderate to Severe Plaque Psoriasis (ACCEPT) included 903 patients with chronic plaque psoriasis (etanercept=347, STELARA® 45 mg=209, STELARA® 90 mg=347). Patients were randomized to receive subcutaneously administered STELARA or etanercept. Patients randomized to receive STELARA® received 45 mg or 90 mg doses at weeks zero and four. Patients in the etanercept group received twice-weekly doses of 50 mg for 12 weeks. The primary endpoint of the study was the proportion of patients who achieved PASI 75 at week 12. At week 12, patients in the etanercept group who were classified as non-responders (i.e., had moderate, marked or severe psoriasis) received 90 mg of STELARA® at weeks 16 and 20. STELARA® non-responders received one additional dose of STELARA® at week 16. Treatment was interrupted for all patients who had cleared, minimal or mild psoriasis at the end of week 12, and all patients were retreated with 45 or 90 mg STELARA® when their disease worsened to moderate or worse.
Psoriasis is an immune mediated skin disease in adults and one of the oldest skin conditions known to man.4 The symptoms of psoriasis usually appear between the ages of 15 and 35 with 75 per cent of people developing it before the age of 40.5
The severity of psoriasis can have a profound impact on a patient's quality of life. Even mild psoriasis can undermine self esteem and disturb personal relationships. For some individuals, reduction in physical and mental functioning may be similar to the distress caused by other chronic diseases such as cancer, heart disease, diabetes and hypertension.6
Plaque psoriasis is the most common form and affects approximately 80 per cent of those suffering from the condition7. It usually results in painful, itchy, sore patches of thick, red or inflamed skin covered with silvery scales known as plaques. Plaques can occur anywhere on the body - most commonly on the elbows, knees, lower back and the area around the bellybutton. Severity ranges from minor localized patches to complete body coverage.
About STELARA® (ustekinumab)
STELARA® is a first-in-class, human, monoclonal antibody approved first in the world by Health Canada in December 2008 for the treatment of psoriasis. A selective immunomodulating agent, STELARA® is indicated for the treatment of adult patients with chronic moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.8
STELARA® works by targeting and regulating the activity of cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23)9. These cytokines are naturally occurring proteins that are important in regulating immune responses, and are thought to be associated with immune-mediated inflammatory disorders, including plaque psoriasis.10
Centocor Ortho Biotech Inc. discovered STELARA® and has exclusive marketing rights to the product in the United States. Janssen-Ortho Inc. has exclusive marketing rights in Canada for the treatment of moderate-to-severe plaque psoriasis.
About Janssen-Ortho Inc.
Janssen-Ortho Inc. is a healthcare company committed to providing Canadians with innovative treatment options that enhance and improve life. Headquartered in Toronto, the company offers a broad range of medications used in psychiatry, dementia, attention deficit hyperactivity disorder, psoriasis, pain management, women's health, infectious disease, anemia, oncology, and virology.
For more information, please contact:
1Canadian Skin Patient Alliance web site: http://www.skinpatientalliance.ca/en/skin-conditions-diseases/psoriasis
2National Psoriasis Foundation, About Psoriasis Available at http://www.psoriasis.org/about/stats/.
3American Academy of Dermatology web site http://www.aad.org/media/background/factsheets/fact_psoriasis.html.
4Psoriasis Society of Canada. Available at http://www.psoriasissociety.org/education.htm
5Skin Care Physicians. What is Psoriasis? Available at: www.skincarephysicians.com/psoriasisnet/whatis.html
6Canadian Skin Patient Alliance web site. Available at: http://www.skinpatientalliance.ca/en/skin-conditions-diseases/psoriasis/impacts-quality-life
7National Psoriasis Foundation. About Psoriasis. Available at http://www.psoriasis.org/about/psoriasis/plaque.php
8STELARA product monograph - December 12th, 2008.
9STELARA product monograph - December 12th, 2008.
10Kikly K, Liu L, Na S, Sedgwick J. The IL-23TH (17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol. 2006;18:670-675