Ustekinumab at a dose of 45 or 90 mg at baseline and again at week 4 was more effective than a 50-mg dose of etanercept twice weekly in a 12-week randomized study of patients with moderate-to-severe psoriasis.
The findings "are generally consistent with those of previous studies," researchers led by Dr. Christopher E.M. Griffiths reported in the Jan. 14 issue of the New England Journal of Medicine. "The high level of efficacy of ustekinumab treatment that we observed was achieved with only two injections during the 12-week period, as compared with twice-weekly injections of etanercept, which may be important for improved treatment compliance."
For this phase III study, known as the Active Comparator (CNTO 1275/Enbrel) Psoriasis Trial (ACCEPT), 903 patients with moderate-to-severe arthritis were randomly assigned to one of three treatment groups: 45 mg ustekinumab at baseline and week 4 (209 patients), 90 mg of ustekinumab at baseline and week 4 (347 patients), or 50 mg etanercept twice weekly for 12 weeks (347 patients).
Ustekinumab (marketed as Stelara by Centocor Ortho Biotech Services) blocks interleukin-12 and interleukin-23 while etanercept (marketed as Enbrel by Amgen and Wyeth) blocks tumor necrosis factor (TNF)-alpha.
The primary end point was the proportion of patients who achieved at least 75% improvement in the Psoriasis Area and Severity Index (PASI) at week 12. A secondary end point was the proportion of patients with cleared or minimal disease according to the physician's global assessment score (N. Engl. J. Med. 2010;362:1,118-28).
A total of 68% of patients in the 45-mg ustekinumab arm and 74% of those in the 90-mg ustekinumab arm achieved at least a 75% in the PASI score at week 12, compared with 57% of those in the etanercept arm.
Similarly, 65% of patients in the 45-mg ustekinumab arm and 71% of those in the 90-mg ustekinumab arm had cleared or minimal disease based on the physician's global assessment score, compared with 49% of those in the etanercept arm.
As for safety, the proportion of patients who had at least one adverse event during the study was similar between groups (66% in the 45-mg ustekinumab arm, 69% of patients in the 90-mg ustekinumab arm, and 70% in the etanercept arm).
Dr. Griffith of the Manchester (England) Academic Health Science Centre and his associates wrote that the study findings "could have implications for determining the optimal approach to the treatment of psoriasis and, in particular, the need for therapeutic strategies targeting Th1 cells, Th17 cells, or both to provide optimal benefit and safety."
The study was supported by Centocor Research and Development.
The investigators disclosed conflicts with a number of pharmaceutical companies, including Centocor, Amgen, and Wyeth.
Dr. Andrew Blauvelt, professor of dermatology and molecular microbiology & immunology at Oregon Health and Science University, Portland, spoke about this trial in an interview. "This is the first study to directly compare two biologic agents head-to-head for the treatment of moderate-to-severe psoriasis. This kind of direct comparison has been greatly needed in the psoriasis field. Until this point, we have been assuming that ustekinumab was better than etanercept for patients with moderate-to-severe psoriasis based upon individual clinical trials. Even though people had a hunch that etanercept would not perform as well as ustekinumab, this study now provides proof of that assumption.
The overall findings are not surprising at all. The treatment response rates for both agents are similar to the numbers that have been reported in previous clinical trials of each individual agent.
It's hard to say what the direct impact of this particular clinical trial will be. In situations where insurance companies have a tiered approval process whereby etanercept failure is a condition for ustekinumab use, this study is unlikely to change that requirement. For insurance companies that do not have a tiered approval process, this study could logically lead to treatment guidelines that support initial use of ustekinumab, without requiring prior use of etanercept.
Taking into consideration whether a patient has psoriatic arthritis or not should also be determined before making the decision between etanercept and ustekinumab, because etanercept is approved for psoriatic arthritis and ustekinumab is not.
Clinicians who provide care to patients with moderate-to-severe psoriasis have cautious optimism for ustekinumab in terms of its long-term safety profile. However, we really don't know for sure what that long-term safety profile is going to be. Accordingly, some of my colleagues will argue for the use of etanercept over ustekinumab from a safety point of view until more is known about ustekinumab's long-term effects."
Dr. Blauvent is also the psoriasis research director of OHSU's Center of Excellence for Psoriasis and Psoriatic Arthritis. He is an investigator for an earlier ustekinumab trial (PHOENIX 2). He has previously acted as a scientific advisor for Amgen Wyeth and Centocor, but was not involved with ACCEPT.