Infliximab Reduces Psoriasis Activity in Etanercept-Resistant Patients
By Deborah Brauser
Medscape Medical News
March 9, 2010 (Miami Beach, Florida) — Patients with mild to severe plaque psoriasis who switched to infliximab (Remicade, Centocor Ortho Biotech) after a poor response to etanercept (Enbrel, Amgen and Wyeth) therapy showed a reduction in disease activity, according to results from the new PSUNRISE study presented here at the American Academy of Dermatology 68th Annual Meeting.
"The purpose of this study was to see if patients who had failed one [tumor necrosis factor] TNF-blocker, etanercept, [could be rescued] with a second TNF-blocker, infliximab," said lead author Alice Gottlieb, MD, PhD, chief and chair of the dermatology department at Tufts Medical Center and Tufts University School of Medicine in Boston, Massachusetts.
"That's important because psoriasis patients have their disease generally from a young age through the rest of their lives," she reported. "Although TNF is a very good target, not everybody responds optimally to [a TNF blocker], or they lose responsiveness to one. So over a patient's lifetime, you need multiple TNF blockers to give them a choice."
She noted that this wasn't a comparison trial. "Both etanercept and infliximab are good drugs. This study wasn't about that."
Disease Activity, Quality of Life Measured
The investigators enrolled 215 patients over the age of 18 (63.7% male; mean age, 44.4 years) with "significant disease activity" (defined as a static Physician Global Assessment [PGA] score of 2 or higher) who had previously received etanercept 25?mg twice weekly or 50?mg once or twice a week, alone or with methotrexate or cyclosporine, for a minimum of 4 months, with an inadequate treatment response. These patients began receiving 5?mg/kg infusions of infliximab 2 weeks after taking their last dose of etanercept (week?0); infusions were repeated at weeks 2, 6, 14, and 22.
Efficacy evaluations were performed at all time points through to week?26, and the primary end point was the percent of patients achieving PGA scores of 1 or below at week?10. The median PGA at baseline was 2.8.
Secondary end points included analyses of body surface area (BSA), Psoriasis Area and Severity Index (PASI) scores and responses, health-related quality-of-life measures, and psoriasis assessments. Safety evaluations were given through to week?30.
In addition, "a protocol-stipulated interim analysis for safety was performed when the first 105 patients completed week?10, which has been previously reported," explained Dr. Gottlieb.
Fast, Durable Response With Infliximab
At week?10, a total of 65.4% of the patients treated with infliximab had a PGA of clear (score of 0) or mild (score of 1). At week?26, this number increased to 72.4%. PASI?75 responses at weeks?10 and 26 were 51.7% and 54.5%, respectively.
"The majority of the PGA responders exhibited this response within 6 weeks of treatment initiation," reported Dr. Gottlieb. "So not only did we rescue 65% of them, we rescued them relatively quickly."
In addition, "substantial improvements in mean BSA and mean [Dermatology Life Quality Index] DLQI were observed throughout the study," reported Dr. Gottlieb. "The proportion of patients achieving a DLQI of 1 or less was 44% at week?10 and 41% at week?26."
Of the 215 patients who received infliximab treatment, 5.6% had infusion reactions and 68.8% had at least 1 adverse event. However, only 3.7% experienced 1 or more serious adverse events.
"There was a similar safety profile to what you normally see with infliximab. Infection adverse events were primarily related to respiratory tract complaints and cutaneous infections," explained Dr. Gottlieb.
When asked why clinicians shouldn't just start treatment with infliximab, Dr. Gottlieb said that although she believes it gives the best response, "it is given by [intravenous] infusion, which is not for everyone."
"In summary, one can take etanercept nonresponders and rescue two thirds of them with infliximab and the response is quick. Plus, the safety profile is to be expected," she concluded.
Outside Quotes
"This study was interesting," said Alan Menter, MD, chair of psoriasis research at Baylor Research Institute in Dallas, Texas, and founder of the International Psoriasis Group.
"All the companies are now looking to see, when a patient has failed 1 of the treatments, [whether they are] more likely to fail another treatment in the same class. That is what this research looked at," said Dr. Menter, who was not involved with the study.
"They took those patients who did not do well on [etanercept] and put them on a drug with a similar action, even though it was a different antibody, [and found] that over 64% did respond. It isn't a class effect of TNF [receptor] that if you fail 1 you're going to fail them all."
He noted that "we're going to see more of these types of studies," especially with the new [interleukin]12/23 drugs, such as ustekinumab.
This study was sponsored by Centocor Ortho Biotech Services. Dr. Gottlieb reports sitting on the advisory boards for "many psoriasis-interested parties." Dr. Menter reports doing studies for many of the companies involved with psoriasis therapies.
American Academy of Dermatology (AAD) 68th Annual Meeting: Abstract?P3341. Presented March?7, 2010.
