Switching to infliximab after an inadequate response to etanercept was associated with a Physician Global Assessment score of clear or minimal in nearly two-thirds of patients with plaque psoriasis, based on results of a multicenter, open-label study.
This approach "offers an alternative therapeutic paradigm for patients with psoriasis who do not respond to initial treatment with a TNF [tumor necrosis factor]-alpha antagonist or those who lose response during anti-TNF-alpha treatment," the researchers wrote in a report that appeared online Dec. 8, 2011, in the Journal of the American Academy of Dermatology ( doi:10.1016/j.jaad.2011.10.020). "Additional studies are necessary to fully define the risks and benefits of transitions of this type for the treatment of psoriasis."
Dr. Alice B. Gottlieb
In an interview, lead study author Dr. Alice B. Gottlieb, professor and chair of dermatology at Tufts Medical Center, Boston, characterized the findings as important, "because many practitioners assume that if a patient does not respond to one TNF-alpha blocker – or if they have lost response to one TNF-alpha blocker – that another TNF-alpha blocker will not work. That’s just not true."
For the open-label study, known as PSUNRISE, Dr. Gottlieb and her associates at 49 centers in North America enrolled 215 adults with moderate to severe plaque psoriasis and an inadequate response to at least 4 months of treatment with etanercept (Enbrel). They were eligible for the trial if they had a Physician Global Assessment (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or without concomitant oral systemic methotrexate or cyclosporine at baseline and during the study. Treatment consisted of intravenous infusions of infliximab (Remicade) 5 mg/kg at baseline and weeks 2, 6, 14, and 22.
The study’s primary end point was the proportion of patients who achieved a PGA score of clear (0) or minimal (1) at week 10. Secondary end points included the proportion of patients who achieved a PGA score of 0 or 1 at week 26. Adverse events were documented through week 30.
Of the 215 patients, 36 withdrew consent or terminated their participation, one of whom returned at week 30. This left 179 patients who completed the study and 180 who completed the 30-week follow-up. The mean age of patients was 44 years, 64% were male, and 90% were white.
By week 10, 65% of patients achieved a PGA of 0 or 1, a score that was maintained in 61% of patients at week 26. Overall, 54% of patients had at least two grades of improvement in their PGA score.
In addition, mean Psoriasis Area and Severity Index scores decreased from 11.6 at baseline to 2.8 at week 10 and week 26, while Dermatology Life Quality Index scores of 0 or 1 were achieved by 44% of patients at week 10 and 41% of patients at week 26.
No unexpected side effects or safety concerns were reported. Eight patients (4%) had a serious adverse event; no cases of tuberculosis were observed. "Overall, the type and incidence of adverse events observed after switching from etanercept to infliximab in this study were similar to those reported in large, controlled trials of infliximab in patients with moderate to severe psoriasis," the researchers wrote.
They acknowledged certain limitations of their study, including data bias "and uncontrolled systematic errors, that are not present in a blinded, controlled randomized study. In addition, it would be easier to interpret the study results if a comparator group were included in the study design."
Dr. Gottlieb, who reported the first double-blind, placebo-controlled study of infliximab monotherapy in psoriasis ( Lancet 2001;357:1842-7 ), encouraged more dermatologists to add infliximab to their drug repertoire for severe psoriasis, "because it works in a high percentage of patients, it works quickly, and it can work when other TNF-alpha blockers don’t."
The study was supported by Janssen Biotech, which manufactures Remicade and is a subsidiary of Johnson & Johnson. Dr. Gottlieb disclosed that she has current consulting/advisory board agreements with several pharmaceutical companies, including Amgen and Pfizer, which market Enbrel, but not with Janssen Biotech. Two of the study authors, Dr. Marc Chevrier and Stephen Calabro, are employees of Janssen Biotech.