Ustekinumab shows superior efficacy in moderate-to-severe psoriasis
MedWire News: Ustekinumab appears to more effective than etanercept for the treatment of moderate-to-severe psoriasis, with a similar safety profile, say researchers.
“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,” Christopher Griffiths (University of Manchester, UK) and colleagues report.
The researchers randomly assigned 903 patients with moderate-to-severe psoriasis to receive subcutaneous injections of either 45 or 90 mg of ustekinumab (at weeks 0 and 4) or high-dose etanercept (50 mg twice weekly) for 12 weeks.
The average baseline Psoriasis Area and Severity Index (PASI) scores were 20.5 and 19.9 for patients receiving low and high doses of ustekinumab, respectively, and 18.6 for patients receiving etanercept.
After 12 weeks of treatment, 67.5% of patients receiving 45 mg of ustekinumab and 73.8% of those receiving 90 mg of the drug experienced at least a 75% improvement in PASI score, compared with 56.9% of etanercept-treated patients.
A 90% improvement was seen in a corresponding 36.4%, 44.7%, and 21.1% of patients.
A significantly greater proportion of patients taking ustekinumab had cleared or minimal disease, defined as a score of 0 or 1, respectively, on the physician’s global assessment score , at 65.1% of those receiving 45 mg and 70.6% of those receiving 90 mg, compared with 49.0% of patients receiving etanercept.
The onset of a response was also more rapid among patients taking ustekinumab compared with etanercept.
The researchers note in the New England Journal of Medicine that patients who did not respond to etanercept and were subsequently treated with ustekinumab generally had a good response. The median time to recurrence after stopping treatment was also longer following ustekinumab than etanercept, at 14.4 and 18.1 weeks with 45 mg and 90 mg, respectively, compared with just 7.3 weeks.
One or more adverse events occurred during treatment in 66.0% of patients who received 45 mg of ustekinumab and 69.2% of patients who received 90 mg of the drug, and in 70.0% of patients who receiving etanercept, with no significant difference between the two drug groups. Serious adverse events were seen in 1.9%, 1.2%, and 1.2%, respectively.
Griffiths and co-workers say that, as ustekinumab blocks interleukin (IL)-12 and IL-23, their findings provide additional evidence of the “central role of pro-inflammatory cytokines in psoriasis and suggest that agents targeting IL-12 and IL-23 provide effective treatment of psoriasis.”
They explain that, unlike tumor necrosis factor-α, which is produced by a wide range of immune and non-immune cells, IL-12 and IL-23 are produced primarily by antigen-presenting cells, including dermal dendritic cells, and serve to activate natural killer cells, CD8+ T cells, and CD4+ T cells, inducing the differentiation of CD4+ T cells into Th1 and Th17 cells.
“The activities of these cytokines affect many cell types… possibly providing communication between the immune system and the epidermis that results in the keratinocyte hyperplasia observed in psoriasis,” the researchers note.
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By Lucy Piper