SPIRIT-P2 results support ixekizumab for PsA patients with inadequate anti-TNF response
medwireNews: Phase III trial results presented at the Annual European Congress of Rheumatology (EULAR) 2017 and published in The Lancet suggest that the interleukin (IL)-17A inhibitor ixekizumab is a promising treatment option for patients with psoriatic arthritis (PsA).
“There is an unmet need for a number of patients who have either an inadequate response or are intolerant to treatment, or have a contraindication to a tumor necrosis factor (TNF) inhibitor; clearly, new treatment options are required,” study lead Peter Nash (University of Queensland, Brisbane, Australia) told delegates in Madrid, Spain.
In the SPIRIT-P2 trial, participants with active PsA who had a previous inadequate response to TNF inhibitors were randomly assigned to receive either ixekizumab 80 mg every 2 or 4 weeks after a starting dose of 160 mg, or placebo.
After 24 weeks of treatment, 48% of 123 participants receiving ixekizumab every 2 weeks and 53% of 122 patients receiving the drug every 4 weeks achieved at least a 20% improvement in ACR criteria (ACR20), compared with 19% of 118 patients receiving placebo, a significant difference.
Furthermore, change in Health Assessment Questionnaire-Disability Index scores from baseline and the proportion of patients with minimal disease activity were significantly higher at week 24 in both groups receiving ixekizumab compared with the placebo group, as was the proportion of patients achieving a Psoriasis Area and Severity Index score improvement of at least 75% at week 12.
Commenting on the study, Philip Mease (University of Washington School of Medicine, Seattle, USA) told medwireNews that before the SPIRIT-P2 trial began, “a slight increase in effectiveness with the [more frequent] dose” of ixekizumab was expected. However, he noted that the two doses were “pretty similar to each other.”
He added: “This gives us confidence that the monthly dosing will be ok even in a [TNF inhibitor inadequate response] population,” noting that the once monthly dose of ixekizumab is approved for the treatment of psoriasis after an initial 12-week period of treatment every 2 weeks.
When the ixekizumab-treated patients were stratified by their history of TNF use, a comparable proportion of participants achieved an ACR20 response at week 24 regardless of whether they had an inadequate response to one or two agents, or intolerance to TNF inhibitors.
In all, 73% of patients receiving ixekizumab every 2 weeks and 68% of those receiving the drug every 4 weeks experienced treatment-emergent adverse events over the study period, compared with 64% of participants in the placebo group. Serious adverse events were reported in 7%, 3%, and 3%, respectively.
The most common adverse events, occurring in at least 5% of participants in either ixekizumab group, were injection-site reaction, upper respiratory tract infection, nasopharyngitis, sinusitis, and oropharyngeal pain.
“There were no unexpected safety findings,” and the safety profile of ixekizumab therapy “was consistent with the overall profile” observed in previous studies, said Nash.
He emphasized that inflammatory bowel disease (IBD) did not occur as a result of ixekizumab treatment, and the two study participants with IBD at baseline did not experience flares.
Eight patients receiving ixekizumab experienced candida infection – two receiving the drug every 4 weeks and six receiving the drug every 2 weeks – compared with none in the placebo group.
Mease noted that candida was an “expected” side effect of ixekizumab treatment. “IL-17 inhibition helps protect the body from candida, so having mild-to-moderate oral thrush or vaginal candida is something we see in a small percentage of patients treated with IL-17 inhibitors. It is easy to treat or manage without having to stop the medication,” he explained.
Indeed, none of the patients in the SPIRIT-P2 study reported candida infection as a reason for treatment discontinuation.
Summing up the results, Mease said: “All in all, SPIRIT P2 teaches us that ixekizumab works well in a TNF inhibitor inadequate responding patient population.
“Realistically, when it is first released and used in patients, that is the population it will most likely be used in.”
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