BOSTON -- A second major presentation here at the American College of Rheumatology annual meeting suggested that secukinumab may be useful for conditions beyond its FDA-approved indication of psoriasis.
In a late-breaking session, secukinumab was shown to be effective for active psoriatic arthritis, reported Iain B. McInnes, MD, of the University of Glasgow in Scotland.
Earlier at the meeting, other researchers reported on the effects of this human anti-interleukin (IL)-17A monoclonal antibody in ankylosing spondylitis.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
McInnes and colleagues reported that significantly greater numbers of 20% improvement responses on the criteria of the American College of Rheumatology (ACR20) were seen among patients given secukinumab compared with placebo (54% and 51% versus 15.3%, P<0.0001 for both).
Secukinumab was approved just weeks ago for psoriasis based on pivotal studies that showed reductions of 75% in the Psoriasis Area and Severity Index (PASI75) of 67% to 82% compared with only 4% to 5% with placebo.
There are several reasons why this monoclonal antibody is plausible for use in psoriatic arthritis, McInnes explained. IL-17A has been implicated in the pathogenesis of the disease, and polymorphisms in genes involved in IL-17A signaling have been shown to increase disease susceptibility.
In addition, high levels of cells that produce these cytokines have been detected in the skin and joints of patients with psoriatic arthritis.
To further explore the effects of this agent on psoriatic arthritis, McInnes and colleagues conducted a phase III, 24-week randomized trial in which 397 adults were given secukinumab in doses of 300, 150, or 75 mg or placebo once weekly for the first month and then once monthly.
Patients' mean age was 47, and the gender distribution was about equal.
At baseline, half of patients had Psoriasis Area and Severity Index (PASI) scores above 10. Almost 40% had dactylitis present and almost 60% had enthesitis.
A total of 35% of the patients had previously been nonresponders to antitumor necrosis factor (TNF) therapy.
By week 3, improvements were already being seen for the two higher doses of secukinumab.
Among patients who were anti-TNF nonresponders, response rates for the 300- and 150-mg groups were 45.5% and 29.7% compared with 14.3% for the placebo group (P<0.05 for 300 mg), while among those who were anti-TNF naive, rates were 58.2% and 63.5% versus 15.9% (P<0.05 for both).
"Responses were particularly robust among the TNF-naive patients," McInnes said.
More stringent ACR50 and 70 criteria also were greater in the secukinumab 300- and 150-mg groups than in the placebo group, with ACR50s being seen in 35% of both dose groups compared with 7.1% of the placebo group, and ACR70s being seen in 20% and 21% versus 1%.
Half of the patients were on concomitant methotrexate, and ACR20 responses were seen in 54.5% and 53.6% of those also receiving methotrexate and those not on the background therapy.
Skin responses, as measured on the PASI75 and PASI90, also significantly favored secukinumab. PASI75 responses were seen in 63.4% of the 300-mg group and 48.3% of the 150-mg group compared with 16.3% of the placebo group (P<0.0001 and P<0.01), while PASI90s were seen in 48.8% and 32.8% compared with 9.3% (P<0.001 and P<0.01, respectively).
The rates of resolution of dactylitis and enthesis also were greater with secukinumab compared with placebo (56.5% and 50% versus 14.8%, and 48.2% and 42.2% versus 22.5%, P<0.05 for both).
Significant improvements also were seen in quality of life and physical functioning measures.
Adverse events were similar in the active treatment and placebo groups, at 53.8% of patients in all the secukinumab groups and 58.2% in the placebo group, while serious adverse events were reported in 3.3% and 2%, respectively.
An adverse event of special interest was Candida infections, because IL-17 has been implicated in fungal immune responses. There were five cases of candidiasis, but all were mild or moderate and resolved with treatment.
Both doses of secukinumab showed rapid and "clinically significant" improvements in the signs and symptoms of psoriatic arthritis, McInnes said.
Disclosures
The study was sponsored by Novartis.
McInnes disclosed relevant relationships with Pfizer, UC, Bristol-Myers Squibb (BMS), Novartis, Amgen, Janssen, AbbVie, Celgene, and Eli Lilly.
Co-authors disclosed relevant relationships with AbbVie, Amgen, Biogen Idec, BMS, MSD, Celgene, Crescendo, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Vertex, Covagen, Roche, AstraZeneca, Augurex, Centocor, Chugai, Daiichi, Galapagos, GlaxoSmithKline, Novo Nordisk, Otsuka, sanofi-aventis, Schering-Plough, and Wyeth.
Primary Source
American College of Rheumatology
Source Reference: McInnes, IB, et al "Secukinumab, a human anti-interleukin-17A monoclonal antibody, improves active psoriatic arthritis: 24-week efficacy and safety data from a phase 3 randomized, multicenter, double-blind, placebo-controlled study using subcutaneous dosing" ACR 2014; Abstract L1.