Ixekizumab
Dr. Craig Leonardi
The second study assessed ixekizumab (LY2439821), a humanized IgG4 monoclonal antibody that neutralizes interleukin-17, in 142 patients with moderate to severe plaque psoriasis. The study patients were randomly assigned to receive subcutaneous injections of placebo or 10 mg, 25 mg, 75 mg, or 150 mg of ixekizumab at baseline and at 2, 4, 8, 12, and 16 weeks, reported Dr. Craig Leonardi of the department of dermatology, St. Louis University, and his associates.
The primary efficacy end point was the proportion of patients who achieved at least a 75% improvement in PASI score at 12 weeks. Significantly more patients at all ixekizumab doses except 10 mg achieved this benchmark (76.7%-82.8%), compared with placebo (7.7%).
In addition, significantly more patients (approximately 40%) in the higher-dose groups achieved a 100% improvement in PASI scores, indicating complete clearance of psoriasis, than in the placebo group. And significantly more patients receiving active treatment received physician’s global assessment scores of 0, indicating complete clearance, or 1, indicating minimal disease.
As with brodalumab, the beneficial effect of ixekizumab was evident as early as 1 week into treatment. The drug also significantly improved DLQI scores and decreased the severity of itching, Dr. Leonardi and his colleagues reported (New Engl. J. Med. 2012;366:1190-9).
Of note, ixekizumab was significantly more effective than placebo in patients who had psoriasis in difficult to treat areas such as the scalp and nails.
There were no serious adverse events. Two patients developed grade 2 neutropenia. Two patients showed elevations in liver enzymes that subsided when the drug was discontinued.
Both groups of investigators said their findings demonstrate that interleukin-17 is an appropriate target for psoriasis treatment. They also noted that the phase-II studies were too small and too brief to assess these agents’ effects on the risk of infection and cardiovascular events, and noted that further, longer-term studies of safety and efficacy are needed.
Even though there were few adverse effects in these two clinical trials and few patients withdrew from the studies, "a 12-week follow-up period is too short to assess the safety of treatments targeting interleukin-17," said Ari Waisman, Ph.D., in remarks taken from his editorial accompanying the reports on brodalumab and ixekizumab (N. Engl. J. Med. 2012;366:1251-2).
Despite the patients’ marked improvements with both brodalumab and ixekizumab, "future trials involving larger numbers of patients treated and followed for a much longer period of time will be needed," Dr. Waisman of the Institute for Molecular Medicine at Johannes-Gutenberg University of Mainz (Germany) said.
Dr. Papp’s study was funded by Amgen; Dr. Papp and his associates reported ties to numerous industry sources. Dr. Leonardi’s study was funded by Eli Lilly; Dr. Leonardi reported ties to Abbott, Amgen, Celgene, Centocor, Eli Lilly, Pfizer, Galderma, Incyte, Maruho, Schering-Plough, Sirtris, Stiefel, Novartis, Novo Nordisk, Vascular Biogenics, and Wyeth. Dr. Waisman reported ties to Teva, Phenex, and GlaxoSmithKline.