Original article
A 52-week, open-label study of the efficacy and safety of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with chronic plaque psoriasis

Data from this manuscript were presented at the 22nd Congress of the European Academy of Dermatology and Venereology, Istanbul, Turkey, October 2-6, 2013; and at the 72nd Annual Meeting of the American Academy of Dermatology, Denver, Colorado, March 21-25, 2014.
https://doi.org/10.1016/j.jaad.2014.07.048Get rights and content

Background

Patients with moderate to severe plaque psoriasis demonstrated positive responses to ixekizumab, an anti-interleukin-17A monoclonal antibody, in a phase-II, randomized, placebo-controlled trial.

Objective

We sought to evaluate long-term efficacy and safety of ixekizumab.

Methods

After receiving 10, 25, 75, or 150 mg of ixekizumab or placebo during randomized, placebo-controlled trial, patients with less than 75% improvement from baseline on the Psoriasis Area and Severity Index (PASI) score (PASI75) entered open-label extension (OLE); patients with PASI75 or higher entered a treatment-free period (weeks 20-32), then entered OLE after meeting response criteria. During OLE, patients received 120 mg of subcutaneous ixekizumab every 4 weeks.

Results

In all, 120 patients entered OLE; 103 completed 52 weeks or more of treatment. Overall, 77% of patients achieved PASI75 at week 52 (nonresponder imputation). Patients who responded to treatment in the randomized, placebo-controlled trial maintained a high-level response by week 52 of OLE (PASI75 = 95%; 90% improvement from baseline on the PASI score = 94%; 100% improvement from baseline on the PASI score = 82%). Irrespective of dose in the randomized, placebo-controlled trial, each group had similar response rates at week 52 of OLE. The exposure-adjusted incidence rate for adverse events was 0.47 and for serious adverse events was 0.06 per patient-year during OLE.

Limitations

No control group, small sample sizes, and bias toward retention of patients with positive responses limit interpretation.

Conclusion

A high proportion of patients responded to ixekizumab therapy and maintained clinical responses over 1 year of treatment with no unexpected safety signals.

Section snippets

Study design and treatment

This was a multicenter, OLE study of a phase-II RCT designed to evaluate the long-term use of ixekizumab in patients with chronic (≥6 months) moderate to severe plaque psoriasis. Patients were administered ixekizumab (10, 25, 75, or 150 mg) or placebo subcutaneously at 0, 2, 4, 8, 12, and 16 weeks in the RCT, the results of which have been previously published.6 Patients who completed 20 weeks of the RCT and who had not experienced a treatment-related adverse event (AE) or a serious AE (SAE)

Patient disposition and baseline characteristics

Of the 129 patients who completed the RCT, 120 (93%) entered the OLE and received at least 1 dose of study drug and 103 (86%) completed at least 52 weeks of treatment (Fig 1). On average, patients were 47 years of age; 58% were men, 93% were Caucasian, and the majority (93%) had previously received treatment for psoriasis.

Before entering the OLE, 69 of 120 (58%) patients (10 mg, n = 5; 25 mg, n = 20; 75 mg, n = 21; 150 mg, n = 23) had achieved a PASI75 response at week 20 of the RCT and entered

Discussion

In this long-term OLE study of ixekizumab for the treatment of moderate to severe plaque psoriasis, a high rate of clinical response was observed in all patient groups. There was a low rate of discontinuation over 52 weeks, and 77% (92 of 120) of patients who entered the OLE achieved a PASI75 response. Patients who had taken subtherapeutic doses (10 mg or 25 mg) during the RCT achieved PASI75, PASI90, and PASI100 response rates that were similar to higher-dose groups by week 52. The majority of

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Supported by Eli Lilly and Company.

Disclosure: Dr Gordon is a consultant and/or investigator for AbbVie Inc, Amgen Inc, Centocor, Merck, Eli Lilly and Company, Novartis, and Pfizer. Dr Leonardi is a consultant and/or investigator for AbbVie Inc, Amgen Inc, Celgene Corp, Centocor, Eli Lilly and Company, Galderma, Genentech, Genzyme, GlaxoSmithKline, Incyte, Novartis, Novo Nordisk, Pfizer, Schering-Plough, Sirtris, Stiefel, Vascular Biogenics, and Wyeth, and is a speaker for AbbVie Inc. Dr Lebwohl has been a consultant and/or investigator for Inbios, Coronado Biosciences, AbbVie Inc, Valeant, Taro, Pfizer, UCB Pharma, Forward Pharma, DermiPsor, Galderma, Ranbaxy, Novartis, Dermira, Merz, Merck, LEO Pharma Inc, Janssen-Biotech, GlaxoSmithKline, Eli Lilly and Company, Celgene Corp, Can-Fite Biopharma Ltd, Anacor Pharmaceuticals Inc, and Amgen Inc. Dr Blauvelt is a consultant and/or investigator for AbbVie Inc, Amgen Inc, Boehringer Ingelheim, Celgene Corp, Janssen Biotech, Merck, Novartis, Pfizer, and Eli Lilly and Company. Drs Cameron, Braun, Erickson, and Heffernan are employees and shareholders of Eli Lilly and Company.

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