Original article
Ixekizumab provides superior efficacy compared with ustekinumab over 52 weeks of treatment: Results from IXORA-S, a phase 3 study

https://doi.org/10.1016/j.jaad.2018.06.039Get rights and content

Background

Biologics targeting interleukin 17A (IL-17A) allow for rapid clearance of psoriatic plaques, with a clinically favorable safety profile.

Objectives

To compare the safety and efficacy of ixekizumab, an IL-17A antagonist, with the safety and efficacy of the IL-12/23 inhibitor ustekinumab through 52 weeks of treatment in the head-to-head trial IXORA-S.

Methods

Patients were randomized to ixekizumab (n = 136) or ustekinumab (n = 166) and dosed per the approved labels. After 1 year, efficacy was assessed via improvements in Psoriasis Area and Severity Index (PASI) score (with PASI 90 indicating a 90% or greater improvement from baseline PASI score) and a static Physician's Global Assessment (sPGA) response of either 0 or 0 or 1, with dropouts counted as nonresponders. Safety analyses included treatment-emergent adverse events (AEs).

Results

At week 52, significantly more ixekizumab-treated patients (P < .01) reported PASI 90 (104 [76.5%]), an sPGA response of 0 (72 [52.9%]), or an sPGA response of 0 or 1 (110 [82.1%]) responses than did ustekinumab-treated patients (PASI 90, 98 [59.0%]; sPGA response of 0, 60 [36.1%]; and sPGA response of 0 or 1, 108 [65.1%]). Treatment-emergent AEs, serious AEs, and discontinuation rates were not different between the treatment groups. Injection site reactions occurred more frequently in the ixekizumab-treated group (ixekizumab, 22 [16.3%]; ustekinumab, 2 [1.2%]) (P < .001).

Limitations

This study was not designed to compare safety end points related to rare events.

Conclusions

Compared with ustekinumab, ixekizumab showed superior efficacy and comparable safety outcomes through 52 weeks of treatment.

Section snippets

Study design and treatments

In this 52-week, phase 3b, double-blind, head-to-head trial (IXORA-S [NCT02561806]), eligible patients16 with moderate-to-severe plaque psoriasis were randomized 1:1 to receive subcutaneous injections of either ixekizumab or ustekinumab per the recommended dosing regimen (Fig 1).17, 18 Matching placebo injections were used to maintain blinding. The study methods were previously described in depth.16

Study population

Eligibility and exclusion criteria have been reported previously.16 Of note, eligible study

Study population

Of the 355 patients screened for IXORA-S (Fig 2), 302 were randomized to receive ustekinumab (n = 166) or ixekizumab (n = 136). The numbers of patients in both treatment groups who discontinued during the maintenance period were comparable, with 91% of patients completing the study through week 52 (151 of those who received ustekinumab [91.0%] and 124 of those who received ixekizumab [91.2%]). The most common reasons for discontinuation during the maintenance period were subject decision (8

Discussion

This 1-year analysis of the IXORA-S study shows that the superiority of ixekizumab over ustekinumab in patients with moderate-to-severe psoriasis was maintained through week 52. A PASI 90 response was sustained through 1 year by 76.5% of the ixekizumab-treated patients, and 52.2% had completely clear skin at week 52 (NRI analysis). When the NNT was considered, the superiority of treatment with ixekizumab over treatment with ustekinumab translated into 1 additional patient reaching PASI 90 for

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    Funding sources: Supported in full by Eli Lilly and Company, Indianapolis, Indiana. Dr Griffiths is a National Institute for Health Research senior investigator.

    Disclosure: Dr Paul has served as consultant and/or investigator for AbbVie, Amgen, Boehringer, Celgene, Eli Lilly and Company, Janssen, Leo, Novartis, and Pfizer. Dr Griffiths reports grants and personal fees from Eli Lilly and Company during the conduct of the study and grants and personal fees from AbbVie, Janssen, Celgene, Novartis, Pfizer, and GSK-Stiefel; grants from Sandoz, LEO Pharma, MMS, MSD, Sanofi, and Roche; personal fees from Amgen, UCB Pharma, Sun Pharmaceuticals, and MedScape; and, stock/stock options from CG Skin outside the submitted work. Dr van de Kerkhof has served as a consultant for Celgene, Centocor, Allmirall, Amgen, Pfizer, Philips, Abbott, Eli Lilly and Company, Galderma, Novartis, Jansen Cilag, Leo Pharma, Sandoz, and Mitsibishu and has worked as an investigator for Basilea, Pfizer, Eli Lilly and Company, Amgen, Abbvie, Philips Lighting, Jansen Cilag, and Leo Pharma. Dr Puig has been a clinical trial investigator for AbbVie, Amgen, GSK, Janssen, Eli Lilly and Company, MSD, Novartis, Pfizer, Regeneron, and VBL; he has also been a paid adviser/speaker for AbbVie, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, GSK, Janssen, Leo-Pharma, Eli Lilly and Company, Merck-Serono, MSD, Novartis, Pfizer, Regeneron, Sandoz, Sanofi, and VBL. Dr Dutronc, Dr Henneges, Dr Dossenbach, and Dr Hollister are employees of Eli Lilly and Company and receive a salary from and own stock in the company. Dr Reich has served as adviser and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo, Eli Lilly and Company, Medac, Merck Sharp & Dohme Corp, Novartis, Pfizer, Regeneron, Takeda, UCB Pharma, and Xenoport.

    Although the primary objective of this paper is to disclose efficacy and safety for IXORA-S at week 52, data for weeks 0 to 24 are provided for context. The data for weeks 0 to 24 data were previously published in the following article: Reich K, Pinter A, Lacour JP, et al. Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study. Br J Dermatol. 2017;177:1014-1023.

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    © 2018 Published by Elsevier on behalf of the American Academy of Dermatology, Inc.