A randomised phase II study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate

Josef S Smolen, Sandeep K Agarwal, Elena Ilivanova, Xie Lillian Xu, Ye Miao, Yanli Zhuang, Ivo Nnane, Waldemar Radziszewski, Andrew Greenspan, Anna Beutler, Daniel Baker, Josef S Smolen, Sandeep K Agarwal, Elena Ilivanova, Xie Lillian Xu, Ye Miao, Yanli Zhuang, Ivo Nnane, Waldemar Radziszewski, Andrew Greenspan, Anna Beutler, Daniel Baker

Abstract

Objective: Interleukin (IL)-12 and IL-23 have been implicated in the pathogenesis of rheumatoid arthritis (RA). The safety and efficacy of ustekinumab, a human monoclonal anti-IL-12/23 p40 antibody, and guselkumab, a human monoclonal anti-IL-23 antibody, were evaluated in adults with active RA despite methotrexate (MTX) therapy.

Methods: Patients were randomly assigned (1:1:1:1:1) to receive placebo at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 12 weeks (n=55), guselkumab 50 mg at weeks 0, 4 and every 8 weeks (n=55), or guselkumab 200 mg at weeks 0, 4 and every 8 weeks (n=54) through week 28; all patients continued a stable dose of MTX (10-25 mg/week). The primary end point was the proportion of patients with at least a 20% improvement in the American College of Rheumatology criteria (ACR 20) at week 28. Safety was monitored through week 48.

Results: At week 28, there were no statistically significant differences in the proportions of patients achieving an ACR 20 response between the combined ustekinumab group (53.6%) or the combined guselkumab group (41.3%) compared with placebo (40.0%) (p=0.101 and p=0.877, respectively). Through week 48, the proportions of patients with at least one adverse event (AE) were comparable among the treatment groups. Infections were the most common type of AE.

Conclusions: Treatment with ustekinumab or guselkumab did not significantly reduce the signs and symptoms of RA. No new safety findings were observed with either treatment.

Trial registration number: NCT01645280.

Keywords: Disease Activity; Methotrexate; Rheumatoid Arthritis; Treatment.

Conflict of interest statement

Competing interests: JSS has received grants from AbbVie, BMS, Janssen, Lilly, MSD, Pfizer and Roche and has served as a consultant for AbbVie, Amgen, Astra-Zeneca, Astro, BMS, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi-Aventis and UCB. SKA served as a Steering Committee member for Janssen. EI served as a trial investigator for Janssen. XLX, YZ, IN, AG, and DB and YM are employees of Janssen Research & Development, LLC, and own stock in Johnson & Johnson, of which Janssen Research & Development, LLC, is a wholly owned subsidiary. AB and WR were employees of Janssen Research & Development, LLC, at the time this work was performed and own stock in Johnson & Johnson, of which Janssen Research & Development, LLC, is a wholly owned subsidiary. WR is currently employed at Sandoz, Inc., Princeton, NJ.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
Figure 1
Patient disposition through week 28. AE, adverse event; MTX, methotrexate.
Figure 2
Figure 2
Proportions of patients with an ACR20, ACR50 or ACR70 response at week 28. ACR20 response includes all randomised patients. ACR50 and ACR70 responses include patients who received ≥1 dose of study agent. ACR20/50/70, ≥20%/50%/70% improvement in the American College of Rheumatology criteria; MTX, methotrexate.
Figure 3
Figure 3
Mean Clinical Disease Activity Index (CDAI; panel A) and Simplified Disease Activity Index (SDAI; panel B) Scores through week 28. MTX, methotrexate.

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