The impact of ustekinumab on extraintestinal manifestations of Crohn's disease: A post hoc analysis of the UNITI studies

Neeraj Narula, Achuthan Aruljothy, Emily C L Wong, Ravi Homenauth, Abdul-Aziz Alshahrani, John K Marshall, Walter Reinisch, Neeraj Narula, Achuthan Aruljothy, Emily C L Wong, Ravi Homenauth, Abdul-Aziz Alshahrani, John K Marshall, Walter Reinisch

Abstract

This post hoc analysis of the UNITI studies found ustekinumab (UST) did not significantly improve overall extraintestinal manifestations (EIMs) of Crohn's disease compared to placebo-treated patients at weeks 6 and 52.

Background and aims: The UNITI trials demonstrated that UST was effective in inducing and maintaining clinical remission in Crohn's disease (CD). However, limited data exists regarding its effectiveness for treatment of EIMs. This post hoc analysis evaluated the efficacy of UST in treatment of EIMs.

Methods: Data from UNITI-1/2 and IM-UNITI (NCT01369329, NCT01369342, NCT01369355) were obtained from the Yale Open Data Access Project (2019-4104). Nine hundred and fourty-one patients eligible for UST induction and 263 patients eligible for maintenance UST were included. The primary outcome of interest was EIM resolution at Week 6 in UST and placebo-treated patients using the chi-square test. EIM resolution at Week 52 was also assessed. McNemar's test was used to compare the proportion of patients who reported active EIMs at weeks 6 and 52 versus baseline.

Results: From 941 UST-treated patients in UNITI-1/2, 504 had 527 EIMs at baseline. Overall, there was no significant difference in EIM resolution observed in UST-treated patients (186/504, 36.9%) compared to placebo (90/230, 39.1%; p = 0.564) at Week 6. Patients treated with continuous UST (91/119, 76.4%) had no significant difference in overall EIMs resolved at Week 52 compared to placebo (72/90, 80.0%; p = 0.542). Although many EIMs demonstrated reduction in prevalence compared to baseline at initiation of UST, only erythema nodosum was more likely to improve at Week 52 on treatment versus placebo.

Conclusion: Overall, UST did not lead to significant resolution of EIMs for CD compared to placebo at weeks 6 and 52.

Keywords: Crohn's disease; extraintestinal manifestations; resolution; ustekinumab.

Conflict of interest statement

Neeraj Narula holds a McMaster University Department of Medicine Internal Career Award. Neeraj Narula has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, and Ferring.

John K. Marshall has received honoraria from Janssen, AbbVie, Allergan, Amgen, Bristol‐Myers‐Squibb, Ferring, Fresenius Kabi, Janssen, Lilly, Lupin, Merck, Novartis, Paladin, Pfizer, Pharmascience, Procter & Gasmble, Roche, Shire, Takeda, and Teva.

Speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering‐Plough, Shire, Takeda, Therakos, Vifor, Yakult, Consultant for Abbott Laboratories, Abbvie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer‐Ingelheim, Bristol‐Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, OMass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering‐Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia, and 4SC, Advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer‐Ingelheim, Bristol‐Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering‐Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia, and 4SC.

No other authors have any relevant conflicts of interest.

No authors have received support for the submitted manuscript.

All authors approved the final version of the manuscript.

This study, carried out under YODA Project # 2019‐4104, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C.

© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.

Figures

FIGURE 1
FIGURE 1
Prevalence of extraintestinal manifestation at Week 6 in ustekinumab‐treated patients
FIGURE 2
FIGURE 2
Prevalence of extraintestinal manifestation at Week 52 in ustekinumab‐treated patients

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