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

United European Gastroenterol J. 2021 Jun;9(5):581-589. doi: 10.1002/ueg2.12094. Epub 2021 Jun 2.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Arthralgia / drug therapy
  • Arthralgia / etiology
  • Arthritis / drug therapy
  • Arthritis / etiology
  • Clinical Trials as Topic
  • Crohn Disease / complications*
  • Crohn Disease / drug therapy
  • Erythema Nodosum / drug therapy
  • Erythema Nodosum / etiology
  • Female
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Induction Chemotherapy
  • Iritis / drug therapy
  • Iritis / etiology
  • Maintenance Chemotherapy
  • Male
  • Pyoderma Gangrenosum / drug therapy
  • Pyoderma Gangrenosum / etiology
  • Ustekinumab / administration & dosage
  • Ustekinumab / therapeutic use*
  • Uveitis / drug therapy
  • Uveitis / etiology


  • Gastrointestinal Agents
  • Ustekinumab

Associated data