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

Abstract

Summary 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.

Effectiveness of Third-Class Biologic Treatment in Crohn’s Disease: A Multi-Center Retrospective Cohort Study

“…In our study, concomitant immunomodulatory therapy was not associated with the likelihood of response or remission, in similarity with the recently published data [45,46]; nonetheless, the risk of treatment discontinuation was higher in patients on monotherapy. The effect of concomitant immunomodulators in the present study could be explained by a decrease in the risk of anti-drug antibody formation in line with the recently reported data on sequential anti-TNF use [47] or due to an additional anti-inflammatory effect [48,49]. Another somewhat surprising finding was the lack of association of the number of previously used anti-TNFs with therapeutic outcomes.…”

Joint Disease Activity in Inflammatory Bowel Disease–associated Peripheral Spondyloarthritis Stratifies Therapeutic Response

“… 8 Post hoc analysis of the UNITI-1/2 and IM-UNITI cohorts revealed no impact of UST on arthritis or arthralgia at week 6 or week 52 compared with placebo. 9 Consistent with these findings, our data show that although UST and anti-TNF α induced equivalent rates of clinical response of intestinal disease, UST did not significantly improve systemic joint symptoms using validated SpA disease activity indexes.…”

UEG week and UEG journal: A strong scientific liaison

“…In a post‐hoc analysis of 3 clinical trials (NITI‐1, UNITI‐2, and IM‐UNITI) investigating UST in patients with moderate to severe Crohn's disease (CD), Narula et al evaluated efficacy of UST for treatment of EIM. 20 Notably, the overall rate of EIM resolution was comparable between UST and placebo at week 6 (36.9% vs. 39.1%) and 52 (76.4% vs. 80%); in the sub‐analysis evaluating the efficacy of UST according to the type of EIM, only erythema nodosum was significantly improved at week 52 of treatment. Awaiting confirmation by controlled studies using validated techniques with assessments performed by trained physicians, these data indicate that UST is not effective for the treatment of EIM in CD.…”

“…Yet, studies are limited due to retrospective design, small sample size, and lack of control groups. In a post‐hoc analysis of 3 clinical trials (NITI‐1, UNITI‐2, and IM‐UNITI) investigating UST in patients with moderate to severe Crohn's disease (CD), Narula et al evaluated efficacy of UST for treatment of EIM 20 . Notably, the overall rate of EIM resolution was comparable between UST and placebo at week 6 (36.9% vs. 39.1%) and 52 (76.4% vs. 80%); in the sub‐analysis evaluating the efficacy of UST according to the type of EIM, only erythema nodosum was significantly improved at week 52 of treatment.…”