Indirect Treatment Comparison of Ustekinumab Versus Other Biologics In Moderate To Severe Crohn’s Disease: A 1-Year Treatment Sequence Analysis

Abstract

Objectives: Graft-versus-host disease (GVHD) is a severe complication of allogenic stem cell transplantation. Preliminary data suggest the potential role of ruxolitinib as a new treatment option in patients with corticosteroid-refractory GVHD. The aim of the present study was to explore the effectiveness and safety of ruxolitinib as a salvage therapy in this population. MethOds: A single-center, retrospective, observational study was carried out. Inclusion criteria: all patients with corticosteroidrefractory GVHD treated with ruxolitinib until June 2016. Collected variables: age, sex, underlying disease, GVHD location, type (acute or chronic) and grade, previous therapies, Eastern Cooperative Oncology Group (ECOG) performance status at baseline, daily dose of ruxolitinib, treatment response and grade ≥ 3 adverse events (AE). Data sources: pharmacy information system and clinical charts review. Results: 13 patients met the inclusion criteria. 46% were male, with a median age of 46 years (range:32-51). The majority of patients (77%) had an ECOG performance status = 1. The most frequent underlying condition was myeloid acute leukemia. Most of the patients (77%) had more than one part of the body affected, being the most affected the cutaneous and gastrointestinal locations. GVHD was chronic in 62% of patients, and 54% had grade ≥ 3 GVHD. The median number of previous GVHD-therapies was 3 (range: 3-5). The most frequency therapies were corticosteroids, inmmunosuppression therapies with tacrolimus and rapamycin, and photopheresis. The median daily dose of ruxolitib was 20 (range: 5-25) mg. The overall response rate was 77% (complete response: 23%, partial response: 54%). Esophageal affectation in one patient was the only AE ≥ 3 recorded. cOnclusiOns: Ruxolitinib appears to be an effective and safe treatment option for patients with GVHD who are refractory to corticosteroids and other available therapies. Randomized control trials are needed to confirm these promising results.

Comparative effectiveness of ustekinumab or vedolizumab after one year in 130 patients with anti‐TNF‐refractory Crohn’s disease

“…Similar to cohort studies, the observation from indirect comparisons of randomised trials is also conflicting. For instance, Pacou et al suggested a higher likelihood for superior efficacy with ustekinumab compared to vedolizumab in anti‐TNF refractory Crohn's disease in an indirect treatment comparison of patients from randomised trials of various biologics though the results failed to achieve statistical significance 16 . Another indirect comparison study noted no significant differences in safety or efficacy between the two agents in treating anti‐TNF refractory Crohn's disease 17 .…”

Cost-effectiveness of ustekinumab in moderate to severe Crohn’s disease in Sweden

“…A treatment sequence analysis was therefore the most plausible option to obtain long-term relative efficacy. Not only did this increase the comparability between maintenance trial placebo arms, it also allowed an evaluation of effect over the full treatment sequence [ 36 ].…”

“…41 publications reporting results from 31 different RCTs met the inclusion criteria. Network meta-analyses (NMAs) of short-term efficacy (probabilities of response or remission) for the induction phase were conducted for each population using a Bayesian framework [ 36 ]. As the identified maintenance trials were deemed not comparable for an NMA, comparative efficacy for the maintenance phase was estimated by means of a treatment sequence analysis, considering both induction and maintenance data.…”

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

“…Ustekinumab is a drug treatment in the latter category, targeting interleukin (IL)-12 and IL-23, that is indicated for the treatment of adult patients with moderately to severely active CD who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNFα antagonist or have medical contraindications to such therapies [ 1 ]. The positioning of UST in particular versus anti-integrin medications is a topic of active discussion in the clinical literature [ 2 , 3 ].…”