The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium

Abstract

INTRODUCTION:We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).METHODS:This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.RESULTS:A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49–0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48–0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients.DISCUSSION:UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Early transmural healing and its predictors assessed by magnetic resonance enterography in patients with Crohn’s disease receiving ustekinumab

“…In the SUCCESS trial, patients with biologic exposure experienced significantly reduced rates of radiographic remission at 12 months compared to biologic-naïve patients. 14 However, there were no differences in prior biologic therapy between the TH and no-TH group in our study ( p = 0.678). Prior usage of biologics was also not associated with likelihood of TH in patients at W26 ( p = 0.404).…”

“… 13 , 30 Another real-world clinical study (SUCCESS trial) showed that 30% of patients with CD achieved radiographic remission at 12 months after UST treatment. 14 In our study, only 18.9% patients achieved TH at W26 of UST therapy. The lower rates of TH in our study were due to the shorter follow-up time and the different definitions.…”

“…The STARDUST trial defined transmural remission as normalization of all IUS parameters; in the SUCCESS trial, radiographic remission was defined as the absence of imaging features of active inflammation based on interpretation by a local radiologist. 13 , 14 We defined TH as BWT ⩽ 3 mm without any signs of inflammation using MRE. Although previous studies have demonstrated an excellent agreement between IUS and MRE in the detection of bowel lesions, it is challenging for different modalities to define TH by a consistent definition.…”

“… 11 , 12 In patients with CD receiving 1-year UST treatment, the cumulative rates of clinical remission (CR) and MH were both nearly 40%. 13 , 14 Serum UST concentrations are associated with outcomes in patients with CD. 15 However, early TH has rarely been assessed using MRE, and risk factors associated with TH in UST therapy remain unclear.…”

Remission of refractory Crohn's disease with anti‐IL‐12/23 therapy in a patient undergoing hemodialysis: A case report

“…Although the efficacy and safety of ustekinumab treatment in CD has been well established, 7 there is still limited data regarding its use in patients with impaired renal function. As an IgG monoclonal antibody, ustekinumab clearance is governed primarily by intracellular catabolism mechanisms and is not depended on glomerular filtration or enzymatic degradation by the liver 8 .…”