Ustekinumab for Crohn’s Disease: Results of the ICC Registry, a Nationwide Prospective Observational Cohort Study

Abstract

Background and Aims Ustekinumab is approved for the treatment of Crohn’s disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practice. Methods We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index [HBI]), biochemical (C-reactive protein [CRP] and faecal calprotectin [FCP]), extra-intestinal manifestations and, peri-anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at weeks 0, 12, 24, and 52. The primary outcome was corticosteroid-free clinical remission. Results In total, 221 CD patients were included (98.6% anti-tumour necrosis factor [TNF] and 46.6% vedolizumab exposed) with a median follow-up of 52.0 weeks [interquartile range 49.3–58.4]. Corticosteroid-free clinical remission rates at weeks 24 and 52 were 38.2% and 37.1%, respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate [20.0% vs 42.6%, p = 0.01], but comparable corticosteroid-free clinical remission at week 52 (46.3% [q8w] vs 34.6% [q12w], p = 0.20). There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy [combi 40.6% vs mono 36.0%, p = 0.64]. At baseline, 28 patients had active peri-anal fistula, of whom 35.7% showed complete clinical resolution after 24 weeks. During follow-up we encountered six severe infections [3.5 per 100 patient-years], with all patients being on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 [33.9%] patients mainly due to lack of response. Conclusion Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti-TNF and anti-integrin therapies.

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

“…With 89 treatment‐related adverse events per 100 patient years, the rate of adverse events in tofacitinib‐treated patients was relatively high when compared with other treatments given to anti‐TNF exposed patients . A recent review of clinical trials showed a comparable safety profile of tofacitinib when compared with vedolizumab and anti‐TNF with the exception of herpes zoster infections/reactivations .…”

“…We were able to compare the real‐world total number of tofacitinib‐related adverse events with other treatments prescribed to anti‐TNF refractory patients such as vedolizumab (inflammatory bowel disease [IBD]) and ustekinumab (Crohn's disease [CD]) following an identical methodology from our ICC Registry . This comparison yielded 30 treatment‐related adverse events per 100 patient years for vedolizumab, 24 treatment‐related adverse events per 100 patient years for ustekinumab and 89 treatment‐related adverse events per 100 patient years for tofacitinib, suggesting a less desirable profile in terms of adverse events for the latter. The rate of infections was relative low with no severe infections and 43 mild‐to‐moderate infections per 100 patient years including 4 herpes zoster reactivations.…”

“…The ICC Registry is a prospective, nationwide and observational registry of inflammatory bowel disease (IBD) patients initiating pre‐specified IBD therapies in everyday care in the Netherlands. The design and rationale have previously been described in detail . In short, IBD patients aged 16 years or older are included in eight university and seven non‐university hospitals.…”

A comparative analysis of tioguanine versus low‐dose thiopurines combined with allopurinol in inflammatory bowel disease patients

“…In this multicenter cohort study, LDTA patients of ≥16 years with prior failure to conventional thiopurines due to adverse events and without biological treatment at baseline were identified in the prospective, multicenter Dutch ‘Initiative on Crohn and Colitis’ (ICC) Registry. The ICC Registry was developed to determine the effectiveness, safety and usage of specific IBD treatments in the Netherlands, as previously described 14,15 . In short, IBD patients initiating LDTA were included in four tertiary referral centres and one teaching hospital and were followed for 2 years with a predefined follow‐up schedule of outpatient visits designed to closely follow regular care (week 0, 12, 24, 52, and 104).…”

Vedolizumab for Inflammatory Bowel Disease: Two‐Year Results of the Initiative on Crohn and Colitis (ICC) Registry, A Nationwide Prospective Observational Cohort Study

“…The ICC Registry is a nationwide, observational registry with prospective follow‐up of patients with IBD starting prespecified IBD therapies in the Netherlands. The design and rationale of the ICC Registry were described previously in more detail . Briefly, patients with IBD, ≥ 16 years, in 8 academic and 4 nonacademic hospitals are followed for 2 years after initiating prespecified therapies.…”