T Hallinen’s research while affiliated with ESiOR Oy and other places

Background Real-life long-term evidence on ustekinumab treatment response in patients with Crohn’s disease (CD) is scarce. We performed a retrospective non-interventional nationwide chart review study of dosing and long-term clinical outcomes in Finnish CD patients treated with ustekinumab (FINUSTE2, EUPAS30920). Methods FINUSTE2 involved 17 Finnish centres. Eligible patients were adults with CD, receiving an intravenous first dose of ustekinumab during 2017 or 2018. Disease activity data, such as C-reactive protein (CRP), faecal calprotectin (fCal), and the Simple Endoscopic Score for Crohn’s disease (SES-CD) were collected at baseline, 16 weeks, and one year from treatment initiation. A local gastroenterologist at each centre collected the data from health records in an electronic standardised health questionnaire. Results One hundred and fofty-five patients (48% female) with a mean age of 44 and disease duration of 14 years initiated ustekinumab treatment for CD. Table 1 summarises patient characteristics at baseline. After induction consisting of one intravenous dose and one to two subcutaneous doses at 8 to 16 weeks, 140 patients (93%) continued to maintenance treatment with subcutaneous ustekinumab. Of 93 patients with a follow-up of at least one year, 77 were still on ustekinumab. During ustekinumab treatment, SES-CD (10 at baseline, 3 at 1 year, medians, p = 0.033) and CRP (7 mg/l at baseline, 5 mg/l at 1 year, medians, p < 0.001) and fCal (776 μg/g at baseline, 305 μg/g at 1 year, medians, p < 0.001) decreased significantly in those patients with data available. Figure 1 describes changes in fCal levels over time. Conclusion In this nationwide real-life long-term follow-up study, covering all major centres in Finland, ustekinumab treatment of patients with highly refractory and long-standing CD effectively reduced inflammatory activity, assessed by endoscopy, CRP, and fCal.

Background Real-life long-term evidence on ustekinumab treatment in patients with Crohn’s disease (CD) is limited. We performed a retrospective non-interventional nation-wide chart review study of dosing and long-term clinical outcomes in Finnish CD patients treated with ustekinumab (FINUSTE2, EUPAS30920). Methods FINUSTE2 was carried out in 17 Finnish centres. Eligible patients were adults with CD, receiving an intravenous (IV) first dose of ustekinumab during 2017 or 2018. Data on disease activity, dosage, and concomitant medications were collected at baseline, 16 weeks, and 1 year from treatment initiation. All measurements on ustekinumab trough concentrations (TC) were recorded. Results The study included 155 patients (48% female) with a mean age of 44 and disease duration of 14 years. The disease was stricturing or penetrating in 69% of patients, 59% had prior CD-related surgeries, and 96% had a treatment history of at least one biologic agent. After one IV dose and one to two subcutaneous (SC) doses at 8 to 16 weeks, 140 patients (93%) continued to maintenance treatment with SC ustekinumab, of which nearly three-quarters with a dosage interval of 8 weeks (Figure 1). Of 93 patients with a follow-up of at least 1 year, 77 were still on ustekinumab. During follow-up, 55 patients (39%) had their ustekinumab dose adjusted, mostly (n = 44, 31.4%) as a shortening of the dosage interval. Forty-nine patients had in total 65 ustekinumab TC measurements performed, with a mean of 2.2 µg/ml at 16 weeks (n = 23) and 2.7 µg/ml at 1 year (n = 25). In 67% of cases, the reason for measuring TC was lack of or insufficient response. No anti-drug antibodies appeared at any time point. The proportion of patients on ustekinumab monotherapy increased significantly, from 34% (n = 52) at baseline to 54% (n = 79/146; p < 0.001) at 16 weeks and 64% (n = 49/77; p < 0.01) at 1 year. Correspondingly, corticosteroid use decreased significantly, and a trend towards reduced use of immunomodulators was observed (Figure 2). Conclusion In this nationwide real-life study, treatment with ustekinumab in patients with longstanding and complicated CD was persistent and allowed for significant corticosteroid tapering. A vast majority started the maintenance treatment with an 8-week dosage interval and nearly one-third of all patients required a dose increase, suggesting a highly refractory disease phenotype. The lack of detected antidrug antibodies during follow-up indicates low immunogenicity for ustekinumab.

Background and Aims: A retrospective non-interventional, multi-centre patient chart review study was conducted to investigate the association of faecal calprotectin (FC) 1 year (±2 months) after biological therapy initiation with composite event-free survival (CEFS) consisting of surgical procedures, corticosteroid initiation, treatment failure or dose increase in patients with Crohn’s disease (CD). In addition, the correlations of FC and other tests of disease activity were assessed. Materials and methods: Data on Finnish CD patients initiating a biological therapy between 2010 and 2016, were collected. The association of FC and CEFS was analysed with Kaplan-Meier and Cox proportional hazard modelling. The correlations were tested with Pearson’s test. Results: Biological therapy was initiated in 186 patients, of which 87 (46.8%) had FC results available at 1 year and 80 had follow-up exceeding 14 months. The characteristics of patients with and without FC results were similar. Patients with elevated FC (>250 µg/g) had a significantly increased risk of experiencing composite event (HR 3.4, 95% CI: 1.3–8.9; p = .013) when compared to patients with normal FC (FC ≤ 100). No such risk was observed in patients with intermediately increased FC level (100 µg/g < FC ≤ 250 µg/g) (HR 2.2 (95% CI: 0.8–6.2; p = .120). FC value had significant positive correlation with CRP, HBI and leukocyte values when measured at similar timepoints. Conclusions: Elevated level of FC approximately 1 year after the initiation of biological therapy was associated with an increased risk of either surgical procedures, corticosteroid initiation, treatment failure or dose increase (i.e. composite outcome) in patients with CD.

Background There is limited real-life data on ustekinumab (UST) treatment in patients diagnosed with Crohn’s disease (CD). The present study is a retrospective non-interventional chart review of dosing and short-term clinical outcomes in patients with CD who were treated with UST in Finland (FINUSTE, EUPAS 24728 registration). The aim of the study was to describe the current treatment patterns and the positioning of UST, and to observe changes in clinical outcomes. Methods FINUSTE was performed in 13 Finnish hospitals. Eligible patients were adults with confirmed CD who were induced with intravenous UST (approx. 6 mg/kg) during year 2017. UST treatment patterns were explored in dosing frequency, mean and median dose at the induction and maintenance phase. The clinical outcomes were observed as proportion of patients achieving clinical response or remission at 16 weeks and at the end of follow-up. Remission was defined as Harvey–Bradshaw index (HBI) 4 points or less, response as HBI reduction of at least 3 points and clinical benefit as the proportion of patients in remission and/or response. For endoscopic response, the Simple Endoscopic Score for Crohn’s disease (SES-CD) was used. Results 48 patients (54% female) initiated UST treatment for CD. The median age of the patients was 39 years with a median disease duration of 13 years. Fifty-two per cent of the patients had a stricturing, 29% inflammatory and 19% penetrating disease. More than 60% of the patients had CD-related surgeries prior to UST treatment. Out of 48 patients, only 2 (4%) were bionaїve, 25% were treated with one biologic agent and 71% with 2 or 3 biologic agents prior to UST. The average UST induction dose was 5.6 mg/kg and maintenance treatment was initiated in 88% of the induced patients. After initiation of UST, the proportion of patients on corticosteroids decreased from 48% to 25% in 16 weeks. At the end of follow-up, 11% of the patients with follow-up exceeding 16 weeks (n = 37) remained on corticosteroids. Clinical outcomes at 16 weeks and end of follow-up are described in Figure 1. Endoscopic response with ≥50% reduction from baseline in the SES-CD was observed in 67% of patients with endoscopic data (n = 9) at 16 weeks. Conclusions In patients with highly refractory and long-standing CD, the treatment with UST was shown to be effective in inducing short-term clinical benefit and endoscopic response, as well as allowing for significant corticosteroid tapering. View largeDownload slide Figure 1. Clinical outcomes at Week 16 and end of follow-up (on average 8 months of follow-up). View largeDownload slide Figure 1. Clinical outcomes at Week 16 and end of follow-up (on average 8 months of follow-up).

Background Fecal calprotectin (fCal) has been shown to correlate well with endoscopic healing in Crohn’s disease (CD) patients, while less evidence is available on the association of fCal and long-term outcomes such as the need for surgeries. This study was established to analyse whether the surgery free survival (SFS) is associated with the attained fCal-levels 12 months after biological therapy initiation. In addition, the association of fCal-levels at 12 months and composite event free survival (CEFS) was assessed. The composite event was defined as surgical procedure, corticosteroid initiation, treatment failure, or dose increase occurring after the 12-month fCal-measurement. Methods A non-interventional, retrospective patient chart review study was carried out in 4 major Finnish gastroenterology clinics (EUPAS17190 registration). The study included adults (age≥18 years) with confirmed CD diagnosis, who had initiated a biologic therapy for CD at any time between January 1st 2010 and June 30th 2016 (n = 186). Results At the start of follow-up, the patients were on average 44 years old and 49% of them were female. Most of the patients had ileocolonic, non-stricturing/non-penetrating CD. At baseline the mean fCal was 958 mg/g (n = 62) and at 12-months it was 558 mg/g. The mean follow-up time was 1119 days (range 562–1774). CRP, thrombocytes and albumin levels had strong and significant associations with fCal when measured at similar timepoints. The SFS analysis included 4 failures (i.e. surgical procedures) with the mean of 741 days at risk per patient. fCal (mg/g) at 12 months and ileocolonic CD were significant predictors for SFS. The CEFS analysis included 22 failures with the mean of 572 days at risk per patient. fCal (mg/g) at 12 months was the only significant and robust predictor for CEFS in univariate (HR 1.0005, 95% CI 1.0002 – 1.0008, p = 0.003) and multivariate models. Conclusions Among the CD patients, fCal was a robust predictor of composite outcome measured as surgical procedure, corticosteroid initiation, treatment failure or dose increase. fCal was also associated with surgery-free survival.