INTRODUCTION: The prognostic value of the modified Rutgeerts score (mRS) in patients with Crohn's disease (CD) needs to be further elucidated. This study assessed the prognostic value of the mRS... Show moreINTRODUCTION: The prognostic value of the modified Rutgeerts score (mRS) in patients with Crohn's disease (CD) needs to be further elucidated. This study assessed the prognostic value of the mRS for long-term outcomes after primary ileocecal resection in patients with CD.METHODS: Patients with CD after primary ileocecal resection with an available mRS at first postoperative ileocolonoscopy (index mRS) were retrospectively included. The primary outcome was surgical recurrence. Secondary outcomes were clinical recurrence and progression to severe endoscopic recurrence (≥i3). Cox proportional hazard models were used to assess the association between index mRS and outcomes.RESULTS: Six hundred fifty-two patients were included (mean follow-up: 6.4 years, SD: 4.6). Surgical recurrence rates were 7.7%, 5.3%, 12.9%, 19.1%, 28.8%, 47.8% for index mRS i0, i1, i2a, i2b, i3, and i4, respectively. Clinical recurrence occurred in 42.2% (i0), 53.7% (i1), 58.5% (i2a), 80.2% (i2b), 79.4% (i3), and 95.3% (i4) of patients. Progression to severe endoscopic recurrence occurred in 21.1% (i0), 33.9% (i1), 26.8% (i2a), and 33.3% (i2b) of patients. An index mRS of i2b (adjusted hazard ratio [aHR] 3.0; 1.5–5.6), i3 (aHR 4.0; 2.0–7.9) and i4 (aHR 8.0; 4.0–16.0) were associated with surgical recurrence. An index mRS of i1 (aHR 1.7; 1.2–2.4), i2a (aHR 1.7; 1.2–2.4), i2b (aHR 4.4; 3.2–6.0), i3 (aHR 3.6; 2.5–5.2), and i4 (aHR 7.3; 4.8–10.9) were associated with clinical recurrence. An index mRS of i1 (aHR 2.0; 1.1–3.7) or i2b (aHR 2.5; 1.4–4.6) was associated with progression to severe endoscopic recurrence.DISCUSSION: The increasing mRS corresponds closely with the risk of surgical and clinical recurrence. An index mRS ≥ i2b is associated with surgical recurrence, an index mRS ≥ i1 is associated with clinical recurrence, and i1 or i2b with progression to severe endoscopic recurrence. These results support tight monitoring of disease activity and treatment optimization in patients with ileal lesions and a more conservative management in patients with anastomotic lesions. Show less
Background and AimsWe aimed to assess cost-effectiveness of increasing adalimumab dose intervals compared to the conventional dosing interval in patients with Crohn’s disease [CD] in stable... Show moreBackground and AimsWe aimed to assess cost-effectiveness of increasing adalimumab dose intervals compared to the conventional dosing interval in patients with Crohn’s disease [CD] in stable clinical and biochemical remission.DesignWe conducted a pragmatic, open-label, randomized controlled non-inferiority trial, comparing increased adalimumab intervals with the 2-weekly interval in adult CD patients in clinical remission. Quality of life was measured with the EQ-5D-5L. Costs were measured from a societal perspective. Results are shown as differences and incremental net monetary benefit [iNMB] at relevant willingness to accept [WTA] levels.ResultsWe randomized 174 patients to the intervention [n = 113] and control [n = 61] groups. No difference was found in utility (difference: −0.017, 95% confidence interval [−0.044; 0.004]) and total costs (−€943, [−€2226; €1367]) over the 48-week study period between the two groups. Medication costs per patient were lower (−€2545, [−€2780; −€2192]) in the intervention group, but non-medication healthcare (+€474, [+€149; +€952]) and patient costs (+€365 [+€92; €1058]) were higher. Cost–utility analysis showed that the iNMB was €594 [−€2099; €2050], €69 [−€2908; €1965] and −€455 [−€4,096; €1984] at WTA levels of €20 000, €50 000 and €80 000, respectively. Increasing adalimumab dose intervals was more likely to be cost-effective at WTA levels below €53 960 per quality-adjusted life year. Above €53 960 continuing the conventional dose interval was more likely to be cost-effective.ConclusionWhen the loss of a quality-adjusted life year is valued at less than €53 960, increasing the adalimumab dose interval is a cost-effective strategy in CD patients in stable clinical and biochemical remission. Show less
Background: Despite its effectiveness in treating Crohn's disease, adalimumab is associated with an increased risk of infections and high health-care costs. We aimed to assess clinical outcomes of... Show moreBackground: Despite its effectiveness in treating Crohn's disease, adalimumab is associated with an increased risk of infections and high health-care costs. We aimed to assess clinical outcomes of increased adalimumab dose intervals versus conventional dosing in patients with Crohn's disease in stable remission. Methods: The LADI study was a pragmatic, open-label, multicentre, non-inferiority, parallel, randomised controlled trial, done in six academic hospitals and 14 general hospitals in the Netherlands. Adults (aged >= 18 years) diagnosed with luminal Crohn's disease (with or without concomitant perianal disease) were eligible when in steroid-free clinical and biochemical remission (defined as Harvey-Bradshaw Index [HBI] score <5, faecal calprotectin <150 mu g/g, and C-reactive protein <10 mg/L) for at least 9 months on a stable dose of 40 mg subcutaneous adalimumab every 2 weeks. Patients were randomly assigned (2:1) to the intervention group or control group by the coordinating investigator using a secure web-based system with variable block randomisation (block sizes of 6, 9, and 12). Randomisation was stratified on concomitant use of thiopurines and methotrexate. Patients and health-care providers were not masked to group assignment. Patients allocated to the intervention group increased adalimumab dose intervals to 40 mg every 3 weeks at baseline and further to every 4 weeks if they remained in clinical and biochemical remission at week 24. Patients in the control group continued their 2-weekly dose interval. The primary outcome was the cumulative incidence of persistent flares at week 48 defined as the presence of at least two of the following criteria: HBI score of 5 or more, C-reactive protein 10 mg/L or more, and faecal calprotectin more than 250 mu g/g for more than 8 weeks and a concurrent decrease in the adalimumab dose interval or start of escape medication. The non-inferiority margin was 15% on a risk difference scale. All analyses were done in the intention-to-treat and per-protocol populations. This trial was registered at ClinicalTrials.gov, NCT03172377, and is not recruiting. Findings Between May 3, 2017, and July 6, 2020, 174 patients were randomly assigned to the intervention group (n=113) or the control group (n=61). Four patients from the intervention group and one patient from the control group were excluded from the analysis for not meeting inclusion criteria. 85 (50%) of 169 participants were female and 84 (50%) were male. At week 48, the cumulative incidence of persistent flares in the intervention group (three [3%] of 109) was non-inferior compared with the control group (zero; pooled adjusted risk difference 1 center dot 86% [90% CI -0 center dot 35 to 4 center dot 07). Seven serious adverse events occurred, all in the intervention group, of which two (both patients with intestinal obstruction) were possibly related to the intervention. Per 100 person-years, 168 center dot 35 total adverse events, 59 center dot 99 infection-related adverse events, and 42 center dot 57 gastrointestinal adverse events occurred in the intervention group versus 134 center dot 67, 75 center dot 03, and 5 center dot 77 in the control group, respectively. Interpretation The individual benefit of increasing adalimumab dose intervals versus the risk of disease recurrence is a trade-off that should take patient preferences regarding medication and the risk of a flare into account. Show less
Background: A considerable proportion of Crohn's disease patients that undergo ileocecal resection (ICR) have failed anti-tumor necrosis factor (TNF) therapy preoperatively. This study aimed to... Show moreBackground: A considerable proportion of Crohn's disease patients that undergo ileocecal resection (ICR) have failed anti-tumor necrosis factor (TNF) therapy preoperatively. This study aimed to assess the effectiveness of retreatment of anti-TNF therapy in patients with postoperative recurrence. Methods: A real-world cohort study was performed on Crohn's disease patients who underwent primary ICR after anti-TNF therapy failure, and who were retreated with anti-TNF therapy for postoperative symptomatic Crohn's disease. The primary outcome was treatment failure (the need for (re)introduction of corticosteroids, immunosuppressants, or biologicals or the need for re-resection). Sub-analyses were performed on the nature of preoperative anti-TNF failure (primary non-response, secondary loss of response, intolerance), indication for ICR (refractory, stricturing, penetrating disease), combination therapy with immunomodulators, retreatment with the same anti-TNF agent and preoperative exposure to 1 vs. >1 anti-TNF agents. Results: In total, 66 of 364 patients retreated with anti-TNF therapy following ICR. Cumulative rates of treatment failure at 1 and 2 years were 28% and 47%. Treatment failure rate at 2 years was significantly lower in patients receiving combination therapy as compared to anti-TNF monotherapy (30% vs. 49%, P = 0.02). No difference in treatment failure was found with regards to the nature of preoperative anti-TNF failure (P = 0.76), indication for ICR (P = 0.88) switch of anti-TNF agent (P = 0.55) agent, and preoperative exposure to 1 vs. >1 anti-TNF agents (P = 0.88). Conclusion: Retreatment with anti-TNF therapy for postoperative Crohn's disease recurrence is a valid strategy after preoperative failure. Combination therapy is associated with a lower rate of treatment failure. Show less
Straatmijer, T.; Schaik, F.D.M. van; Bodelier, A.G.L.; Visschedijk, M.; Vries, A.C. de; Ponsioen, C.Y.; ... ; Duijvestein, M. 2022
Background: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months... Show moreBackground: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. Aim: The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. Methods: Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] <= 2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) <= 5 mg/L and faecal calprotectin (FC) <= 250 mu g/g), safety, and discontinuation rate. Results: We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. Conclusion: Tofacitinib was effective in 31.8% of patients after 24 months of treatment. Show less
Straatmijer, T.; Schaik, F.D.M. van; Bodelier, A.G.L.; Visschedijk, M.; Vries, A.C. de; Ponsioen, C.Y.; ... ; Duijvestein, M. 2022
BackgroundTofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of... Show moreBackgroundTofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment.AimThe aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands.MethodsPatients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 μg/g), safety, and discontinuation rate.ResultsWe included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7–34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years.ConclusionTofacitinib was effective in 31.8% of patients after 24 months of treatment. Show less
Straatmijer, T.; Schaik, F.D.M. van; Bodelier, A.G.L.; Visschedijk, M.; Vries, A.C. de; Ponsioen, C.Y.; ... ; Duijvestein, M. 2022
BackgroundTofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of... Show moreBackgroundTofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment.AimThe aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands.MethodsPatients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 μg/g), safety, and discontinuation rate.ResultsWe included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7–34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years.ConclusionTofacitinib was effective in 31.8% of patients after 24 months of treatment. Show less
Huinink, S.T.; Jong, D.C. de; Nieboer, D.; Thomassen, D.; Steyerberg, E.W.; Dijkgraaf, M.G.W.; ... ; Vries, A.C. de 2022
Background Anti-tumor necrosis factor (TNF) therapy is effective for the treatment of Crohn's disease. Cessation may be considered in patients with a low risk of relapse. We aimed to externally... Show moreBackground Anti-tumor necrosis factor (TNF) therapy is effective for the treatment of Crohn's disease. Cessation may be considered in patients with a low risk of relapse. We aimed to externally validate and update our previously developed prediction model to estimate the risk of relapse after cessation of anti-TNF therapy. Methods We performed a retrospective cohort study in 17 Dutch hospitals. Crohn's disease patients in clinical, biochemical or endoscopic remission were included after anti-TNF cessation. Primary outcome was a relapse necessitating treatment. Discrimination and calibration of the previously developed model were assessed. After external validation, the model was updated. The performance of the updated prediction model was assessed in internal-external validation and by using decision curve analysis. Results 486 patients were included with a median follow-up of 1.7 years. Relapse rates were 35 and 54% after 1 and 2 years. At external validation, the discriminative ability of the prediction model was equal to that found at the development of the model [c-statistic 0.58 (95% confidence interval (CI) 0.54-0.62)], though the model was not well-calibrated on our cohort [calibration slope: 0.52 (0.28-0.76)]. After an update, a c-statistic of 0.60 (0.58-0.63) and calibration slope of 0.89 (0.69-1.09) were reported in internal-external validation. Conclusion Our previously developed and updated prediction model for the risk of relapse after cessation of anti-TNF in Crohn's disease shows reasonable performance. The use of the model may support clinical decision-making to optimize patient selection in whom anti-TNF can be withdrawn. Clinical validation is ongoing in a prospective randomized trial. Show less
Arkenbosch, J.H.C.; Mak, J.W.Y.; Ho, J.C.L.; Beelen, E.M.J.; Erler, N.S.; Hoentjen, F.; ... ; Vries, A.C. de 2022
Background: The Crohn's disease (CD) phenotype differs between Asian and Western countries and may affect disease management, including decisions on surgery. This study aimed to compare the... Show moreBackground: The Crohn's disease (CD) phenotype differs between Asian and Western countries and may affect disease management, including decisions on surgery. This study aimed to compare the indications, postoperative management, and long-term prognosis after ileocecal resection (ICR) in Hong Kong (HK) and the Netherlands (NL). Methods: CD patients with primary ICR between 2000 and 2019 were included. The endpoints were endoscopic (Rutgeerts score >= i2b and/or radiologic recurrence), clinical (start or switch of inflammatory bowel disease medication), and surgical recurrences. Cumulative incidences of recurrence were estimated with a Bayesian multivariable proportional hazards model. Results: Eighty HK and 822 NL patients were included. The most common indication for ICR was penetrating disease (HK: 32.5%, NL: 22.5%) in HK vs stricturing disease (HK: 32.5%, NL: 48.8%) in the NL (P < .001). Postoperative prophylaxis was prescribed to 65 (81.3%) HK patients (28 [35.0%] aminosalicylates [5-aminosalicylic acid]; 30 [37.5%] immunomodulators; 0 biologicals) vs 388 (47.1%) NL patients (67 [8.2%] 5-aminosalicylic acid; 187 [22.8%] immunomodulators; 69 [8.4%] biologicals; 50 [6.1%] combination therapy) (P < .001). Endoscopic or radiologic evaluation within 18 months was performed in 36.3% HK vs 64.1% NL (P < .001) patients. No differences between both populations were observed for endoscopic (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.24-1.21), clinical (HR, 0.91; 95% CI, 0.62-1.32), or surgical (HR, 0.61; 95% CI, 0.31-1.13) recurrence risks. Conclusion: The main indication for ICR in CD patients is penetrating disease in HK patients and stricturing disease in NL patients. Although considerable pre- and postoperative management differences were observed between the two geographical areas, the long-term prognosis after ICR is similar.Lay Summary This is the first study reporting similar long-term prognoses after ileocecal resection in Crohn's disease in low- and high-incidence countries despite differences in Crohn's disease phenotype at diagnosis, surgical approach, indications, and pre- and postoperative management including prophylactic medication. Show less
Arkenbosch, J.H.C.; Mak, J.W.Y.; Ho, J.C.L.; Beelen, E.M.J.; Erler, N.S.; Hoentjen, F.; ... ; Vries, A.C. de 2022
BackgroundThe Crohn’s disease (CD) phenotype differs between Asian and Western countries and may affect disease management, including decisions on surgery. This study aimed to compare the... Show moreBackgroundThe Crohn’s disease (CD) phenotype differs between Asian and Western countries and may affect disease management, including decisions on surgery. This study aimed to compare the indications, postoperative management, and long-term prognosis after ileocecal resection (ICR) in Hong Kong (HK) and the Netherlands (NL).MethodsCD patients with primary ICR between 2000 and 2019 were included. The endpoints were endoscopic (Rutgeerts score ≥i2b and/or radiologic recurrence), clinical (start or switch of inflammatory bowel disease medication), and surgical recurrences. Cumulative incidences of recurrence were estimated with a Bayesian multivariable proportional hazards model.ResultsEighty HK and 822 NL patients were included. The most common indication for ICR was penetrating disease (HK: 32.5%, NL: 22.5%) in HK vs stricturing disease (HK: 32.5%, NL: 48.8%) in the NL (P < .001). Postoperative prophylaxis was prescribed to 65 (81.3%) HK patients (28 [35.0%] aminosalicylates [5-aminosalicylic acid]; 30 [37.5%] immunomodulators; 0 biologicals) vs 388 (47.1%) NL patients (67 [8.2%] 5-aminosalicylic acid; 187 [22.8%] immunomodulators; 69 [8.4%] biologicals; 50 [6.1%] combination therapy) (P < .001). Endoscopic or radiologic evaluation within 18 months was performed in 36.3% HK vs 64.1% NL (P < .001) patients. No differences between both populations were observed for endoscopic (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.24-1.21), clinical (HR, 0.91; 95% CI, 0.62-1.32), or surgical (HR, 0.61; 95% CI, 0.31-1.13) recurrence risks.ConclusionThe main indication for ICR in CD patients is penetrating disease in HK patients and stricturing disease in NL patients. Although considerable pre- and postoperative management differences were observed between the two geographical areas, the long-term prognosis after ICR is similar. Show less
Aims: Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin [IL]-12 and IL-23. It is registered for the treatment of inflammatory bowel... Show moreAims: Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin [IL]-12 and IL-23. It is registered for the treatment of inflammatory bowel diseases. We assessed the 2-year effectiveness and safety of ustekinumab in a real world, prospective cohort of patients with Crohn's disease [CD].Methods: Patients who started ustekinumab were prospectively enrolled in the nationwide Initiative on Crohn and Colitis [ICC] Registry. At weeks 0, 12, 24, 52 and 104, clinical remission Harvey Bradshaw Index <= 4 points], biochemical remission (faecal calprotectin <= 200 mu g/g and/or C-reactive protein <= 5 mg/L], perianal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. The primary outcome was corticosteroid-free clinical remission at week 104.Results; In total, 252 CD patients with at least 2 years of follow-up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission was 32.3% [81/251], 41.4% [104/251], 39% [97/249] and 34.0% [84/247] at weeks 12, 24, 52 and 104, respectively. In patients with combined clinical and biochemical disease activity at baseline [n = 122], the corticosteroid-free clinical remission rates were 23.8% [29/122], 35.2% [43/122], 40.0% [48/120] and 32.8% [39/119] at weeks 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks in all patients was 64.3% and 54.8%, respectively. The main reason for discontinuing treatment after 52 weeks was loss of response [66.7%]. No new safety issues were observed.Conclusion: After 104 weeks of ustekinumab treatment, one-third of CD patients were in corticosteroid-free clinical remission. Show less
Asscher, V.E.R.; Biemans, V.B.C.; Pierik, M.J.; Dijkstra, G.; Lowenberg, M.; Marel, S. van der; ... ; Dutch Initiative Crohn Colitis IC 2020
Background Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD). Aims To evaluate the association... Show moreBackground Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD). Aims To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD. Methods IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid-free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders. Results We included 203 vedolizumab- and 207 ustekinumab-treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9-104.0) and 48.4 (IQR 24.4-55.1) weeks, median follow-up time 104.0 (IQR 103.1-104.0) and 52.0 weeks (IQR 49.3-100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022-1.883,P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127-2.231,P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034-2.541,P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes. Conclusions Comorbidity - but not age - is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients. Show less
Biemans, V.B.C.; Woude, C.J. van der; Dijkstra, G.; Meulen-de Jong, A.E. van der; Lowenberg, M.; Boer, N.K. de; ... ; Dutch Initiative Crohn Colitis ICC 2020
Background Both vedolizumab and ustekinumab can be considered for the treatment of Crohn's disease (CD) when anti-TNF treatment fails. However, head-to-head trials are currently not available or... Show moreBackground Both vedolizumab and ustekinumab can be considered for the treatment of Crohn's disease (CD) when anti-TNF treatment fails. However, head-to-head trials are currently not available or planned.Aim To compare vedolizumab and ustekinumab in Crohn ' s disease patients in a prospective registry specifically developed for comparative studies with correction for confounders.Methods Crohn ' s disease patients, who failed anti-TNF treatment and started vedolizumab or ustekinumab in standard care as second-line biological, were identified in the observational prospective Dutch Initiative on Crohn and Colitis Registry. Corticosteroid-free clinical remission (Harvey Bradshaw Index <= 4), biochemical remission (C-reactive protein <= 5 mg/L and fecal calprotectin <= 250 mu g/g), combined corticosteroid-free clinical and biochemical remission, and safety outcomes were compared after 52 weeks of treatment. To adjust for confounding and selection bias, we used multiple logistic regression and propensity score matching.Results In total, 128 vedolizumab- and 85 ustekinumab-treated patients fulfilled the inclusion criteria. After adjusting for confounders, ustekinumab-treated patients were more likely to achieve corticosteroid-free clinical remission (odds ratio [OR]: 2.58, 95% CI: 1.36-4.90, P = 0.004), biochemical remission (OR: 2.34, 95% CI: 1.10-4.96, P = 0.027), and combined corticosteroid-free clinical and biochemical remission (OR: 2.74, 95% CI: 1.23-6.09, P = 0.014), while safety outcomes (infections: OR: 1.26, 95% CI: 0.63-2.54, P = 0.517; adverse events: OR: 1.33, 95% CI: 0.62-2.81, P = 0.464; hospitalisations: OR: 0.67, 95% CI: 0.32-1.39, P = 0.282) were comparable between the two groups. The propensity score matched cohort with sensitivity analyses showed comparable results.Conclusion Ustekinumab was associated with superior effectiveness outcomes when compared to vedolizumab while safety outcomes were comparable after 52 weeks of treatment in CD patients who have failed anti-TNF treatment. Show less
Background Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).Aim To evaluate effectiveness, safety and use of tofacitinib in daily practice.Methods UC... Show moreBackground Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).Aim To evaluate effectiveness, safety and use of tofacitinib in daily practice.Methods UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] <= 2), biochemical remission (faecal calprotectin level <= 250 mu g/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation.Results In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively.Conclusion Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients. Show less
IMPORTANCE For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier... Show moreIMPORTANCE For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function.OBJECTIVE To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes.DESIGN, SETTING, AND PARTICIPANTS The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for <= 2 months or weak opioids for <= 6 months) were included. The 18-month follow-up period ended in March 2018.INTERVENTIONS There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed.MAIN OUTCOMES AND MEASURES The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality.RESULTS Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach.CONCLUSIONS AND RELEVANCE Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings. Show less
Biemans, V.B.C.; Meulen-de Jong, A.E. van der; Woude, C.J. van der; Lowenberg, M.; Dijkstra, G.; Oldenburg, B.; ... ; Dutch Initiative Crohn Colitis ICC 2020
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... Show moreBackground 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. Show less
