Straatmijer, T.; Akker-van Marle, M.E. van den; Ponsioen, C.Y.; Horst, D. van der; Scherpenzeel, M.P.M.; Duijvestein, M.; Meulen-de Jong, A.E. van der 2023
IntroductionSince the number of medical treatment options for Ulcerative Colitis (UC) has expanded over the last decades, patients and physicians face challenges regarding decisions about the... Show moreIntroductionSince the number of medical treatment options for Ulcerative Colitis (UC) has expanded over the last decades, patients and physicians face challenges regarding decisions about the medication options. We aimed to identify patients' preferences about their UC treatment options in the Netherlands. Furthermore, we assessed after how many failed treatment options, patients are willing to consider surgical treatment.MethodsWe conducted a web-based, multicenter, discrete choice experiment (DCE) among adult UC patients. Patients were repeatedly asked to choose between two hypothetical medicinal treatment options. The choice tasks were based on administration route, administration location, chance of symptom reduction (on short and long term) and chances on infection and other adverse events. Data were analyzed by using Hierarchical Bayes estimation.ResultsA total of 172 UC patients participated in the DCE. More than half were anti-TNF experienced (52.9%). The chance of symptom reduction after one year (relative importance (RI) 27.7 (95% CI 26.0-29.4)) was most important in choosing between medicinal treatments, followed by the chance of infection (RI 22.3 (21.4 - 23.3)) and chance of symptom reduction after eight weeks (RI 19.5 (18.3 - 20.6)). Considering surgical treatment, nineteen patients (14.3%) would not even consider surgery after failing eight treatment options without any new available therapies left. Nine patients would consider surgery before trying any treatment options.ConclusionWe found that symptom reduction after one year was the most important attribute in choosing between treatments in UC patients. These outcomes can help understand the trade-offs and preferences of UC patients. Show less
Objective: It is unknown whether ustekinumab (UST) levels can predict clinical outcomes in Crohn's disease (CD) patients. We assessed the exposure-response relationship of UST trough concentrations... Show moreObjective: It is unknown whether ustekinumab (UST) levels can predict clinical outcomes in Crohn's disease (CD) patients. We assessed the exposure-response relationship of UST trough concentrations with biochemical outcomes at week 24 in a prospective, real-world setting. Methods: We performed a prospective study in patients with CD starting UST in four academic centres in the Netherlands. All patients received a weight-adjusted intravenous (IV) UST induction dose, followed by one subcutaneous (SC) dose of 90 mg UST at 8 weeks. Maintenance therapy consisted of 90 mg subcutaneous UST every 8 or 12 weeks. Individual UST concentration time course during treatment were estimated using a population pharmacokinetic (PK) model. Quartile analysis and logistic regression were performed to analyse if UST concentrations at week 8 were associated with biochemical remission rates at week 24 (C-reactive protein (CRP) <= 5 mg/L and / or faecal calprotectin (FC) <= 250 mg/kg). Results: In total, 124 patients with CD were included. Patients achieving biochemical remission at week 12 and 24 had significantly higher UST levels at week 8 compared to patients without biochemical remission (6.6 mu g/mL versus 3.9 mu g/mL, P < 0.01 and 6.3 mu g/mL versus 3.9 mu g/mL, P < 0.01, respectively). In quartile analysis, patients with UST levels in the highest quartile (>= 6.3 mu g/mL at week 8) had higher biochemical remission rates at week 12 and week 24. There was no association between UST levels at and corticosteroid-free clinical remission rates .Conclusion: In this real-world cohort of patients with CD, UST levels in the highest quartile (>= 6.3 mu g/mL) at week 8 were associated with higher biochemical remission rates at week 24. Show less
Volkers, A.; Straatmijer, T.; Duijvestein, M.; Lowenberg, M.; Meulen, A. van der; D'Haens, G. 2023
BACKGROUND & AIMS: Clinicians face difficulty in when and in what order to position biologics and Janus kinase in-hibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory... Show moreBACKGROUND & AIMS: Clinicians face difficulty in when and in what order to position biologics and Janus kinase in-hibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry. METHODS: Patients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index 52), biochemical remission (C-reactive protein 55 mg/L or fecal calprotectin 5250 mg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. RESULTS: Overall, 83 vedolizumab-and 65 tofacitinib-treated patients were included. Propensity score -weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81-10.50; P < .01; OR, 3.02; 95% CI, 1.89-4.84; P < .01; and OR, 1.86; 95% CI, 1.15-2.99; P = .01; and OR, 3.27; 95% CI, 1.96-5.45; P < .01; OR, 1.87; 95% CI, 1.14-3.07; P = .01; and OR, 1.81; 95% CI, 1.06-3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events. CONCLUSIONS: Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes. Show less
Straatmijer, T.; Biemans, V.B.C.; Visschedijk, M.; Hoentjen, F.; Vries, A. de; Bodegraven, A.A. van; ... ; Initiative Crohn Colitis 2022
Background & AimsClinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitorsin patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative...Show moreBackground & AimsClinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitorsin patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry.MethodsPatients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index ≤2), biochemical remission (C-reactive protein ≤5 mg/L or fecal calprotectin ≤250 μg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias.ResultsOverall, 83 vedolizumab- and 65 tofacitinib-treated patients were included. Propensity score-weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81–10.50; P < .01; OR, 3.02; 95% CI, 1.89–4.84; P < .01; and OR, 1.86; 95% CI, 1.15–2.99; P = .01; and OR, 3.27; 95% CI, 1.96–5.45; P < .01; OR, 1.87; 95% CI, 1.14–3.07; P = .01; and OR, 1.81; 95% CI, 1.06–3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events.ConclusionsTofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes. Show less
Straatmijer, T.; Biemans, V.B.C.; Visschedijk, M.; Hoentjen, F.; Vries, A. de; Bodegraven, A.A. van; ... ; Initiative Crohn Colitis 2022
Background & AimsClinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative... Show moreBackground & AimsClinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry.MethodsPatients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index ≤2), biochemical remission (C-reactive protein ≤5 mg/L or fecal calprotectin ≤250 μg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias.ResultsOverall, 83 vedolizumab- and 65 tofacitinib-treated patients were included. Propensity score-weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81–10.50; P < .01; OR, 3.02; 95% CI, 1.89–4.84; P < .01; and OR, 1.86; 95% CI, 1.15–2.99; P = .01; and OR, 3.27; 95% CI, 1.96–5.45; P < .01; OR, 1.87; 95% CI, 1.14–3.07; P = .01; and OR, 1.81; 95% CI, 1.06–3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events.ConclusionsTofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes. 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
Volkers, A.; Straatmijer, T.; Duijvestein, M.; Sales, A.; Levran, A.; Schaik, F. van; ... ; Dutch Initiative Crohn Colitis 2022
Background Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions. Aim To assess the effectiveness, safety and... Show moreBackground Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions. Aim To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD. Methods In this prospective cohort study, patients with IBD who had >= 4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24. Results We included 135 patients, 82 with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) CD and five (9.4%) UC patients discontinued SC vedolizumab after a median of 18 (IQR 8-22) and 6 weeks (IQR 5-10), respectively. Four patients (all CD) switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median vedolizumab serum concentrations increased from 19 mu g/ml at the time of the switch to 31 mu g/ml 12 weeks after the switch (p < 0.005). Conclusions Switching from IV to SC vedolizumab maintenance treatment is effective in patients with CD or UC. However, 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles. 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
