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
Arkenbosch, J.H.C.; Beelen, E.M.J.; Dijkstra, G.; Romberg-Camps, M.; Duijvestein, M.; Hoentjen, F.; ... ; Dutch Initiative Crohns Colitis IC 2022
Background To prevent recurrence after ileocolonic resection [ICR] in Crohn's disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This... Show moreBackground To prevent recurrence after ileocolonic resection [ICR] in Crohn's disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This study aimed to evaluate postoperative CD recurrence after implementation of a clinical management algorithm and to determine the predictive value of clinical and histological risk factors [RFs]. Methods In this multicentre, prospective cohort study, CD patients [>= 16 years] scheduled for ICR were included. The algorithm advised no postoperative medication for low-risk patients, and treatment with prophylaxis [immunosuppressant/biological] for high-risk patients [>= 1 RF: active smoking, penetrating disease, prior ICR]. Clinical and histological RFs [active inflammation, granulomas, plexitis in resection margins] for endoscopic recurrence [Rutgeerts' score >= i2b at 6 months] were assessed using logistic regression and ROC curves based on predicted probabilities. Results In total, 213 CD patients after ICR were included [age 34.5 years; 65% women] (93 [44%] low-risk; 120 [56%] high-risk: 45 [38%] smoking; 51 [43%] penetrating disease; 51 [43%] prior ICR). Adherence to the algorithm was 82% in low-risk [no prophylaxis] and 51% in high-risk patients [prophylaxis]. Endoscopic recurrence was higher in patients treated without prophylaxis than with prophylaxis in both low [45% vs 16%, p = 0.012] and high-risk patients [49% vs 26%, p = 0.019]. Clinical risk stratification including the prescription of prophylaxis corresponded to an area under the curve [AUC] of 0.70 (95% confidence interval [CI] 0.61-0.79). Clinical RFs combined with histological RFs increased the AUC to 0.73 [95% CI 0.64-0.81]. Conclusion Adherence to this management algorithm is 65%. Prophylactic medication after ICR prevents endoscopic recurrence in low- and high-risk patients. Clinical risk stratification has an acceptable predictive value, but further refinement is needed. Show less
Arkenbosch, J.H.C.; Beelen, E.M.J.; Dijkstra, G.; Romberg-Camps, M.; Duijvestein, M.; Hoentjen, F.; ... ; Dutch Initiative Crohns Colitis IC 2022
BackgroundTo prevent recurrence after ileocolonic resection [ICR] in Crohn’s disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This... Show moreBackgroundTo prevent recurrence after ileocolonic resection [ICR] in Crohn’s disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This study aimed to evaluate postoperative CD recurrence after implementation of a clinical management algorithm and to determine the predictive value of clinical and histological risk factors [RFs].MethodsIn this multicentre, prospective cohort study, CD patients [≥16 years] scheduled for ICR were included. The algorithm advised no postoperative medication for low-risk patients, and treatment with prophylaxis [immunosuppressant/biological] for high-risk patients [≥1 RF: active smoking, penetrating disease, prior ICR]. Clinical and histological RFs [active inflammation, granulomas, plexitis in resection margins] for endoscopic recurrence [Rutgeerts’ score ≥i2b at 6 months] were assessed using logistic regression and ROC curves based on predicted probabilities.ResultsIn total, 213 CD patients after ICR were included [age 34.5 years; 65% women] (93 [44%] low-risk; 120 [56%] high-risk: 45 [38%] smoking; 51 [43%] penetrating disease; 51 [43%] prior ICR). Adherence to the algorithm was 82% in low-risk [no prophylaxis] and 51% in high-risk patients [prophylaxis]. Endoscopic recurrence was higher in patients treated without prophylaxis than with prophylaxis in both low [45% vs 16%, p = 0.012] and high-risk patients [49% vs 26%, p = 0.019]. Clinical risk stratification including the prescription of prophylaxis corresponded to an area under the curve [AUC] of 0.70 (95% confidence interval [CI] 0.61–0.79). Clinical RFs combined with histological RFs increased the AUC to 0.73 [95% CI 0.64–0.81].ConclusionAdherence to this management algorithm is 65%. Prophylactic medication after ICR prevents endoscopic recurrence in low- and high-risk patients. Clinical risk stratification has an acceptable predictive value, but further refinement is needed. Show less
