Early Mucosal Healing Predicts Favorable Outcomes in Patients With Moderate to Severe Ulcerative Colitis Treated With Golimumab: Data From the Real-life BE-SMART Cohort.

Background: Golimumab (GOL) is registered for moderate to severely active ulcerative colitis (UC). Data on the use of GOL in daily clinical practice are limited. Currently, it is unclear which factors are predictive of a favorable outcome. The goals of this study were to evaluate the mid-term outcome of GOL (week 26) in patients with moderate to severe UC and to determine predictors of favorable outcome. Methods: Patients included in the SMART study (NCT02155335) were evaluated for their mid-term outcome. Demographic data, disease characteristics, and medical history were recorded retrospectively. Data on disease activity based on total Mayo score, previous and concomitant medication, GOL dosing, mucosal healing (Mayo 0 or 1), adverse events (colectomy, hospitalization), and biomarkers (C-reactive protein, fecal calprotectin, hemoglobin, and albumin) were collected at baseline and weeks 2, 6, 14, 26, and 52. GOL was dosed at 200 and 100 mg at weeks 0 and 2, respectively, and 50 mg (/=80 kg body weight) every 4 weeks thereafter. The primary end point was steroid-free GOL continuation at week 26. Results: From the 91 evaluable patients (42% female; median age, 42 years; median disease duration, 5 years), 4% were active smokers, 25% had extensive colitis, and 38% had an endoscopic Mayo score of 3 at baseline. The median (interquartile range [IQR]) baseline Mayo score was 9 (8-10). Although 75% of patients had previously failed immunomodulators (IMMs), the majority (87%) were anti-tumor necrosis factor (TNF) naive. GOL was started in combination with IMM in 40% and steroids in 64%. The median (IQR) duration of GOL therapy during follow-up was 35.7 (11.4-105.7) weeks. Twenty-six weeks after GOL induction, 37 patients (41%) were steroid-free and still on GOL, of whom 8 (21.6%) required GOL dose optimization. Short-term mucosal healing (STMH) at week 14 was evaluated in 60% of the patients. Considering the whole cohort, only 40% achieved STMH. No predictors could be retained of short-term treatment outcome. In multivariate analysis, STMH was predictive of steroid-free GOL continuation at week 26 (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.90-16.29; P = 0.002) and week 52 (OR, 9.38; 95% CI, 2.68-32.84; P < 0.001). In patients continuing GOL after week 14, STMH was predictive of intervention-free survival (OR, 2.05; 95% CI, 1.09-3.86; P = 0.026) and discontinuation-free survival (OR, 3.47; 95% CI, 1.58-7.58; P = 0.002). During follow-up, 78% needed an intervention, 68% discontinued GOL, and 3 patients needed a colectomy. Conclusions: Real-life data confirm the moderate effectiveness of GOL on the mid-term in active UC, but therapeutic interventions are frequently needed. Short-term mucosal healing predicts a favorable outcome. 10.1093/ibd/izy219_video1izy219.video15798038438001

Early Mucosal Healing Predicts Favorable Outcomes in Patients With Moderate to Severe Ulcerative Colitis Treated With Golimumab: Data From the Real-life BE-SMART Cohort.

Golimumab (GOL) is registered for moderate to severely active ulcerative colitis (UC). Data on the use of GOL in daily clinical practice are limited. Currently, it is unclear which factors are predictive of a favorable outcome. The goals of this study were to evaluate the mid-term outcome of GOL (week 26) in patients with moderate to severe UC and to determine predictors of favorable outcome. Patients included in the SMART study (NCT02155335) were evaluated for their mid-term outcome. Demographic data, disease characteristics, and medical history were recorded retrospectively. Data on disease activity based on total Mayo score, previous and concomitant medication, GOL dosing, mucosal healing (Mayo 0 or 1), adverse events (colectomy, hospitalization), and biomarkers (C-reactive protein, fecal calprotectin, hemoglobin, and albumin) were collected at baseline and weeks 2, 6, 14, 26, and 52. GOL was dosed at 200 and 100 mg at weeks 0 and 2, respectively, and 50 mg (<80 kg body weight) or 100 mg (≥80 kg body weight) every 4 weeks thereafter. The primary end point was steroid-free GOL continuation at week 26. From the 91 evaluable patients (42% female; median age, 42 years; median disease duration, 5 years), 4% were active smokers, 25% had extensive colitis, and 38% had an endoscopic Mayo score of 3 at baseline. The median (interquartile range [IQR]) baseline Mayo score was 9 (8-10). Although 75% of patients had previously failed immunomodulators (IMMs), the majority (87%) were anti-tumor necrosis factor (TNF) naïve. GOL was started in combination with IMM in 40% and steroids in 64%. The median (IQR) duration of GOL therapy during follow-up was 35.7 (11.4-105.7) weeks. Twenty-six weeks after GOL induction, 37 patients (41%) were steroid-free and still on GOL, of whom 8 (21.6%) required GOL dose optimization. Short-term mucosal healing (STMH) at week 14 was evaluated in 60% of the patients. Considering the whole cohort, only 40% achieved STMH. No predictors could be retained of short-term treatment outcome. In multivariate analysis, STMH was predictive of steroid-free GOL continuation at week 26 (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.90-16.29; P = 0.002) and week 52 (OR, 9.38; 95% CI, 2.68-32.84; P < 0.001). In patients continuing GOL after week 14, STMH was predictive of intervention-free survival (OR, 2.05; 95% CI, 1.09-3.86; P = 0.026) and discontinuation-free survival (OR, 3.47; 95% CI, 1.58-7.58; P = 0.002). During follow-up, 78% needed an intervention, 68% discontinued GOL, and 3 patients needed a colectomy. Real-life data confirm the moderate effectiveness of GOL on the mid-term in active UC, but therapeutic interventions are frequently needed. Short-term mucosal healing predicts a favorable outcome. 10.1093/ibd/izy219_video1izy219.video15798038438001

Incidence and predictors of success of adalimumab dose escalation and de-escalation in ulcerative colitis : a real-world Belgian cohort study

Background: Adalimumab (ADM) has been shown efficacious in ulcerative colitis (UC). In randomized controlled trials, dose escalation from 40 mg ADM every other week to 40 mg every week was required in 20%-25% of patients within 1 year. Real-life data suggest higher escalation rates. Attempts for dose de-escalation have not been studied yet. We assessed the need for, outcome of, and predictors of dose escalation and de-escalation in a large retrospective cohort of UC patients treated with ADM. Methods: We included 231 consecutive patients from 10 Belgian centers initiating ADM treatment for active UC before September 1, 2015 (follow-up >= 1 year in each patient). We performed detailed chart review to identify variables associated with short-term clinical benefit (based on physician global assessment and absence of rectal bleeding at week 10), success of dose escalation, and dose de-escalation. Backward Cox regression and Wald Logistic regression were used to identify predictive variables. Results: Short-term clinical benefit was achieved in 101 patients (44%) and was less frequent in infliximab failures [37% vs 50%, Odds ratio 0.57 (95% CI 0.34-0.97), P = 0.038]. After a median of 2.8 (1.7-5.1) months, 164 patients (71%) needed ADM discontinuation (n = 35, 15%) or dose escalation (n = 129, 56%). Dose escalation was successful in 77/129 (60%). Dose de-escalation was attempted in 71% (55/77) after a median of 4.3 (2.9-7.2) months and was successful in 80% (43/54). Conclusions: In this cohort, 56% of patients with UC required ADM dose escalation with a 60% success rate. Of note, most patients could be successfully de-escalated later on

Early Mucosal Healing Predicts Favorable Outcomes in Patients With Moderate to Severe Ulcerative Colitis Treated With Golimumab: Data From the Real-life BE-SMART Cohort

Background: Golimumab (GOL) is registered for moderate to severely active ulcerative colitis (UC). Data on the use of GOL in daily clinical practice are limited. Currently, it is unclear which factors are predictive of a favorable outcome. The goals of this study were to evaluate the mid-term outcome of GOL (week 26) in patients with moderate to severe UC and to determine predictors of favorable outcome. Methods: Patients included in the SMART study (NCT02155335) were evaluated for their mid-term outcome. Demographic data, disease characteristics, and medical history were recorded retrospectively. Data on disease activity based on total Mayo score, previous and concomitant medication, GOL dosing, mucosal healing (Mayo 0 or 1), adverse events (colectomy, hospitalization), and biomarkers (C-reactive protein, fecal calprotectin, hemoglobin, and albumin) were collected at baseline and weeks 2, 6, 14, 26, and 52. GOL was dosed at 200 and 100 mg at weeks 0 and 2, respectively, and 50 mg (<80 kg body weight) or 100 mg (≥80 kg body weight) every 4 weeks thereafter. The primary end point was steroid-free GOL continuation at week 26. Results: From the 91 evaluable patients (42% female; median age, 42 years; median disease duration, 5 years), 4% were active smokers, 25% had extensive colitis, and 38% had an endoscopic Mayo score of 3 at baseline. The median (interquartile range [IQR]) baseline Mayo score was 9 (8-10). Although 75% of patients had previously failed immunomodulators (IMMs), the majority (87%) were anti-tumor necrosis factor (TNF) naïve. GOL was started in combination with IMM in 40% and steroids in 64%. The median (IQR) duration of GOL therapy during follow-up was 35.7 (11.4-105.7) weeks. Twenty-six weeks after GOL induction, 37 patients (41%) were steroid-free and still on GOL, of whom 8 (21.6%) required GOL dose optimization. Short-term mucosal healing (STMH) at week 14 was evaluated in 60% of the patients. Considering the whole cohort, only 40% achieved STMH. No predictors could be retained of short-term treatment outcome. In multivariate analysis, STMH was predictive of steroid-free GOL continuation at week 26 (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.90-16.29; P = 0.002) and week 52 (OR, 9.38; 95% CI, 2.68-32.84; P < 0.001). In patients continuing GOL after week 14, STMH was predictive of intervention-free survival (OR, 2.05; 95% CI, 1.09-3.86; P = 0.026) and discontinuation-free survival (OR, 3.47; 95% CI, 1.58-7.58; P = 0.002). During follow-up, 78% needed an intervention, 68% discontinued GOL, and 3 patients needed a colectomy. Conclusions: Real-life data confirm the moderate effectiveness of GOL on the mid-term in active UC, but therapeutic interventions are frequently needed. Short-term mucosal healing predicts a favorable outcome. 10.1093/ibd/izy219_video1izy219.video15798038438001.status: publishe

Outcome of biological therapies and small molecules in ulcerative proctitis : a Belgian multicenter cohort study

Abstract: BACKGROUND & AIMS: Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). METHODS: This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of >= 2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score 1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. RESULTS: In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P = .001), patients treated with vedolizumab (P = .001), patients with moderate endoscopic disease activity (P = .002), and a body mass index <25 kg/m(2) (P = .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P = .006). No new safety signals were observed. CONCLUSIONS: Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered

Assessment of the one-year Efficacy and Safety of Tofacitinib in biologic-refractory patients with Ulcerative Colitis: a real-world Belgian cohort study

peer reviewedIntroduction: Tofacitinib, an oral Janus kinase inhibitor, has been approved in 2018 for the treatment of moderate to severe ulcerative colitis (UC) in Europe. Efficacy and safety data from long-term real-world studies are scarce. Aim: The aim of the study was to evaluate the real-world long-term efficacy and safety of tofacitinib in a Belgian cohort of patients with refractory UC who were exposed to both anti-TNF and vedolizumab. Methods: We performed an observational, national, retrospective multicenter study including all patients whith active UC who started on tofacitinib between November 2018 and August 2019 in 26 Belgian centers (Ethics Committee approval number P2019/429, date: 10/12/2019; amendment for study extension received on 16/07/2020). Data were prospectively collected and retrospectively analyzed according to intention-to-treat. Clinical response (decrease from baseline in partial adapted Mayo score (stool frequency and rectal bleeding) by ≥ 1 and ≥ 30%), clinical remission (Partial Adapted Mayo score ≤ 1), steroid-free clinical remission, endoscopic response (decrease from baseline in Mayo endoscopic subscore of ≥ 1), endoscopic remission (endoscopic Mayo subscore of 0), drug survival, need for colectomy and adverse events (AEs) were assessed at week 8, 16 and 52. Results: A total of 75 patients were included with a median follow-up of 45 weeks (IQR: 19-51). Patients were predominately men (59%), and median age at baseline was 44 years (IQR: 31-59). Median disease duration was 8 years (IQR: 4-17). Fifty-five percent had left-sided UC and 45% had pancolitis. Overall, 72 (96%), 51 (68%) and 6 (8%) patients were exposed to at least 1, 2 or 3 antiTNFs respectively, and 73 (97%) to vedolizumab. At baseline, 42 (56%) patients were under steroids. Median Partial Adapted Mayo score at baseline was 4 (IQR: 3-5), and median endoscopic Mayo subscore was 2 (IQR: 2-3). Thirty-nine (52%) patients required prolonged induction at 10mg twice daily for 8 additional weeks. Dose optimization was needed in 12 (16%) patients due to disease relapse after induction response, 9 (12%) of which could regain response. After 1 year, 52% and 43% of patients had experienced clinical response and clinical remission respectively, and 39% achieved steroid-free clinical remission. Endoscopic response and remission were observed in 37% and 9% of patients. Faecal calprotectin < 250 µg/g at week 16 (OR: 0.03(95%CI: 0.003-0.4)) was a positive predictor of clinical remission at week 52. Overall, 34 (45%) patients discontinued tofacitinib (22 due to primary non response, 11 due to secondary loss of response and 1 due to AE) during follow-up with a median exposure duration of 17 weeks (IQR: 11-42). Among these patients, 6 underwent colectomy for disease worsening after a median treatment duration of 15 weeks (IQR: 11-19) and a median follow-up of 20 weeks (IQR: 12-25) , while the others switched to another medical therapy. Forty AEs were reported in 25 (33%) patients, with only one (pneumonia) leading to treatment discontinuation. The most common AEs were arthralgia and lower respiratory tract infections followed by herpes zoster, urinary tract and upper respiratory tract infections. Two cases of prostate cancer have been reported. No opportunistic infection, venous thromboembolism, pulmonary embolism or cardiovascular event were reported. A statistically significant increase of 43% in the low-density lipoprotein (LDL) level was observed between baseline and week 52 among patients in clinical remission at week 52 , with no significant changes in total cholesterol and high-density lipoprotein (HDL). Conclusions: Tofacitinib effectively induced long-term clinical and endoscopic response and remission in a refractory cohort of patients with UC in a real-world clinical setting. During this one-year follow-up, tofacitinib was relatively well tolerated with respect to adverse events

Archeologisch booronderzoek Reitdiepwijken 3 te Groningen, gemeente Groningen (GR)

Voor het bureauonderzoek wordt verwezen naar MUG Publicatie 2009-23 (De Roller 2009) dat betrekking heeft op de aangrenzende noordelijke percelen. In de afgelopen twee jaar is de situatie niet zodanig gewijzigd dat er aanvullingen op het bureauonderzoek uit 2009 noodzakelijk zijn. Langs de Friesestraatweg loopt mogelijke een geul met bijbehorende oeverwallen. De oeverwallen zijn aantrekkelijke vestigingsplaatsen voor de mens omdat ze over het algemeen wat droger zijn en hoger liggen dan de omgeving. Uit het booronderzoek blijkt dat binnen het onderzoeksgebied een geul aanwezig is, die vermoedelijk rond de jaartelling zover verland is dat ze geen watervoerende functie meer had. Deels op de geulvulling en op de oeverwallen is een vegetatiehorizont aanwezig dat vermoedelijk uit de 3e eeuw stamt. In twee boringen zijn sporen van fosfaat aangetroffen. Het vegetatiehorizont en de fosfaatsporen zijn aanwijzingen voor menselijke activiteit in het onderzoeksgebied. Mogelijk horen de fosfaatsporen bij de nederzetting net ten oosten van het onderzoeksgebied. Deze nederzetting dateert uit het begin van de jaartelling (Hielkema & De Wit 2007). De terreinomstandigheden (oeverwal en de aanwezigheid van een vegetatiehorizont) binnen het onderzoeksgebied zijn zodanig dat er een goede kans is op menselijke sporen uit de periode ijzertijd-nieuwe tijd. Er wordt daarom aanbevolen vervolgonderzoek uit te voeren in de vorm van een proefsleuvenonderzoek waarbij duidelijk moet worden of er daadwerkelijk bewoningsresten aanwezig zij