Secundaire preventie na een residentiële ontwenningsbehandeling voor jongeren

Verslaving is een complexe ziekte met een chronisch verloop en opeenvolgende crisissituaties die een acute aanpak vereisen. Het residentieel programma is een eerste stap in de behandeling. Hier wordt de basis gelegd voor een nieuw, clean leven. In de laatste fase van het residentieel programma ligt de nadruk op resocialisatie: de uitbouw van een nieuwe vriendenkring, zinvolle daginvulling, werk, hobby’s en huisvesting. Eens deze basis er is, wordt de patiënt ‘losgelaten’ en moet hij het waarmaken in het ‘echte’ leven. Hij moet de veiligheid en geborgenheid van de kliniek missen en hij is de eerste maanden na zijn ontslag uiterst kwetsbaar. Het is dan ook belangrijk dat de patiënt in die kwetsbare periode intensief kan opgevolgd worden. Tot nog toe werd de patiënt verwezen naar een ambulante setting met ongekende therapeuten, met wie hij geen binding heeft. De patiënt ziet dit meestal niet zitten en haakt vroegtijdig af, met vaak een herval als gevolg. Om deze ‘missing link’ tussen residentiële behandeling en een stabiel leven op te vullen, werd ons intensief nazorgprogramma ontwikkeld. Het nazorgproject legt de nadruk op een actieve participatie van hulpverlener, patiënt en zijn omgeving en een intensieve wisselwerking tussen de verschillende actoren. Er is een continuïteit van hulpverlening die de zaken verder kan opvolgen en direct kan interveniëren bij crisissituaties. Op deze manier kan vaak een herval vermeden worden of de schade beperkt gehouden

Health-Related Quality of Life Outcomes With Tofacitinib Treatment in Patients With Ulcerative Colitis in the Open-Label Extension Study, OCTAVE Open

BACKGROUND Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We report health-related quality of life (HRQoL) outcomes in patients with ulcerative colitis in the phase 3 open-label, long-term extension study, OCTAVE Open. METHODS The Inflammatory Bowel Disease Questionnaire (IBDQ), EuroQoL-5 Dimensions Health Questionnaire, and 36-Item Short Form Survey scores were analyzed up to month (M) 72 in 4 subpopulations: patients in remission at baseline (maintenance remitters) assigned tofacitinib 5 mg twice daily and patients not in remission at baseline (maintenance nonremitters, maintenance treatment failures, and induction nonresponders [IndNRs]) assigned tofacitinib 10 mg twice daily in OCTAVE Open. Data were analyzed overall and stratified by corticosteroid use at baseline, prior tumor necrosis factor inhibitor failure, and prior immunosuppressant failure. RESULTS Among maintenance remitters and nonremitters, HRQoL outcomes were maintained up to M72: 80.0% and 100.0% of patients had an IBDQ total score ≥170, respectively. At baseline, 7.4% of maintenance treatment failures had an IBDQ total score ≥170, and this increased to 54.3% and 75.0% at M2 and M72, respectively. Corresponding values for IndNRs were 22.6%, 51.0%, and 86.0%. HRQoL outcomes were independent of treatment history. Among patients not in remission at baseline, improvement in EuroQoL-5 Dimensions Health Questionnaire and 36-Item Short Form Survey scores was maintained or achieved by M2, and steady to M72 or M33, with maintenance treatment failures and IndNR subpopulations undergoing the biggest improvements from baseline. CONCLUSIONS A continued favorable impact on HRQoL was revealed with long-term tofacitinib treatment in OCTAVE Open, regardless of baseline remission status or treatment history. (ClinicalTrials.gov; number: NCT01470612)

Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis

Background Tofacitinib is the first in class, pan-JAK inhibitor approved for ulcerative colitis (UC). Clinical efficacy has been shown, but long-term real-life endoscopic and histologic data are lacking. Aim To investigate the effects of tofacitinib in patients with refractory UC focussing on endoscopic, histologic and molecular outcomes, including STAT3 phosphorylation (pSTAT3) detection in the spatial context of mucosal inflammation METHODS: We prospectively monitored 59 highly refractory patients (96.7% anti-TNF exposure, 91.7% vedolizumab exposure) initiating tofacitinib at two IBD referral centres and assessed outcome at the end of induction and after 48 weeks of therapy. Endoscopic improvement was defined as a Mayo endoscopic subscore ≤1, endoscopic and histologic remission as Mayo endoscopic subscore 0 and Nancy histologic score 0. Multiplex immunohistochemistry with multispectral imaging was used to assess pSTAT3. Results Endoscopic improvement was achieved by 24.4% and 30.5% of patients at weeks 8 and 48, respectively. Endoscopic and histologic remission rates were 11.1%, 23.7 and 16.7%, 21.4%, respectively. Endoscopic improvement at week 8 was significantly associated with treatment continuation in the long-term (72.7% vs 20.6%, p = 0.003). Although we observed a gradual decrease of mucosal pSTAT3 levels in both remitters and non-remitters (p < 0.05), no association with treatment outcome could be demonstrated. However, lamina propria pSTAT3 was significantly associated with the Nancy Histologic index (p = 0.004). Conclusion Tofacitinib can induce and maintain endoscopic and histologic remission in up to one-quarter of highly refractory UC patients. Longitudinal monitoring of nuclear pSTAT3 in mucosal tissue compartments reflects distinctive on-target effects, independently of long-term treatment outcomes

Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease

Background: Mucosal IL-13 Receptor alpha 2 (IL13RA2) mRNA expression is one of the best predictive markers for primary non-responsiveness to infliximab therapy in patients with inflammatory bowel disease (IBD). The objective of this study was to understand how IL-13Rα2, a negative regulator of IL-13 signaling, can contribute to IBD pathology.Methods:IL13RA2 knockout (KO) and wild type (WT) mice were exposed to dextran sodium sulfate (DSS) in drinking water to induce colitis. Furthermore, mucosal biopsies and resection specimen of healthy individuals and IBD patients before the start of anti-tumor necrosis factor (anti-TNF) therapy were obtained for immunohistochemistry and gene expression analysis.Results: After induction of DSS colitis, IL13RA2 KO mice had similar disease severity, but recovered more rapidly than WT animals. Goblet cell numbers and mucosal architecture were also more rapidly restored in IL13RA2 KO mice. In mucosal biopsies of active IBD patients, immunohistochemistry revealed that IL-13Rα2 protein was highly expressed in epithelial cells, while expression was restricted to goblet cells in healthy controls. Mucosal IL13RA2 mRNA negatively correlated with mRNA of several goblet cell-specific and barrier genes, and with goblet cell numbers.Conclusions: The data suggest that IL-13Rα2 on epithelial cells contributes to IBD pathology by negatively influencing goblet cell recovery, goblet cell function and epithelial restoration after injury. Therefore, blocking IL-13Rα2 could be a promising target for restoration of the epithelial barrier in IBD

Rapid and Sustained Symptom Relief in Patients With Ulcerative Colitis Treated With Filgotinib: Data From the Phase 2b/3 SELECTION Trial

INTRODUCTION Patients with ulcerative colitis (UC) regard rapid onset of action among the most important aspects of their treatment. We used the partial Mayo Clinic Score (pMCS) and component patient-reported subscores to assess the rapidity and sustainability of response to filgotinib, a once-daily, oral Janus kinase 1 preferential inhibitor, in adults with moderately to severely active UC in the phase 2b/3 SELECTION trial. The association between early symptomatic improvements and health-related quality of life (HRQoL) outcomes was also assessed. METHODS In these post hoc analyses of the double-blinded, randomized, placebo-controlled 58-week SELECTION trial (NCT02914522), rectal bleeding and stool frequency diary data on days 1-15 and pMCS remission and response at multiple time points including weeks 10 and 58 were evaluated. HRQoL was assessed using the Inflammatory Bowel Disease Questionnaire at weeks 10 and 58. RESULTS Filgotinib 200 mg relative to placebo improved rectal bleeding and stool frequency within 7 days ( P &lt; 0.05). By week 2, greater proportions of filgotinib 200 mg-treated patients than placebo-treated patients achieved pMCS remission (biologic-naive, 15.1% vs 8.0%, P = 0.0410; biologic-experienced, 10.3% vs 4.2%, P = 0.0274). A similar treatment effect was observed at week 58 ( P &lt; 0.0001). Day 7 rectal bleeding and stool frequency subscores were associated with the Mayo Clinic Score response at weeks 10 and 58. Patients in pMCS remission at weeks 10 and 58 had greater improvements in the Inflammatory Bowel Disease Questionnaire score than those not in pMCS remission. DISCUSSION Filgotinib 200 mg daily resulted in rapid and sustained improvements in both UC symptoms and HRQoL

Developing a Standard Set of Patient-Centred Outcomes for Inflammatory Bowel Disease—an International, Cross-disciplinary Consensus

Success in delivering value-based healthcare involves measuring outcomes that matter most to patients. Our aim was to develop a minimum Standard Set of patient-centred outcome measures for inflammatory bowel disease (IBD), for use in different healthcare settings.An international working group (n=25) representing patients, patient associations, gastroenterologists, surgeons, specialist nurses, IBD registries and patient-reported outcome measure (PROM) methodologists participated in a series of teleconferences incorporating a modified Delphi process. Systematic review of existing literature, registry data, patient focus groups and open review periods were used to reach consensus on a minimum set of standard outcome measures and risk adjustment variables. Similar methodology has been used in 21 other disease areas (www.ichom.org).A minimum Standard Set of outcomes was developed for patients (aged ≥16) with IBD. Outcome domains included survival and disease control (survival, disease activity/remission, colorectal cancer, anaemia), disutility of care (treatment-related complications), healthcare utilisation (IBD-related admissions, emergency room visits) and patient-reported outcomes (including quality of life, nutritional status and impact of fistulae) measured at baseline and at 6 or 12 month intervals. A single PROM (IBD-Control questionnaire) was recommended in the Standard Set and minimum risk adjustment data collected at baseline and annually were included: demographics, basic clinical information and treatment factors.A Standard Set of outcome measures for IBD has been developed based on evidence, patient input and specialist consensus. It provides an international template for meaningful, comparable and easy-to-interpret measures as a step towards achieving value-based healthcare in IBD

ECCO Position statement on the use of biosimilars for inflammatory bowel disease – An update

status: publishe