Safety and efficacy of granulocyte/monocyte apheresis in steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics (ART trial): 12-week interim results

International audienceBACKGROUND AND AIMS: Patients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup.METHODS: This single arm, open-label, multicentre trial (ART) was conducted at 18 centres across the UK, France and Germany. Eligible patients were 18-75 years old with moderate-to-severe, steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics. Patients received ≥5 weekly apheresis sessions with Adacolumn. The primary endpoint was clinical remission rate (clinical activity index ≤4) at Week 12.RESULTS: Eighty-six patients were enrolled. At Week 12, 33/84 (39.3%) of patients in the intention-to-treat population achieved clinical remission, with 47/84 (56.0%) achieving a clinical response (clinical activity index reduction of ≥3). Clinical remission was achieved in 30.0% of patients with prior immunosuppressant and biologic failure; steroid-free clinical remission and response were observed in 22.6% and 35.7% of these patients, respectively. Quality of life (Short Health Scale) significantly improved at Week 12 (p\textless0.0001). The majority of adverse events were of mild/moderate intensity.CONCLUSIONS: At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgrou

Once versus three times daily dosing of oral budesonide for active Crohn's disease : A double-blind, double-dummy, randomised trial

Note: J.Pokrotnieks is in the list of the main authors of the article, as well as in the list of International Budenofalk Study Group collaboration list. His surname is made visible as the main author in this bibliographic record. Funding Information: The study was funded by Dr Falk Pharma GmbH, Freiburg, Germany . The study sponsor contributed to the design of the study in collaboration with the authors, funded the analysis of the data by an independent biostatistics company, worked in conjunction with the authors to interpret the data, and reviewed the draft manuscript. The sponsor was not involved in data collection. The final decision to publish was made by the first author (AD).Background: Oral budesonide 9. mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9. mg dose may improve adherence and thereby efficacy. Methods: An eight-week, double-blind, double-dummy randomised trial compared budesonide 9. mg OD versus 3. mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI < 150 at week 8 (last observation carried forward). Results: The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n = 377; 188 [9 mg OD], 189 [3 mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9. mg OD versus 3. mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of - 3.9% (95% CI [- 14.6%; 6.4%]; p = 0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3. mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥ 1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3 mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients. Conclusions: Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3 mg TID dosing in mild-to-moderately active Crohn's disease.publishersversionPeer reviewe

The PROPER Study; A 48-week, pan-European, real-world study of biosimilar SB5 following transition from reference adalimumab in patients with immune-mediated inflammatory disease

Background: The non-interventional PROPER study generated real-world evidence on clinical outcomes following transition in routine practice from reference adalimumab to the EMA-approved SB5 biosimilar adalimumab in patients with immune-mediated inflammatory disease. Methods: Adults with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), Crohn’s disease (CD), or ulcerative colitis (UC) were enrolled at 63 sites across Europe. Eligible patients received ≥ 16 weeks of routine treatment with reference adalimumab before transitioning to SB5, and were followed for 48 weeks post-transition. The primary objective was to evaluate candidate predictors (clinically relevant baseline variables with incidence ≥ 15% by indication cohort) associated with persistence on SB5 at 48 weeks post-initiation. Key primary outcome measures were persistence on SB5 (estimated by Kaplan–Meier methodology) and clinical characteristics and disease activity scores at the time of transition to SB5 treatment (baseline). Results: A total of 955 eligible patients were enrolled (RA, n = 207; axSpA, n = 127; PsA, n = 162; CD, n = 447; UC, n = 12), of whom 932 (97.6%) completed follow-up and 722 (75.6%) were still receiving SB5 at week 48. Kaplan–Meier estimates (95% confidence interval, CI) of persistence on SB5 at week 48 for RA, axSpA, PsA, and CD were 0.86 (0.80–0.90), 0.80 (0.71–0.86), 0.81 (0.74–0.86), and 0.72 (0.67–0.76), respectively. The single candidate predictor associated with probability of SB5 discontinuation before week 48 was female sex [RA, axSpA, and CD cohorts; HR (95% CI): 3.53 (1.07–11.67), 2.38 (1.11–5.14), and 2.21 (1.54–3.18), respectively]. Disease activity scores remained largely unchanged throughout the study, with proportions by cohort in remission at baseline versus week 48 being 59.2% versus 57.2%, 81.0% versus 78.0%, 94.7% versus 93.7%, and 84.0% versus 85.1% for patients with RA, axSpA, PsA, and CD, respectively. Similarly, the SB5 dosing regimen remained unchanged for the majority of patients from baseline to week 48, the most common regimen being 40 mg every 2 weeks. In total, 232 patients (24.3%) reported at least one adverse drug reaction, and most events were mild; eight patients (3.9%) in the RA cohort experienced nine serious adverse events (SAEs; two possibly related to SB5); eight patients (4.9%) in the PsA cohort experienced nine SAEs (one possibly related to SB5); 22 patients (4.9%) in the CD cohort experienced 27 SAEs (four possibly related to SB5); and no SAEs were observed in the UC cohort. Conclusions: With the exception of female sex in RA, axSpA, and CD, none of the candidate predictors were associated with SB5 discontinuation. Persistence on SB5 was high, treatment effectiveness was maintained, and no safety signals were detected. Trial Registration: This trial is registered with ClinicalTrials.gov: NCT04089514

The management of iron deficiency in inflammatory bowel disease

__Background__ Iron deficiency is a common and undertreated problem in inflammatory bowel disease (IBD). __Aim__ To develop an online tool to support treatment choice at the patient-specific level. __Methods__ Using the RAND/UCLA Appropriateness Method (RUAM), a European expert panel assessed the appropriateness of treatment regimens for a variety of clinical scenarios in patients with non-anaemic iron deficiency (NAID) and iron deficiency anaemia (IDA). Treatment options included adjustment of IBD medication only, oral iron supplementation, high-/low-dose intravenous (IV) regimens, IV iron plus erythropoietin-stimulating agent (ESA), and blood transfusion. The panel process consisted of two individual rating rounds and three plenary discussion meetings. __Results__ The panel reached agreement on 71% of treatment indications. 'No treatment' was never considered appropriate, and repeat treatment after previous failure was generally discouraged. For 98% of scenarios, at least one treatment was appropriate. Adjustment of IBD medication was deemed appropriate in all patients with active disease. Use of oral iron was mainly considered an option in NAID and mildly anaemic patients without disease activity. IV regimens were often judged appropriate, with high-dose IV iron being the preferred option in 77% of IDA scenarios. Blood transfusion and IV+ESA were indicated in exceptional cases only. __Conclusions__ The RUAM revealed high agreement amongst experts on the management of iron deficiency in patients with IBD. High-dose IV iron was more often considered appropriate than other options. To facilitate dissemination of the recommendations, panel outcomes were embedded in an online tool, accessible via http://ferroscope.com/

European Crohn's and Colitis Organisation Topical Review on prediction, diagnosis and management of fibrostenosing Crohn's disease

This ECCO topical review of the European Crohn's and Colitis Organisation [ECCO] focused on prediction, diagnosis, and management of fibrostenosing Crohn's disease [CD]. The objective was to achieve evidence-supported, expert consensus that provides guidance for clinical practice

The impact of clinical experience on decision-making regarding the treatment and management of mild-to-moderate ulcerative colitis.

peer reviewe

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

Modelling the benefits of an optimised treatment strategy for 5-ASA in mild-to-moderate ulcerative colitis.

peer reviewedOBJECTIVES: 5-aminosalicylate (mesalazine; 5-ASA) is an established first-line treatment for mild-to-moderate ulcerative colitis (UC). This study aimed to model the benefits of optimising 5-ASA therapy. METHODS: A decision tree model followed 10 000 newly diagnosed patients with mild-to-moderately active UC through induction and 1 year of maintenance treatment. Optimised treatment (maximising dose of 5-ASA and use of combined oral and rectal therapy before treatment escalation) was compared with standard treatment (standard doses of 5-ASA without optimisation). Modelled data were derived from published meta-analyses. The primary outcomes were patient numbers achieving and maintaining remission, with an analysis of treatment costs for each strategy conducted as a secondary outcome (using UK reference costs). RESULTS: During induction, there was a 39% increase in patients achieving remission through the optimised pathway without requiring systemic steroids and/or biologics (6565 vs 4725 for standard). Potential steroidal/biological adverse events avoided included: seven venous thromboembolisms and eight serious infections. Out of the 6565 patients entering maintenance following successful induction on 5-ASA, there was a 21% reduction in relapses when optimised (1830 vs 2311 for standard). This translated into 297 patients avoiding further systemic steroids and 214 biologics. Optimisation led to an average net saving of £272 per patient entering the model for the induction and maintenance of remission over 1 year. CONCLUSION: Modelling suggests that optimising 5-ASA therapy (both the inclusion of rectal 5-ASA into a combined oral and rectal regimen and maximisation of 5-ASA dose) has clinical and cost benefits that supports wider adoption in clinical practice