Mark Andrew Ainsworth

Background: Infliximab (IFX) is used for steroid-refractory acute severe ulcerative colitis (ASUC). We assessed whether baseline IFX clearance (CL) prior to rescue therapy was associated with the use of intensified induction and treatment outcomes. Methods: Retrospective cohort study including patients with ASUC treated with IFX at two tertiary Danish inflammatory bowel disease centres. Baseline IFX CL (L/day) was estimated using a pharmacokinetic model incorporating gender, albumin and antidrug antibodies. Results: Baseline IFX CL was significantly higher by 30% in patients with ASUC (n=74) versus outpatients (n=90) (median 0.456 vs 0.350, pROC ) 0.69 (0.56–0.81), 0.003; sensitivity 0.89 (0.69–0.92), specificity 0.45 (0.13–0.62)). CL was the only variable consistently associated with intensification in univariable and multivariable analyses whereas albumin showed only modest discriminatory performance. Among non-intensified patients with ASUC, those with high baseline IFX CL above the threshold (≥0.42) had numerically higher 1-year colectomy rates than those with low CL (5/27 (19%) vs 1/21 (5%); p=0.20). Conversely, colectomy rates were similar with intensification irrespective of high or low CL (35% vs 33%, p=1.00). Treatment outcomes were comparable regardless of CL in patients avoiding colectomy. Conclusion: Baseline IFX CL was associated with the use of intensified induction in ASUC. High baseline IFX CL prior to therapy initiation may identify patients at risk of insufficient response to standard induction strategies. Prospective validation of CL-guided dosing is warranted.

Background/Objectives: The combined goal of achieving both clinical and endoscopic remission has highlighted the need for strategies that support a treat-to-target approach in inflammatory bowel disease (IBD). A proactive monitoring strategy involves scheduled assessments regardless of symptoms to detect subclinical disease activity and enable timely treatment adjustments, whereas a reactive approach initiates evaluation only in response to clinical deterioration or objective signs of active disease. This study investigated whether proactive monitoring improves the achievement of treatment goals compared with a reactive strategy. Methods: In this prospective cohort study carried out between September 2020 and July 2022, patients with IBD receiving biologic therapy were managed according to a predefined proactive monitoring schedule and prospectively followed for one year. A control group, matched for age, sex, diagnosis, and treatment, was enrolled from another tertiary IBD center using a reactive monitoring strategy; their clinical course over one year was reconstructed retrospectively from medical records. All patients underwent colonoscopy assessment at one year. The primary outcome was treatment failure, defined as inadequate mucosal healing or symptom control, the need for intestinal surgery, or discontinuation of biologic therapy due to insufficient efficacy. Results: A total of 162 patients were included (91 managed proactively and 71 managed reactively). In the intention-to-treat population, treatment failure occurred in 67 patients (74%, 95% confidence interval (CI) 63–84%) in the intervention group and 60 patients (85%, 95% CI 75% to 94%) in the control group (difference 11%, CI −3% to 25%, p = 0.13). In the per-protocol analysis, 44 of 69 patients (64%, CI 50% to 78%) in the intervention group experienced treatment failure compared with 43 of 53 patients (81%, CI 60% to 93%) in the control group (difference 17%, CI −1% to 36%, p = 0.06). Patients in the proactive monitoring group underwent significantly more disease-monitoring assessments than those managed reactively. Conclusions: Proactive monitoring numerically improved combined clinical and endoscopic outcomes compared with reactive management, but this did not reach statistical significance and resulted in substantially greater healthcare resource utilization.

Biological treatment has revolutionised the management of Crohn's disease (CD), however, at baseline (pre-treatment), it is not possible to predict which biologic a patient will respond the best to. This systematic review aimed to identify pre-treatment predictors of response/non-response to infliximab, adalimumab, vedolizumab and ustekinumab and to critically evaluate the available literature. We searched Embase, MEDLINE and Cochrane Registry of Controlled Trials (published from 2014 to 2024) for studies reporting on pre-treatment predictors of response/non-response to infliximab, adalimumab, vedolizumab, ustekinumab in adult (≥18 years) biologically naïve CD patients. Two reviewers independently completed title/abstract screening, full-text reading, data extraction, and quality assessment. The quality of the included studies was evaluated using 'Prediction model Risk Of Bias ASsessment Tool' (PROBAST). A total of 39 studies were eligible for final inclusion. Vedolizumab and ustekinumab were investigated in one study each. For infliximab and adalimumab, we found several potential predictors such as age, body mass index (BMI), disease duration and behaviour, C-reactive protein (CRP), interleukins (ILs) and different imaging characteristics, that could be integrated into future prediction model studies. All studies were judged high risk of bias (RoB) - mainly due to problems regarding analyses and outcome definitions and determinations. No pre-treatment predictors fulfilled the criteria of being an appropriate predictor of response/non-response. This was due to high RoB, conflicting results and a large heterogeneity between the studies. Future studies must be well-designed and follow strict protocols to produce robust results.

Introduction: Biologic therapies, such as vedolizumab (VDZ) and ustekinumab (UST), offer effective treatment options for inflammatory bowel disease. In spite of limited evidence, it is common practice to escalate the dosing regimen if clinical symptoms or biomarkers give suspicion of loss of response. This study aims to determine whether model-informed precision dosing (MIPD) can provide equal efficacy and possibly superior cost-effectiveness compared with symptom-based management. Methods and analysis: This study is an unblinded, randomised controlled trial, conducted at six centres in Denmark. A total of 166 patients diagnosed with Crohn’s disease or ulcerative colitis who have been on stable VDZ or UST therapy for at least 3 months will be enrolled. Participants will be randomised to receive either continued symptom and biomarker-based dosing (control group) or dosing guided by therapeutic drug monitor using pharmacokinetic (PK) models together with PK-pharmacodynamic targets (=MIPD; intervention group). The primary endpoint is the fraction of patients in steroid-free remission at the end of the observation period. Secondary endpoints include mucosal healing, clinical remission, biochemical disease control, PK assessment and cost-effectiveness. Ethics and dissemination: The trial has been approved by the Danish Medicines Agency and The Medical Research Ethics Committee. No study-related procedures will take place before patients have signed written informed consent. Results will be published in peer-reviewed journals and presented at international conferences. Trial registration numbers: EUCT, 2024-517123-39-00; NCT06788340 .

Biologic therapies such as infliximab and adalimumab have transformed the management of inflammatory bowel disease. However, many patients experience primary or secondary loss of response, often due to the development of anti-drug antibodies. The cause of anti-drug antibody formation is thought to be influenced by genetic variations, with human leukocyte antigen alleles—particularly HLA-DQA1*05—emerging as consistent risk factors for immunogenicity, but other candidate variants may also be of importance. To explore the role of genetic predictors in anti-drug antibody development, we systematically reviewed the literature. A search of Medline, Embase, and the Cochrane Library identified 1944 records, of which 27 studies met inclusion criteria. Across these studies, HLA-DQA1*05 carriage was repeatedly associated with higher antibody formation, lower drug levels, treatment failure, and secondary loss of response. Other HLA alleles and FCGR3A variants were also linked to increased risk, while some haplotypes appeared protective. Findings varied depending on the drug, genetic background, and patient population. The role of concomitant immunomodulator therapy was inconsistent, though some genotypes appeared to benefit. Overall, HLA-DQA1*05 and FCGR3A variants are the most reliable predictors of immunogenicity, particularly in infliximab-treated patients. Future work should prioritize large, multi-ethnic prospective studies with standardized antibody measurements and integrated pharmacogenomic approaches to establish clinical utility.

Background: The prevalence of inflammatory bowel disease (IBD) is increasing. While several studies have shown that incorporating a clinical pharmacist into patient care can improve quality of life, evidence specifically addressing their role in IBD management remains limited. Objectives: This study aimed to systematically review the evidence on treatment adherence in IBD, with a focus on the potential role of clinical pharmacist counselling to improve medication adherence. Methods: Three databases (PubMed, MEDLINE and Embase) were searched to identify relevant literature, using keywords derived from the PICO model. Results: Seven full‐text articles met the inclusion criteria. Three of these reported that pharmacist involvement had a positive effect on treatment adherence in patients with IBD. Furthermore, two studies reported that pharmacist involvement in treatment improved disease activity. Patients' perceptions of pharmacist involvement were generally positive, particularly after receiving information about pharmacist services and education. Finally, studies also indicate that pharmacists require greater knowledge of IBD to provide optimal care. Conclusion: Although the available literature is limited, it indicates that involving clinical pharmacists in IBD treatment may have a positive impact—improving medication adherence and enhancing disease control.

The prevalence of patients being diagnosed with inflammatory bowel disease is increasing. While several studies have shown that, in general, it is possible to improve patients’ quality of life with the incorporation of a clinical pharmacist, data on the potential benefits of clinical pharmacist in the treatment of inflammatory bowel disease is more limited. The aim of the present study was to provide a systematic review of benefits of adherence to treatment of inflammatory bowel disease with focus on the potential role of clinical pharmacist counseling. Three databases (PubMed, Medline, and Embase) were used to identify relevant literature. Keywords generated from the PICO model were used for the search. Seven full text articles were identified. They all indicated that pharmacist involvement in treatment could improve quality of life in patients with IBD. Results showed that patient perception of pharmacist involvement was positive following information about pharmacist services and education. Furthermore, results suggest that pharmacist demand better knowledge of inflammatory bowel disease in order to provide better service for IBD patients. The available literature is scarce but indicates that clinical pharmacist involvement in treatment of IBD had positive outcome, and helped improving the patients’ quality of life and their adherence to medication.