Cost-Effectiveness Analysis of Increased Adalimumab Dose Intervals in Crohn's Disease Patients in Stable Remission: The Randomized Controlled LADI Trial.

BACKGROUND AND AIMS: We aimed to assess cost-effectiveness of increasing adalimumab dose intervals compared to the conventional dosing interval in patients with Crohn's disease [CD] in stable clinical and biochemical remission. DESIGN: We conducted a pragmatic, open-label, randomized controlled non-inferiority trial, comparing increased adalimumab intervals with the 2-weekly interval in adult CD patients in clinical remission. Quality of life was measured with the EQ-5D-5L. Costs were measured from a societal perspective. Results are shown as differences and incremental net monetary benefit [iNMB] at relevant willingness to accept [WTA] levels. RESULTS: We randomized 174 patients to the intervention [n = 113] and control [n = 61] groups. No difference was found in utility (difference: -0.017, 95% confidence interval [-0.044; 0.004]) and total costs (-€943, [-€2226; €1367]) over the 48-week study period between the two groups. Medication costs per patient were lower (-€2545, [-€2780; -€2192]) in the intervention group, but non-medication healthcare (+€474, [+€149; +€952]) and patient costs (+€365 [+€92; €1058]) were higher. Cost-utility analysis showed that the iNMB was €594 [-€2099; €2050], €69 [-€2908; €1965] and -€455 [-€4,096; €1984] at WTA levels of €20 000, €50 000 and €80 000, respectively. Increasing adalimumab dose intervals was more likely to be cost-effective at WTA levels below €53 960 per quality-adjusted life year. Above €53 960 continuing the conventional dose interval was more likely to be cost-effective. CONCLUSION: When the loss of a quality-adjusted life year is valued at less than €53 960, increasing the adalimumab dose interval is a cost-effective strategy in CD patients in stable clinical and biochemical remission. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT03172377.

Development and Validation of a Remote Monitoring Tool for Assessment of Mild, Moderate, and Severe Infections in Inflammatory Bowel Disease.

BACKGROUND: Immunomodulators and biologics are cornerstones in the management of inflammatory bowel disease [IBD], but are associated with increased risk of infections. Post-marketing surveillance registries are pivotal to assess this risk, yet mainly focus on severe infections. Data on the prevalence of mild and moderate infections are scarce. We developed and validated a remote monitoring tool for real-world assessment of infections in IBD patients. METHODS: A 7-item Patient-Reported Infections Questionnaire [PRIQ] covering 15 infection categories was developed with a 3-month recall period. Infection severity was defined as mild [self-limiting or topical treatment], moderate [oral antibiotics, antivirals, or antifungals], or severe [hospitalisation or intravenous treatment]. Comprehensiveness and comprehensibility were ascertained through cognitive interviewing of 36 IBD outpatients. After implementation in the telemedicine platform myIBDcoach, a prospective, multicentre cohort study was performed between June 2020 and June 2021 in 584 patients, to assess diagnostic accuracy. Events were cross-checked with general practitioner and pharmacy data [gold standard]. Agreement was evaluated using linear-weighted kappa with cluster-bootstrapping to account for within-patient level correlation. RESULTS: Patient understanding was good and interviews did not result in reduction of PRIQ items. During validation, 584 IBD patients {57.8% female, mean age 48.6 (standard deviaton [SD]: 14.8), disease duration 12.6 years [SD: 10.9]} completed 1386 periodic assessments, reporting 1626 events. Linear-weighted kappa for agreement between PRIQ and gold standard was 0.92 (95% confidence interval [CI] 0.89-0.94). Sensitivity and specificity for infection [yes/no] were 93.9% [95% CI 91.8-96.0] and 98.5% [95% CI 97.5-99.4], respectively. CONCLUSIONS: The PRIQ is a valid and accurate remote monitoring tool to assess infections in IBD patients, providing means to personalise medicine based on adequate benefit-risk assessments.

Faecal gas analysis by electronic nose as novel, non-invasive method for assessment of active and quiescent paediatric inflammatory bowel disease: Proof of principle study.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) and its two phenotypes ulcerative colitis (UC) and Crohn's disease (CD) are essentially assessed by endoscopy, both in initial diagnostic work-up and during follow-up. This carries a high burden, especially on paediatric patients. Faecal volatile organic compounds (VOCs) are considered potential non-invasive biomarkers for intestinal diseases linked to gut microbiota alterations. We hypothesized that faecal VOC analysis by electronic nose allows discrimination of children with CD, UC and controls during active disease and remission. METHODS: Faecal VOC patterns of children with newly diagnosed IBD and controls were studied by an electronic nose (Cyranose 320®), at baseline and upon achieving remission at 6-weeks of follow-up. Disease activity was assessed by global physician's assessment, substantiated by serum C-reactive protein and faecal calprotectin. Internally cross-validated receiver-operator-characteristic curves and corresponding sensitivity and specificity for detection of IBD were calculated RESULTS: Faecal VOC profiles of patients with UC (26) and CD (29) differed from controls (28); in active disease (AUC±95% CI, p-value, sensitivity, specificity: 1.00±0.00; p<0.001, 100%, 100%) and (0.85±0.05, p<0.001, 86%, 67%) and in clinical remission (0.94±0.06, p<0.001, 94%, 94%) and (0.94±0.06, p<0.001, 94%, 94%), respectively. Furthermore, CD-patients differed from UC-patients during active disease (0.96±0.03; p<0.001, 97%, 92%), and upon achieving clinical remission (0.81±0.08, p=0.002, 88%, 72%). CONCLUSION: Faecal VOC analysis allowed discrimination of paediatric patients with IBD from controls, both during active disease and remission. It therefore has potential as non-invasive test, in both diagnostic work-up and assessment of disease activity in IBD.

Association of FcgR2a, but not FcgR3a, with inflammatory bowel diseases across three Caucasian populations.

BACKGROUND: The Fc receptors II and III (FcgR2a, and FcgR3a) play a crucial role in the regulation of the immune response. The FcgR2a*519GG and FcgR3a*559CC genotypes have been associated with several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, nephritis, and possibly to type I diabetes, and celiac disease. In a large multicenter, two-stage study of 6570 people, we tested whether the FcgR2a and FcgR3a genes were also involved in inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We genotyped the FcgR2a*A519G and FcgR3a*A559C functional variants in 4205 IBD patients in six well-phenotyped Caucasian IBD cohorts and 2365 ethnically matched controls recruited from the Netherlands, Spain, and New Zealand. RESULTS: In the initial Dutch study we found a significant association of FcgR2a genotypes with IBD (P-genotype = 0.02); while the FcgR2a*519GG was more common in controls (23%) than in IBD patients (18%; odds ratio [OR] = 0.75; 95% confidence interval [CI] 0.61-0.92; P = 0.004). This association was corroborated by a combined analysis across all the study populations (Mantel-Haenszel [MH] OR = 0.84; 0.74-0.95; P = 0.005) in the next stage. The Fcgr2a*GG genotype was associated with both UC (MH-OR = 0.84; 0.72-0.97; P = 0.01) and CD (MH-OR = 0.84; 0.73-0.97; P = 0.01), suggesting that this genotype confers a protective effect against IBD. There was no association of FcgR3a*A559C genotypes with IBD, CD, or UC in any of the three studied populations. CONCLUSIONS: The FcgR2a*519G functional variant was associated with IBD and reduced susceptibility to UC and to CD in Caucasians. There was no association between FcgR3a*5A559C and IBD, CD or UC.