Retrospective study.

The purpose of this study was to determine whether IBD in patients with degenerative lumbar changes undergoing primary 1-2LF is associated with higher rates of (1) in-hospital length of stay, (2) medical complications, (3) readmissions, and (4) costs of care.

In the United States, the prevalence of inflammatory bowel disease (IBD) has increased concurrently with an aging population with degenerative disk changes. In these patients, primary 1- to 2-lumbar fusion (1-2LF) is a common procedure to resolve serious complications of the spine. Studies comparing these patient demographics to hospital lengths of stay, postoperative complications, readmission rates, and costs of care are limited in the literature.

The inclusion criteria consisted of patients with IBD who underwent 1-2LF, using a 90-day surveillance period, postoperatively. This 90-day surveillance period was used to measure the length of hospital stay, rates of medical complications, rates of readmissions, and overall costs of care. The IBD cohort was matched against a case-matched cohort group.

Patients in the study group had significantly longer in-hospital lengths of stay. In addition, patients in the study group had significantly higher incidence and odds of developing postoperative medical complications within 90 days. Also, study group patients had significantly higher readmission rates. Finally, patients in the study group had significantly higher costs of care than their case-matched cohort.

This study demonstrated that patients with IBD and degenerative lumbar disease are burdened with longer in-hospital lengths of stay, rates of postoperative medical complications, rates of readmission, and costs of care after undergoing primary 1-2LF.

No research has assessed the comprehensive annual costs of managing ulcerative colitis (UC) patients undergoing biological treatment. This study aimed to determine the annual costs and primary cost drivers for UC patients receiving biological therapy.

This prospective observational study was conducted in Iran from a societal perspective, employing the cost-of-illness method, grounded in human capital theory. A prevalence-based approach and bottom-up technique were used for cost estimation. Inpatient costs were extracted from hospital records, while outpatient service usage and direct non-medical costs over a one-year follow-up were collected through patient interviews. Indirect costs were evaluated using a standardized questionnaire. The average costs per patient were calculated, and the factors affecting patient expenses were analyzed using the Mann-Whitney and Kruskal-Wallis statistical tests.

The study included 238 UC patients (50.8% male; mean age: 37.66 ± 12.13 years), with 32.8% receiving Infliximab (IFX) and 67.2% on Adalimumab (ADA), and an average disease duration of 9.29 ± 6.5 years. The total annual economic burden per UC patient was USD 2316.90. Of this, direct medical costs constituted 49.84%, direct non-medical costs 21.13%, and indirect costs 29.03%. Notably, higher expenses were significantly associated with patients under 20 years of age and those treated with ADA.

Biological therapies accounted for the largest share of direct medical expenses, while productivity losses, mainly resulting from temporary absenteeism, were identified as a major factor contributing to the economic burden of UC in Iran.

Advanced therapies (ADT) that encompass biological agents and small molecules have been approved for the treatment of inflammatory bowel disease (IBD), broadening the spectrum of available treatment options. Nevertheless, a substantial proportion of patients fail to achieve satisfactory responses, necessitating surgical intervention. Treatment objectives have evolved beyond clinical remission, reduction of inflammation, and mucosal healing, shifting focus toward enhancing the quality of life, acknowledging the profound impact of IBD on physical and mental well-being.

This comprehensive review describes the current landscape of ADT for IBD, including dual biologic therapy (DBT), which involves the combination of two biologics or a single biologic with a small-molecule compound, as well as considerations surrounding the discontinuation of biologics.

ADT is the standard treatment for moderate to severe IBD, while DBT appears promising for specific subsets of patients, including those with refractory disease or extraintestinal manifestations. However, these approaches may increase the risk of adverse effects, including malignancy. To optimize individualized treatment strategies in patients with refractory IBD, further trials are needed to refine ADT's predictive value, establish DBT's safety and indications, define biologic discontinuation criteria, and evaluate emerging biomarkers, artificial intelligence, and bowel ultrasound in patient management.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, impose an escalating burden on healthcare systems globally, with a rising prevalence contributing to increased costs. This study explored healthcare utilisation patterns and its drivers amongst IBD patients in an outpatient clinic.

A longitudinal cohort study was conducted at a Dutch academic teaching hospital. IBD patients ( n  = 180) were followed for 1 year and were categorised based on disease activity and consultation frequency. Healthcare utilisation was assessed through consultations and laboratory tests. Patient-reported outcomes and biochemical disease activity were measured, and subsequently the reasons for consultations were analysed.

The frequency of outpatient healthcare utilisation exceeded the recommended IBD care guidelines by two-fold. Comorbidities were the leading reason for consultations (40.4%), followed by remission induction, medication changes and pending test results. Moreover, clinical disease activity, reported problems with self-care, daily activities and pain were predictive of an increase in annual consultations.

This study identified factors influencing healthcare utilisation in IBD outpatients. Personalised care pathways using eHealth technologies have the potential to reduce unnecessary consultations and optimise resource allocation.

Inflammatory bowel diseases (IBDs), primarily encompassing ulcerative colitis and Crohn's disease, represent a challenging spectrum of disorders with a multifaceted pathogenesis. Despite the array of available treatments, a demand for novel therapeutic options persists to achieve remission in a broader patient population. Research findings indicate that relying solely on a single biologic drug may limit future treatment choices, prompting consideration for a more suitable shift from step-up to top-down strategies in certain cases. In the backdrop of advancing drug development, reimagining the application of existing therapies presents a promising avenue. Among these innovative approaches is combination therapy. This review explores the outcomes of recent randomized clinical trials, systematic reviews, and case studies, focusing on dual biologic therapy. It underscores the effectiveness, safety, and tolerability of combining two biologic drugs in IBD, providing insights into a potentially impactful treatment strategy.

Vedolizumab is a gut-selective anti-lymphocyte trafficking biologic indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) in Canada.

The objective of this study was to evaluate the cost effectiveness of treatment sequencing for UC and CD from a public healthcare payer perspective, leveraging new real-world evidence from the literature and the EVOLVE study, a retrospective chart review.

Using separate decision tree/Markov models to assess cost effectiveness for UC and CD, two sequencing approaches were estimated for adult patients (≥ 18 years) diagnosed with UC or CD who were biologic-naïve: vedolizumab as first-line biologic followed by anti-tumor necrosis factor (TNF)-α versus first-line anti-TNFα followed by vedolizumab. Treatment effectiveness (response and remission), surgery rates, dose escalation and regain of response and safety inputs were estimated from EVOLVE, a retrospective chart review of real-world data, and evidence synthesis from the literature, whereas costs and utilities were estimated from health technology assessment reports, clinical trials, and the literature. Biosimilar costs were used for anti-TNFα. Both models simulated a 5-year time horizon and discounted costs and outcomes at 1.5%. Probabilistic base-case analyses (n = 10,000) reported total costs (2023 Canadian dollars) and quality-adjusted life-years (QALYs). Several scenario analyses were conducted to explore robustness of results.

In UC, vedolizumab as a first-line biologic followed by anti-TNFα resulted in an incremental gain of 0.09 QALYs (2.46 vs. 2.55) and saved $7179 ($134,028 vs. $126,848), making this a dominant strategy compared with first-line anti-TNFα followed by vedolizumab. In CD, use of vedolizumab as a first-line biologic resulted in an incremental gain of 0.04 QALYs (3.35 vs. 3.39) at an incremental cost of $50,631 ($89,850 vs. $140,381) versus first-line anti-TNFα followed by vedolizumab (incremental cost-effectiveness ratio of $1,265,775 per QALY).

Based on this analysis, sequencing vedolizumab as a first-line biologic prior to anti-TNFα in UC and CD provided additional clinical benefit to patients. In UC, vedolizumab as a first-line biologic also saved healthcare system costs compared with anti-TNFα, whereas in CD, vedolizumab provided incremental benefit at an incremental cost, which was not considered cost effective at a threshold of $50,000/QALY.

Therapeutic drug monitoring (TDM) for biologic therapies in inflammatory bowel disease (IBD) primarily aims to optimize dosing. However, several unmet needs remain. These include the identification of optimal drug concentrations, accounting for variability in pharmacokinetics (PK) and pharmacodynamics (PD), and the frequent delays between sampling and clinical decision-making. Recent technical advances, such as population PK/PD modeling and model-informed precision dosing (MIPD) tools developed from such models, as well as point-of-care (POC) and self-sampling assays and novel software programs, offer potential solutions. Successful implementation of these innovations may help to establish MIPD for patients with IBD. This would enable personalized dosing, advancing a one-size-fits-all approach to TDM that currently is inadequate to fulfill the needs for every patient with IBD.

Biologic therapies are commonly used for inflammatory bowel disease (IBD) patients. Multiple biologic medicines can now be given both intravenously and subcutaneously. The different administration routes present provide different advantages regarding dose escalation, healthcare resource utilisation, pharmacokinetics, convenience and safety. Comparator effectiveness studies between intravenous and subcutaneous administration are lacking.

Our primary outcome was to compare the effectiveness between intravenous and subcutaneous biologics in rates of clinical remission.

We performed a systematic review and meta-analysis to include all relevant articles from MEDLINE ( Ovid ), EMBASE , PubMed and Cochrane Central Register of Controlled Trials from 1 January 2003 to 28 January 2024. Studies that compared intravenous and subcutaneous administration of the same biologic therapy in IBD patients and reported effectiveness outcomes were included. This study was registered on PROSPERO (CRD42023442675).

Twenty studies met the inclusion criteria for the systematic review. Nine vedolizumab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.99; 95% confidence interval: 0.88, 1.11). Six infliximab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.91; 95% confidence interval: 0.77, 1.08).

Our findings in the first meta-analysis comparing the effectiveness of intravenous and subcutaneous biologic therapies in IBD suggest there is no difference in the effectiveness between these two administration routes. However, further high-quality studies, particularly head-to-head studies are needed to confirm this finding.

Over the last decade, the treatment options for inflammatory bowel disease (IBD) have significantly progressed with the emergence of new medications designed to target various immune pathways and mitigate inflammation. Adalimumab (ADA) is a tumor necrosis factor alpha antagonist and stands as an effective treatment for IBD. In April 2021, the province of British Columbia implemented a mandatory non-medical switch policy of the ADA originator Humira® to ADA biosimilars. Biosimilars offer a potential cost-effective, safe, and efficacious alternative to the originator, yet there remains limited real-world evidence on long-term outcomes of ADA non-medical switching in IBD.

To assess the long-term outcomes of non-medical switching from the ADA originator Humira® to an ADA biosimilar among IBD patients.

A retrospective observational chart review study was conducted on IBD patients eligible for the provincially mandated non-medical switch to an ADA biosimilar. The primary outcome was treatment persistence at 30 months post-switch. Secondary outcomes included the proportion of and reasons for therapy alteration or ADA discontinuation, loss of response (LOR) rates, adverse events (AE), and clinical and biochemical remission status. Patients who remained on the originator throughout the switch period, through compassionate support or private pay, constituted the comparison group.

Patients in the originator (n = 43) and biosimilar switch (n = 228) groups displayed similar demographics and baseline disease characteristics. By the study endpoint of 30 months, there was no difference in the rate of treatment persistence in either group (n = 36, 83.7% originator group vs n = 201, 88.2% biosimilar group, P = 0.451). Treatment persistence demonstrated similar rates of discontinuation between both study groups (log-rank P = 0.543). There was a numerical but not statistically significant difference in rates of adverse outcomes between either group (39.5% originator vs 28.9% biosimilars, P = 0.206). This included comparable rates of LOR (27.9% vs 17.5%) or AE (11.6% vs 11.4%) between the originator and biosimilar cohorts, respectively. C-reactive protein and fecal calprotectin levels were similar one year pre- and post-switch.

These data support the long-term efficacy and safety of non-medical ADA switching in IBD and will help inform patients and physicians in jurisdictions currently undergoing biosimilar switching.

Background: Sex-related treatment disparities are well-documented across various medical conditions, yet their impact on the management of inflammatory bowel disease (IBD) remains underexplored. This study aims to investigate sex-based differences in the management of ulcerative colitis (UC), focusing on both medical and surgical approaches and examining whether biological sex correlates with variations in healthcare utilization. Methods: A systematic search was conducted across multiple databases, including MEDLINE (via PubMed), Google Scholar, the Cochrane Library, and ScienceDirect, to identify studies on sex differences in ulcerative colitis (UC) management up to April 2024. Statistical analysis was performed using RevMan 5.4, with a random-effects model to combine odds ratios (OR) for both primary and secondary outcomes. The study is registered with PROSPERO (CRD42024537750). Results: The meta-analysis included eight observational studies involving 47,089 patients (51.9% females). There were no statistically significant sex differences in biologic therapy use (OR 0.89, 95% CI: 0.69 to 1.15, p = 0.36) or corticosteroid use (OR 1.17, 95% CI: 0.89 to 1.54, p = 0.27). However, females were less likely to use immunomodulators compared to males (OR 0.89, 95% CI: 0.85 to 0.94, p < 0.0001). There were no significant differences in surgical interventions, including total abdominal colectomy. Females had higher annual UC-related hospitalizations compared to males (OR 1.41, 95% CI: 1.22 to 1.64, p < 0.00001). Conclusions: In conclusion, while biologic and surgical treatments showed no significant sex differences, disparities were noted in immunomodulator use and hospitalization rates, underscoring the need for sex-specific UC management strategies.

To identify patient-reported complaints affecting quality of life in Crohn's disease patients with a perianal fistula, and to compare differences between subgroups.

A questionnaire was distributed to 1667 patients from the Dutch Crohn's and Colitis Patients' organization, those patients with Crohn's disease and perianal fistula were included. Patients were asked to report (using free text) their most important fistula-related complaints affecting their quality of life. All responses were structurally analyzed and categorized. Data comparisons were made between subgroups: women versus men, patients with versus without current presence of a seton, and patients aged ≤40 versus >40 years.

Of 743 respondents (44.6%), 123 patients with Crohn's disease and perianal fistula were included (92 women, median age 41 years [IQR 34-56] and 36 with seton). A total of 776 complaints were allocated to 36 categories, with 19 reported in >10% of patients. Perianal fistula-related complaints affected nearly all patients (95.9%). Impact on psychological status (71.7% vs. 29.0%; p < 0.0001) and on sexual activities (37.0% vs. 16.1%; p = 0.003) were more common in women than men. Younger patients more often reported insecurity (38.7% vs. 18.0%; p = 0.026), shame (29.0% vs. 11.5%; p = 0.024), and impact on sexual activities (40.3% vs. 23.0%; p = 0.048) than older patients. Patients with a seton more frequently reported self-experienced malodour (50.0% vs. 23.0%; p = 0.005), physical activity limitations (41.7% vs. 19.5%; p = 0.014), and work/study impact (22.2% vs. 5.7%; p = 0.019).

We identified 19 perianal fistula-related complaints reported by >10% of patients. These complaints may guide improvement of current outcome measures.

Data regarding multiple switches including reverse switching between infliximab and its biosimilars are scarce in the field of inflammatory bowel diseases (IBD).

We investigated the clinical effectiveness as primary outcome measure after repeated switches. Secondary endpoints included C-reactive protein (CRP) levels, immunogenicity (trough levels (TL); anti-drug antibodies (ADA), safety and drug persistence.

This study is a prospective, single-centre, observational cohort study. IBD patients receiving originator infliximab were switched to biosimilar SB2 and then reverse switched after 96 weeks and followed up for another 48 weeks.

Clinical disease activity (Harvey-Bradshaw-index (HBI) in Crohn's disease (CD), partial Mayo score (pMS) in ulcerative colitis (UC)), CRP, TL, ADA, therapy-discontinuations and (serious) adverse events ((S)AE)) were monitored throughout the study.

Ninety-five patients (60 CD, 38 female) were enrolled. The median HBI was 2 (interquartile range (IQR) 1-4) at baseline and 2 (1-4) at week 48, resulting in a mean intra-individual change of 0.0 (standard deviation (SD) 1.5). The median pMS was 1 (IQR 0-1) at baseline and 0.5 (0-1) at week 48 resulting in a mean intra-individual change of 0.0 (SD 0.8). Clinical remission was achieved in 80% at baseline and 82% at week 48. Median CRP 2.0 mg/l (IQR 1.0-4.1) at baseline and 2.4 mg/l (1.1-5.2) at week 48 resulted in a mean change of 1.7 (SD 5.8) and no significant differences in CD (p = 0.3) and UC (p = 0.9). Median TL were 7.2 µg/ml (IQR 3.8-19.3) at baseline and 5.5 µg/ml (3.5-13.1) at week 48, resulting in a mean change of -1.0 (SD 7.4) with no statistical significance (CD p = 0.26, UC p = 0.41). De-novo-ADA were developed by 3.4%. The discontinuation rate was 14.7%. Safety signals were consistent with previous studies.

Reverse switching had no impact on efficacy of infliximab therapy in our cohort of IBD patients. The switch didn't influence immunogenicity or safety of therapy.

During the last two decades, an increased number of molecules with multiple mechanisms of action have been approved for the treatment of inflammatory bowel disease (IBD), with a substantial increase in the costs related to therapy, which has become a concern for payers, regulators, and healthcare professionals. Biosimilars are biologic medical products that are highly structurally similar to their reference products; have no clinically meaningful differences in terms of immunogenicity, safety, or effectiveness; and are available at a lower price. Materials and Methods: This was an observational prospective study conducted in two IBD centres in Bucharest and included 53 patients, 27 male (M) and 26 female (F), diagnosed with IBD according to standard clinical, endoscopic, radiological, and histological criteria, who were non-medically switched at the indication of the National Insurance House to a biosimilar of Adalimumab. Aims: The aim was to determine the rates of clinical remission, adverse effects, and treatment persistence at one year. Results: No significant differences were found in terms of the faecal calprotectin (FC) and C-reactive protein (CRP) levels 6 and 12 months after changing from the originator biologic treatment to a biosimilar. Only one patient required a change in their biological treatment following the clinical and biological loss of response. The main adverse effect reported by the patients was pain at the injection site. Of the 53 patients, only 2 reported pain at the injection site, and 1 patient reported experiencing abdominal pain and rectal bleeding immediately after the switch, but no recurrence was observed clinically or endoscopically. Conclusions: This observational study is the first to be carried out in Romania that shows that, after a non-medical switch, biosimilars of Adalimumab are as efficient and safe as the originator Adalimumab in the clinical treatment of patients with IBD.

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis (UC) that can lead to significant morbidity and mortality, with a substantial number of patients needing colectomy. Infliximab (IFX) has been increasingly used as a rescue therapy for patients who have failed intravenous steroids and has been more frequently used as an induction and maintenance therapy in moderate-to-severe UC. Therefore, the number of patients admitted with ASUC previously exposed to IFX has been increasing, raising additional challenges in the medical management of these patients to avoid emergent colectomy. This narrative review intends to summarise the most recent evidence in the medical management of steroid-refractory ASUC patients previously exposed to IFX and to propose a treatment algorithm for approaching this difficult-to-treat group of patients.

The impact of inflammatory bowel disease [IBD] on work productivity remains unclear. In this systematic review and meta-analysis, we quantify work-related outcomes and employment data among persons with IBD.

A systematic literature search was conducted in MEDLINE, EMBASE, the Cochrane library, Scopus, ProQuest, and clinicaltrials.gov from inception to February 2023, to identify studies on work productivity in persons with IBD aged > 18 years. Work productivity was defined primarily by the Work Productivity and Activity Impairment [WPAI] questionnaire which includes absenteeism, presenteeism, overall work impairment, and non-work activity impairment. In addition, we included data on employment, sick leaves, disability pensions, and indirect costs due to productivity loss. Pooled effect analysis was conducted using a random-effects model for pooled estimates of continuous and proportional data with 95% confidence intervals.

Among all patients with IBD, the pooled estimates were 16.4% for absenteeism, 35.9% for presenteeism, 39.4% for overall work impairment, and 46.0% for non-work activity impairment. Indirect costs from overall work impairment were 5131.09 euros/patient/year. Only two-thirds of IBD patients were employed, and one in three lost their jobs due to IBD. Among those employed, 39.5% report sick days, 21.3% report work disability, and 12.3% receive disability pensions. Most studies demonstrate clinically meaningful improvements in work productivity with medical and/or surgical therapies.

Persons with IBD experience significant work impairment and associated indirect costs. This highlights the need for appropriate workplace accommodations and timely medical therapy to alleviate the burden of disease and improve work outcomes.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurring periods of inflammation and remission, primarily affecting the colon. The concept of medication-related burden, which refers to the adverse effects experienced by patients due to conventional medical treatments, is relatively new in the field. This study aimed to measure medication-related burden among patients with ulcerative colitis in Iraq. The study was conducted at the Gastroenterology and Hepatology Teaching Hospital, Medical City, Baghdad, Iraq, from December 2022 to May 2023. We used the Arabic version of the Living with Medicines Questionnaire version 3 (LMQ-3) to explore medication-related burdens experienced by patients with UC. Eighty-six patients with ulcerative colitis were included. The mean of the total medication-related burden score was 107.5 ± 20.7. The findings showed that 45.3% of patients with UC had a moderate degree of medication-related burden, followed by minimum burden (44.2%), high burden (5.8%), and no burden (4.7%). The lowest median burden scores emerged in five domains: interactions with healthcare professionals, practical difficulties with medication use, medication side effects, medication effectiveness, and the impact on daily life. Conversely, the highest-burden scores were noted in the cost, concerns about medication use, and autonomy to vary the regimen domains. In multivariate analysis, none of the patient-related variables was independently correlated with the total medication-related burden score. A large proportion of the patients with UC who participated in the current study reported varying degrees of medication-related burden, with the majority having a minimum to moderate medication-related burden.

The introduction of anti-tumor necrosis factor α (TNFα) biologics significantly innovated inflammatory bowel disease (IBD) treatment and increased medical costs. The recent expiration of patents of some anti-TNFα biologics (such as infliximab and adalimumab) facilitated the development of biosimilars. Comparable pharmacokinetic, efficacy, safety, and immunogenicity profiles between anti-TNFα originators and biosimilars were demonstrated in different studies. Anti-TNFα biosimilars hold promise for reducing the high cost of biologics and increasing patient access to biologics. In this review, we outline the current data on the use of anti-TNFα originators and biosimilars in patients with IBD, with a focus on the efficacy, safety, and immunogenicity profiles of infliximab and adalimumab biosimilars. The potential benefits, challenges, and future directions of anti-TNFα biosimilars are also discussed in the review.

Data on cost-effectiveness of first-line infliximab in paediatric patients with Crohn's disease are limited. Since biologics are increasingly prescribed and accompanied by high costs, this knowledge gap needs to be addressed.

To investigate the cost-effectiveness of first-line infliximab compared to conventional treatment in children with moderate-to-severe Crohn's disease.

We included patients from the Top-down Infliximab Study in Kids with Crohn's disease randomised controlled trial. Children with newly diagnosed moderate-to-severe Crohn's disease were treated with azathioprine maintenance and either five induction infliximab (biosimilar) infusions or conventional induction treatment (exclusive enteral nutrition or corticosteroids). Direct healthcare consumption and costs were obtained per patient until week 104. This included data on outpatient hospital visits, hospital admissions, drug costs, endoscopies and surgeries. The primary health outcome was the odds ratio of being in clinical remission (weighted paediatric Crohn's disease activity index<12.5) during 104 weeks.

We included 89 patients (44 in the first-line infliximab group and 45 in the conventional treatment group). Mean direct healthcare costs per patient were €36,784 for first-line infliximab treatment and €36,874 for conventional treatment over 2 years (p = 0.981). The odds ratio of first-line infliximab versus conventional treatment to be in clinical remission over 104 weeks was 1.56 (95%CI 1.03-2.35, p = 0.036).

First-line infliximab treatment resulted in higher odds of being in clinical remission without being more expensive, making it the dominant strategy over conventional treatment in the first 2 years after diagnosis in children with moderate-to-severe Crohn's disease.

NCT02517684.

Autoimmune diseases (ADs) represent a heterogeneous group of conditions affecting 5-10% of the global population. In recent decades, hematopoietic stem cell transplant (HSCT), mainly autologous, has been successfully adopted to treat patients affected by severe/refractory ADs. In this context malnutrition has a detrimental impact on relapse, mortality, infection rate, engraftment, long-term survival, and prolongation of hospitalization. However, in this population, the management of nutrition should be improved since nutritional assessment is partially performed in routine clinical practice. A panel of nurses and physicians from the European Society for Blood and Marrow Transplantation (EBMT) reviewed all available evidence based on current literature and expert practices from centers with extensive experience in HSCT for ADs, on the nutritional management of ADs patients during HSCT procedure. In this context, adequate nutritional status predicts a better response to treatment and improves quality of life. Herein, a systematic and comprehensive monitoring of nutritional status before, during and after HSCT, with adequate nutritional support in the case of ADs patients, in addition to assessing the dietary requirements associated with HSCT has been covered. Moreover, given the singularity of each AD, the underlying disease should be considered for an appropriate approach. The management and evaluation of nutritional status must be carried out by a multidisciplinary team to assess the needs, monitor the effectiveness of each intervention, and prevent complications, especially in complex situations as patients affected by ADs.

Biologic therapy is an effective treatment for inflammatory bowel disease [IBD]. However due to cost and safety concerns, dose de-escalation strategies after achieving remission have been suggested.

To critically review available data on dose de-escalation of biologics [or other advanced therapies] in IBD. We will focus on studies evaluating de-escalation to standard dosing in patients initially optimised, and also on studies assessing de-escalation from standard dosing.

A systematic bibliographic search was performed.

The mean frequency of de-escalation after previous dose intensification [12 studies, 1,474 patients] was 34%. The corresponding frequency of de-escalation from standard dosing [five studies, 3,842 patients] was 4.2%. The relapse rate of IBD following anti-tumour necrosis factor [TNF] de-escalation to standard dosing in patients initially dose-escalated [10 studies, 301 patients] was 30%. The corresponding relapse rate following anti-TNF de-escalation from standard dosing [nine studies, 494 patients] was 38%. The risk of relapse was lower for patients in clinical, biologic, and endoscopic/radiological remission at the time of de-escalation. A role of anti-TNF therapeutic drug monitoring in the decision to dose de-escalate has been demonstrated. In patients relapsing after de-escalation, re-escalation is generally effective. De-escalation is not consistently associated with a better safety profile. The cost-effectiveness of the de-escalation strategy remains uncertain. Finally, there is not enough evidence to recommend dose de-escalation of biologics different from anti-TNFs or small molecules.

Any consideration for de-escalation of biologic therapy in IBD must be tailored, taking into account the risks and consequences of a flare and patients' preferences.

A previous controlled trial of autologous haematopoietic stem-cell transplantation (HSCT) in patients with refractory Crohn's disease did not meet its primary endpoint and reported high toxicity. We aimed to assess the safety and efficacy of HSCT with an immune-ablative regimen of reduced intensity versus standard of care in this patient population.

This open-label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18-60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease [SES-CD] ulcer sub-score of ≥2) refractory to two or more classes of biological therapy, with no perianal or intra-abdominal sepsis or clinically significant comorbidity, were recruited. Participants were centrally randomly assigned (2:1) to either HSCT with a reduced dose of cyclophosphamide (intervention group) or standard care (control group). Randomisation was stratified by trial site by use of random permuted blocks of size 3 and 6. Patients in the intervention group underwent stem-cell mobilisation (cyclophosphamide 1 g/m2 with granulocyte colony-stimulating factor (G-CSF) 5 μg/kg) and stem-cell harvest (minimum 2·0 × 106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin [thymoglobulin] 7·5 mg/kg in total) and subsequent stem-cell reinfusion supported by G-CSF. Patients in the control group continued any available conventional, biological, or nutritional therapy. The primary outcome was absence of endoscopic ulceration (SES-CD ulcer sub-score of 0) without surgery or death at week 48, analysed in the intention-to-treat population by central reading. This trial is registered with the ISRCTN registry, 17160440.

Between Oct 18, 2018, and Nov 8, 2019, 49 patients were screened for eligibility, of whom 23 (47%) were randomly assigned: 13 (57%) to the intervention group and ten (43%) to the control group. In the intervention group, ten (77%) participants underwent HSCT and nine (69%) reached 48-week follow-up; in the control group, nine (90%) reached 48-week follow-up. The trial was halted in response to nine reported suspected unexpected serious adverse reactions in six (46%) patients in the intervention group, including renal failure due to proven thrombotic microangiopathy in three participants and one death due to pulmonary veno-occlusive disease. At week 48, absence of endoscopic ulceration without surgery or death was reported in three (43%) of seven participants in the intervention group and in none of six participants in the control group with available data. Serious adverse events were more frequent in the intervention group (38 in 13 [100%] patients) than in the control group (16 in four [40%] patients). A second patient in the intervention group died after week 48 of respiratory and renal failure.

Although HSCT with an immune-ablative regimen of reduced intensity decreased endoscopic disease activity, significant adverse events deem this regimen unsuitable for future clinical use in patients with refractory Crohn's disease.

Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

Inflammatory bowel disease (IBD) has a high economic burden due to its chronicity. Treatment has evolved, thanks to the understanding of IBD pathogenesis and the advent of biologic therapy, albeit the latter increases direct costs. The aim of the present study was to calculate the total cost and cost per patient/year of biologic therapy for IBD and IBD-associated arthropathy in Colombia.

A descriptive study was conducted. The data were obtained from the Comprehensive Social Protection Information System of the Department of Health for the year 2019, utilizing the medical diagnosis codes of the International Classification of Diseases related to IBD and IBD-associated arthropathy as keywords.

The prevalence of IBD and IBD-associated arthropathy was 61 cases per 100,000 inhabitants, with a female-to-male ratio of 1.5:1. Joint involvement was 3%, and 6.3% of the persons with IBD and IBD-associated arthropathy received biologic therapy. Adalimumab was the most widely prescribed biologic drug (49.2%). Biologic therapy had a cost of $15,926,302 USD and the mean cost per patient/year was $18,428 USD. Adalimumab had the highest impact on healthcare resource utilization, with a total cost of $7,672,320 USD. According to subtype, ulcerative colitis had the highest cost ($10,932,489 USD).

Biologic therapy is expensive, but its annual cost in Colombia is lower than that of other countries due to the government's regulation of high-cost medications.

Therapeutic drug monitoring provides important guidance for treatment of patients with inflammatory bowel disease (IBD) and could help to early identify treatment failure. This study aimed to validate a finger prick-based capillary blood sampling technique to measure biological trough levels and C-reactive protein (CRP) and evaluate patient performance and -support.

In this prospective cohort study, patients with IBD receiving infliximab (IFX) or vedolizumab (VEDO) therapy performed finger prick-based capillary blood sampling at home. Additionally, blood was collected through routinely performed in-hospital venepuncture prior to biological infusion. IFX, VEDO, and CRP concentrations were measured by enzyme-linked immunosorbent assay. The concordance between methods was statistically evaluated and a survey was conducted to assess practicality and patient support.

In total, 81 patients (46 IFX, 35 VEDO) were enrolled. Mean differences between both methods were 0.42 (95% confidence interval, -1.74 to 2.58) μg/mL for IFX and 0.72 (95% confidence interval, -5.50 to 6.94) μg/mL for VEDO. Passing-Bablok regressions demonstrated no evidence for systematic or proportional biases. Venous and capillary IFX (ρ = 0.96, P < .001) and VEDO (ρ = 0.97, P < .001) levels strongly correlated and showed high intermethod agreement (Cohen's kappa: IFX = 0.82; VEDO = 0.94). Similarly, venous and capillary CRP levels were strongly correlated (ρ = 0.99, P < .001). Most patients (>95%) were able to successfully perform the self-sampling at home without prior instructions.

This study clinically validated a finger prick-based capillary blood self-sampling technique allowing concomitant home monitoring of biological levels and CRP for patients with IBD, who reported substantial support, tolerability, and practicality.

The therapeutic armamentarium for managing Crohn's disease (CD) has expanded significantly in recent decades. Several biologics with three different mechanisms of action [anti-tumor necrosis factor (TNF)-α, anti-integrin α4β7, and anti-IL 12/23] are currently available to manage CD.

This narrative review aims to summarize the most significant efficacy and safety data on the use of infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ) and ustekinumab (UST) for the treatment of CD obtained from studies conducted in the real world (RW), compared to the results of randomized clinical trials (RCTs).

RW studies reported that biologic agents included in this analysis have higher remission rates and lower adverse event rates than findings from RCTs for treating patients with CD. All biological agents have proven effective and safe in RW studies, even when using biosimilars or switching to subcutaneous administration of the molecules for which they are available. Finally, anti-TNF-α agents, particularly IFX, have a higher rate of adverse events (AEs) than VDZ and UST. Therefore, patients at higher risk of AEs may benefit from other biologics than anti-TNF-α. However, further long-term RW studies are needed to confirm these findings.

Inflammatory bowel disease (IBD) has a major economic impact on healthcare costs.

The aim of this study was to evaluate the current healthcare expenditure associated with IBD in a population-wide study in Catalonia.

Retrospective observational study.

All patients with IBD included in the Catalan Health Surveillance System (CHSS) were considered eligible. The CHSS compiles data on more than 7 million individuals in 2020 (34,823 with IBD). Data on the use of healthcare resources and its economic impact were extracted applying the International Classification of Diseases, 10th revision, Clinical Modification codes (ICD-10-CM codes). Health expenditure, comorbidities, and hospitalization were calculated according to the standard costs of each service provided by the Department of Health of the Catalan government. The data on the IBD population were compared with non-IBD population adjusted for age, sex, and income level. IBD costs were recorded separately for Crohn's disease (CD) and ulcerative colitis (UC).

Prevalence of comorbidities was higher in patients with IBD than in those without. The risk of hospitalization was twice as high in the IBD population. The overall healthcare expenditure on IBD patients amounted to 164M€. The pharmacy cost represents the 60%. The average annual per capita expenditure on IBD patients was more than 3.4-fold higher (IBD 4200€, non-IBD 1200€). Average costs of UC were 3400€ and 5700€ for CD.

The risk of comorbidities was twice as high in patients with IBD and their use of healthcare resources was also higher than that of their non-IBD counterparts. Per capita healthcare expenditure was approximately 3.4 times higher in the population with IBD.

The study was not previously registered.

The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk.

A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis.

In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%.

This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.

We aimed to evaluate clinical efficacy, biomarker activity, therapeutic drug monitoring (TDM), adverse events (AEs), and nocebo effect in inflammatory bowel disease (IBD) patients who underwent non-medical biosimilar switching.

A prospective observational study of consecutive IBD patients who underwent biosimilar switch. Disease activity, biomarkers, TDM, and AEs, including the nocebo effect were captured 8 weeks before switch, at the time of switch (baseline),12 and 24 weeks after the switch.

210 patients were included [81.4% had Crohn's disease (CD), the median age at inclusion: 42 years (IQR 29-61)]. There was no significant difference in the rates of clinical remission at week 8 before switch, baseline, week12, and 24 after switch: 89.0%,93.4%,86.3%,and 90.8%,p = 0.129. The biomarker remission rates were not significantly different; CRP:81.3%,74.7%,81.2%,73.0%,p = 0.343; fecal calprotectin: 78.3%,74.5%,71.7%,76.3%,p = 0.829. The rates of maintaining therapeutic levels (84.7%,83.9%,83.0%,85.3%,p = 0.597) and prevalence of positive anti-drug antibodies remained unchanged. Drug persistence at 12 week of switch was 97.1%, regardless of disease phenotype and originator. The nocebo effect was observed in 13.3%. The discontinuation rate was 4.8%.

Despite a significant number of early nocebo complaints within the first 6 months after the biosimilar switch, no significant changes were found in clinical efficacy, biomarkers, therapeutic drug level, or anti-drug antibodies.

Inflammatory bowel disease (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases causing a lifelong burden and often need sustained treatment throughout a patient's life. Both the incidence and prevalence of IBD has increased in the last decade. Evidence showing the drug costs to IBD patients in Finland is limited. No earlier study has evaluated the drug costs of IBD patients in Finland. Here, we thoroughly assessed these costs.

A structured questionnaire, hospital records and national registers were combined to comprehensively assess the actual costs of drug purchases made by IBD patients. The study sample comprised 561 patients.

Total annual mean drug costs were 1428€ per patient. CD patients had higher annual costs than UC patients at 2369€ and 902€, respectively. CD patients also had higher costs in the immunosuppressant, corticosteroid, and biologic subgroup analyses. In addition, C-reactive protein, serum albumin and fecal calprotectin levels had a correlation with costs if the patient had needed corticosteroids. In addition, women reported having a worse quality of life (QoL) but had lower total costs.

Pharmaceutical drugs are major factors that affect the costs of IBD treatment, and the increased use of biologics has raised these costs.

Withdrawal of immunomodulators (IMMs) or tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel diseases (IBDs) in remission on combination therapy is attractive. We evaluated the efficacy and safety of (1) IMM, or (2) TNF antagonist withdrawal in patients with IBD in sustained remission on combination therapy.

Through a systematic review till March 31, 2023, we identified randomized controlled trials (RCTs) that compared the efficacy and safety of IMM or TNF antagonist withdrawal vs continued combination therapy, in patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy. Primary outcome was risk of relapse and serious adverse events at 12 months. We conducted meta-analysis to calculate relative risk (RR) and 95% confidence interval (CI) and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to appraise certainty of evidence.

We identified 8 RCTs with 733 patients (77% with Crohn's disease, 91% on infliximab-based combination therapy). On meta-analysis of 5 RCTs, there was no difference in the risk of relapse between patients with IMM withdrawal (continued TNF antagonist monotherapy) vs continued combination therapy (16.8% vs 14.9%; RR, 1.15; 95% CI, 0.75-1.76) without heterogeneity (low certainty of evidence). TNF antagonist withdrawal (continued IMM monotherapy) was associated with 2.4-times higher risk of relapse compared with continuing combination therapy (31.5% vs 11.2%; RR, 2.35; 95% CI, 1.38-4.01), with minimal heterogeneity (low certainty of evidence). There was no difference in the risk of serious adverse events with IMM or TNF antagonist withdrawal vs continued combination therapy.

In patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy, de-escalation with TNF antagonist withdrawal, but not IMM withdrawal, was associated with an increased risk of relapse.

Few population-based studies have investigated long-term surgery rates for Crohn's disease [CD]. Our aim was to analyse disease progression and surgery rates in a population-based cohort over different therapeutic eras, based on the time of diagnosis: cohort-A [1977-1995], cohort-B [1996-2008], and cohort-C [2009-2018].

A total of 946 incident CD patients were analysed (male/female: 496/450; median age at diagnosis: 28 years [y]; interquartile range [IQR]: 22-40]). Patient inclusion lasted between 1977 and 2018. Immunomodulators have become widespread in Hungary since the mid-1990s and biologic therapies since 2008. Patients were followed prospectively, with both in-hospital and outpatient records reviewed regularly.

The probability of disease behaviour progression from inflammatory [B1] to stenosing or penetrating phenotype [B2/B3] significantly decreased (27.1 ± 5.3%/21.5 ± 2.5%/11.3 ± 2.2% in cohorts A/B/C, respectively, after 5 years; 44.3 ± 5.9%/30.6 ± 2.8%/16.1 ± 2.9% after 10 years, respectively; [pLogRank <0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3 ± 3.8%/26.5 ± 2.1%/28.1 ± 2.4%, respectively, after 5 years; 46.1 ± 4.1%/32.6 ± 2.2%/33.0 ± 2.7% after 10 years, respectively; and 59.1 ± 4.0%/41.4 ± 2.6% [cohorts A/B] after 20 years. There was a significant decrease in first resective surgery risk between cohorts A and B [plog rank = 0.002]; however, no further decrease between cohorts B and C [plog rank = 0.665]. The cumulative probability of re-resection in cohorts A/B/C was decreasing over time (17.3 ± 4.1%/12.6 ± 2.6%/4.7 ± 2.0%, respectively, after 5 years [plog rank = 0.001]).

We report a continuous decline in reoperation rates and disease behaviour progression in CD over time, with the lowest values in the biologic era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era.

An estimated 2.5-3 million individuals (0.4%) in Europe are affected by inflammatory bowel disease (IBD). Whilst incidence rates for IBD are stabilising across Europe, the prevalence is rising and subsequently resulting in a significant cost to the healthcare system of an estimated 4.6-5.6 billion euros per year. Hospitalisation and surgical resection rates are generally on a downward trend, which is contrary to the rising cost of novel medication. This signifies a large part of healthcare cost and burden. Despite publicly funded healthcare systems in most European countries, there is still wide variation in how patients receive and/or pay for biologic medication. This review will provide an overview and discuss the different healthcare systems within Western Europe and the barriers that affect overall management of a changing IBD landscape, including differences to hospitalisation and surgical rates, access to medication and clinical trial participation and recruitment. This review will also discuss the importance of standardising IBD management to attain high-quality care for all patients with IBD.

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.

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.

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.

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.

ClinicalTrials.gov, number NCT03172377.

Inflammatory bowel diseases (IBDs) are chronic illnesses with significant morbidities and impact on patients' quality of life. There has been a rapid increase in the incidence of IBD in East Asia in recent decades. However, there is a huge unmet need in the diagnosis and management of IBD in this region. With the increasing awareness of IBD in East Asia and a persistently high rate of tuberculosis in this region, this poses a significant challenge in the diagnosis and management of IBD. In this review, we will explore the barriers to the diagnosis and management of IBD in the East Asia, hoping to provide an insight on how to improve the healthcare system in the management of this complex disease.

New Zealand (NZ) has one of the world's highest rates of inflammatory bowel diseases (IBD), however available data are limited to southern, urban regions.

To determine the incidence and prevalence of IBD in the Manawatū region of NZ.

Patients in the Manawatū region, with a diagnosis of IBD made between 2011 and 2015 were identified. Demographic, diagnostic and disease data were collected, fulfilment of diagnostic criteria was assessed, and incidence rates were calculated. Comparison of disease phenotype and observed diagnostic criteria was made between diagnosis and 12-months following diagnosis. All resident patients with a diagnosis of IBD current on 5 March 2013 were identified, and prevalence rates were calculated.

The mean annual age-standardised incidence rates of UC, CD, and IBD were 10.2, 17.0, and 27.2 per 100,000. IBD incidence was highest among those of European ethnicity (24.8 per 100,000), followed by Asian (1.4), and Māori (1.1). IBD incidence in the urban population was 34.0 per 100,000 (95% CI 24.1-46.0) compared to the rural population of 5.6 (95% CI 0.4-22.4). The age-standardised point prevalence of UC, CD, and IBD on 5 March 2013 was 157.7, 231.8, and 397.9 per 100,000, respectively.

The incidence and prevalence of IBD in the Manawatū region are comparable to those reported in other Australasian studies. Incidence was lower in Māori, and in the rural population. Follow-up is required to identify any changes in incidence and phenotype, and whether rural residence remains protective.