The corticosteroid-sparing effects of ileocaecal resection have not been thoroughly investigated in a population-based cohort.

To investigate systemic corticosteroid use before and after primary ileocaecal resection in patients with Crohn's disease.

Through nationwide registries, we identified 1565 patients with Crohn's disease undergoing primary ileocaecal resection in Sweden 2006-2019. We stratified patients according to mean annual systemic corticosteroid (prednisolone equivalents) use in the last 5 years before surgery and compared Crohn's disease treatment after surgery.

Some 19% (290/1565) of the patients had a mean annual corticosteroid use of ≥ 1000 mg up to 5 years pre-operatively, of whom 33% (97/290) had ≥ 2000 mg. Mean annual pre-operative CS use did not decrease during the study period (p = 0.35). Compared with patients with < 1000 mg/year pre-operative steroid use, patients with ≥ 1000 mg/year had more frequent previous bowel surgery (10% vs. 16%), exposure to biologics (29% vs. 38%), and immunomodulators (56% vs. 83%). Patients with a pre-operative mean annual corticosteroid use of ≥ 1000 mg had a mean annual reduction in corticosteroid use of 1354 mg after ileocaecal resection (1847 mg pre-operative versus 493 mg post-operative). During follow-up (median 6.8 years), exposure to biologics was similar among patients with different levels of pre-operative corticosteroid use.

Our results suggest a significant corticosteroid-sparing effect of ileocaecal resection in Crohn's disease patients with high pre-operative use, indicating a beneficial outcome of earlier surgical intervention. Despite increasing use of biologics, pre-operative corticosteroid use was consistent over the study period.

Psoriasis, a common chronic inflammatory skin disorder, encompasses various subtypes, including guttate, pustular, erythrodermic, and the most common type, plaque psoriasis. Irrespective of the subtype, psoriasis can manifest with multisystemic presentations, including psoriatic arthritis, metabolic disorders, cardiovascular disease, malignancies, chronic kidney disease (CKD), psychiatric illness, and inflammatory bowel disease (IBD). Many comorbidities and concomitant conditions must be considered when selecting the most appropriate therapy for a patient (Kaushik et al., 2019 and Monks et al., 2021) . Ongoing clinical trials and the development of new therapeutic targets contribute to the continuous improvement of available treatment options. Given the dynamic landscape of therapies, particularly when managing complex patients with multiple comorbidities, dermatologists are constantly challenged with the task of adeptly tailoring treatments to each psoriasis patient. This article systematically reviews the current evidence, presenting it as an updated Psoriasis Decision Tree to assist physicians in selecting tailored treatment options.

The objective of this study is to segment creeping fat and intestinal wall on computed tomography enterography (CTE) and develop a radiomic model to predict 1-year surgery risk in patients with Crohn's disease.

This retrospective study included 135 Crohn's disease patients who underwent CTE between January and December 2021 (training cohort) and 69 patients between January and June 2022 (test cohort). A total of 1874 radiomic features were extracted from the intestinal wall and creeping fat respectively on the venous phase CTE images, and radiomic models were constructed based on the selected features using the Boruta and extreme gradient boosting algorithms. The combined models were established by integrating clinical predictors and radiomic models. The receiver operating characteristic curve, calibration curve, and decision curve analyses were used to compare the predictive performance of models.

In the training and test cohorts, the area under the curve (AUC) values of the creeping fat radiomic model for surgery risk stratification were 0.916 and 0.822, respectively, similar to the intestinal model with AUC values of 0.889 and 0.822. Moreover, the combined radiomic model was superior to the single models, showing good discrimination with the highest AUC values (training cohort: 0.963; test cohort: 0.882). Addition of clinical predictors to the radiomic models failed to significantly improve the diagnostic ability.

The CTE-based creeping fat radiomic model provided additional information to the intestinal radiomic model, and their combined radiomic model enables accurate surgery risk prediction of Crohn's disease patients within 1 year of CTE.

We evaluated the association between endoscopic outcomes following risankizumab induction and subsequent rates of hospitalization and surgery through 52 weeks of risankizumab (both doses) maintenance therapy in patients with Crohn's disease (CD).

Patients with moderately to severely active CD and clinical response to 12-week risankizumab induction were rerandomized to continued therapy or drug withdrawal in the phase 3 FORTIFY maintenance trial. Incidence rates (events/100 person-years) of CD-related hospitalization and surgery, and the composite of both, through 52 weeks of maintenance were compared between patients achieving vs not achieving predefined endoscopic outcomes following induction.

Patients who achieved vs did not achieve endoscopic response or remission, or absence of ulcers (ulcer-free endoscopy) after induction had reduced rates of CD-related hospitalization through 52 weeks of risankizumab maintenance (endoscopic response, 1.7 vs 7.9/100 person-years; endoscopic remission, 1.2 vs 6.9/100 person-years; ulcer-free endoscopy, 1.5 vs 6.4/100 person-years; all P < .05). No CD-related surgeries were observed through 52 weeks of risankizumab maintenance among patients who achieved vs did not achieve endoscopic outcomes following induction (endoscopic response, 0 vs 3.2/100 person-years; endoscopic remission, 0 vs 2.6/100 person-years; ulcer-free endoscopy, 0 vs 2.4/100 person-years; all P = .025). In contrast, patients who received placebo during maintenance had statistically similar rates of CD-related hospitalizations and surgeries regardless of achievement of endoscopic outcomes after induction.

Patients achieving endoscopic outcomes following risankizumab induction experienced less CD-related hospitalizations and surgeries through 52 weeks of maintenance when continuing active therapy. Early treatment success may predict favorable long-term outcomes of disease.

ADVANCE (NCT03105128); MOTIVATE (NCT03104413) and FORTIFY (NCT03105102).

Limited knowledge exists regarding the optimal timing and relative advantages of primary surgery compared to medical treatment in ileocecal Crohn's disease (CD). This study aimed to compare long-term outcomes between medication-based treatment versus surgery in newly diagnosed ileocecal CD patients in an Asian population.

Among the 885 patients diagnosed with CD and enrolled in the study site hospital cohort between 1980 and 2013, 93 (10.5%) had ileocecal CD. Patients were categorized into either the surgical or medical remission group based on their initial management strategy that led to remission. The rates of relapse, hospitalization, and surgery after achieving remission were compared using Kaplan-Meier curves.

The numbers of patients assigned to surgical and medical remission groups were 15 (17.0%) and 73 (83.0%), respectively. The surgical remission group exhibited a lower relapse rate and longer maintenance of remission (10.7 vs. 3.7 yr; p = 0.017) during a median follow-up of 6.6 years. Hospitalization after the first remission tended to be lower in the surgical remission group (p = 0.054). No cases required repeated intestinal resection after the initial surgical remission, whereas a 23% surgery rate was reported at 5 years after initial medical treatment (p = 0.037). In the multivariable analysis, the initial medication-based treatment was significantly associated with relapse (hazard ratio = 3.23, p = 0.039).

In selected cases of localized ileocecal CD, ileocolic resection might be a favorable alternative to medication- based treatment, as it demonstrates a lower relapse rate and longer maintenance of remission.

Data regarding the worldwide gastrointestinal surgery rates in patients with Crohn's disease (CD) remains limited.

To systematically review the global variation in the rates of surgery in CD.

A comprehensive search analysis was performed using multiple electronic databases from inception through July 1, 2020, to identify all full text, randomized controlled trials and cohort studies pertaining to gastrointestinal surgery rates in adult patients with CD. Outcomes included continent based demographic data, CD surgery rates over time, as well as the geoepidemiologic variation in CD surgery rates. Statistical analyses were conducted using R.

Twenty-three studies spanning four continents were included. The median proportion of persons with CD who underwent gastrointestinal surgery in studies from North America, Europe, Asia, and Oceania were 30% (range: 1.7%-62.0%), 40% (range: 0.6%-74.0%), 17% (range: 16.0%-43.0%), and 38% respectively. No clear association was found regarding the proportion of patients undergoing gastrointestinal surgery over time in North America (R 2 = 0.035) and Europe (R 2 = 0.100). A moderate, negative association was seen regarding the proportion of patients undergoing gastrointestinal surgery over time (R 2 = 0.520) in Asia.

There appears to be significant inter-continental variation regarding surgery rates in CD. Homogenous evidence-based guidelines accounting for the geographic differences in managing patients with CD is prudent. Moreover, as a paucity of data on surgery rates in CD exists outside the North American and European continents, future studies, particularly in less studied locales, are warranted.

Corticosteroids are recommended only for induction of remission in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). This study aimed to evaluate the change in pharmacologic treatment use, particularly systemic corticosteroids, over approximately 30 years, and the impact of biologics on IBD treatment since their appearance in the 2000s.

This retrospective study conducted in Japan used data from the Phoenix cohort database (January 1990 to March 2021). Patients with disease onset at age ≥ 10 years who received treatment for UC or CD between January 1990 and March 2021 were included. Outcome measures were change in IBD treatments used, total cumulative corticosteroid doses, initial corticosteroid dose, duration of corticosteroid treatment, and surgery rate.

A total of 1066 and 579 patients with UC and CD, respectively, were included. In UC, the rate of corticosteroid use as initial treatment was relatively stable regardless of the year of disease onset; however, in CD, its rate decreased in patients who had disease onset after 2006 (before 2006: 14.3-27.8% vs. after 2006: 6.6-10.5%). Compared with patients with disease onset before biologics became available, cumulative corticosteroid doses in both UC and CD, and the surgery rate in CD only, were lower in those with disease onset after biologics became available.

Since biologics became available, corticosteroid use appears to have decreased, with more appropriate use. Furthermore, use of biologics may reduce surgery rates, particularly in patients with CD. UMIN Clinical Trials Registry; UMIN000035384.

Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies.

PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP >upper limit of normal or faecal calprotectin ≥200 μg/g, or both), while remission was the converse-ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 μg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228).

Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0-191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker-treatment interaction effect (absolute difference 1 percentage points, 95% CI -15 to 15; p=0·944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p<0·0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infections (three vs eight).

Top-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease.

Wellcome and PredictImmune Ltd.

There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression.

We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively.

A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792).

Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

Biologics, a mainstay in inflammatory bowel disease (IBD) treatment, typically require prior authorization from insurance companies. Multiple studies show that African Americans are less likely to be prescribed biologics. The prior authorization process may perpetuate disparities in healthcare. This study evaluated the approval time for biologics in IBD.

A chart review of IBD patients seen in a university gastroenterology clinic over 5 years was performed. Patient gender, race, IBD subtype, biologic use, and insurance type were recorded. Insurance type was classified as private or public (Medicaid or Medicare). Biologic agents evaluated included infliximab, adalimumab, vedolizumab and ustekinumab. Length of time to approval (TTA) and length of time to first infusion or administration (TFI) were recorded. Analysis was performed using t-testing, Fisher's exact testing, and ANOVA with significance set at p<0.05. The study was IRB approved.

458 charts were analyzed. 66 patients were being treated with a biologic. 42 had private insurance, 16 Medicaid and 8 Medicare. 37 patients had ulcerative colitis, 27 Crohn's disease, and 2 indeterminate colitis. There were 38 men and 28 women. 32 patients were white, 26 African American, 1 Asian, 5 other, and 2 declined identification. Average TTA was 30.5 days (range 1-145) and average TFI was 45.3 days (range 2-166). African Americans were more often on public insurance compared to whites (p=0.0001). Crohn's disease compared to ulcerative colitis patients were more often on public insurance (p=0.017). Significantly more private compared to public insurance patients were on infliximab (p=0.001). Medicaid and Medicare patients had significantly longer mean TTAs than private insurance patients (49.1 and 52.7 vs 19.4 days, p=0.007). African Americans had significantly longer mean TTA compared to whites (45.9 vs 24.8 days, p=0.044). Crohn's disease compared to ulcerative colitis patients had significantly longer mean TTA (39.7 vs 21.8 days, p=0.050).

This study shows that prior authorization for biologic therapy was longer for African Americans. Patients on public insurance also tend to have a longer TTA, and more African Americans were on public insurance compared to White patients in this study which may explain the difference in biologic access for African Americans.

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.

Cancer is a major cause of morbidity and mortality among people with inflammatory bowel disease (IBD). Intestinal cancers may arise as a complication of IBD itself, while extra-intestinal cancers may arise due to some of the immunosuppressive therapies used to treat IBD. Colorectal cancer (CRC) and small bowel cancer risks remain elevated among persons with IBD as compared to age-and sex-matched members of the general population, and the lifetime risk of these cancers is strongly correlated to cumulative intestinal inflammatory burden. However, the cumulative risk of cancer, even among those with IBD is still low. Some studies suggest that IBD-CRC incidence has declined over the years, possibly owing to improved treatment standards and improved detection and management of early neoplastic lesions. Across studies of extra-intestinal cancers, there are generally higher incidences of melanoma, hepatobiliary cancer, and lung cancer and no higher incidences of breast cancer or prostate cancer, with equivocal risk of cervical cancer, among persons with IBD. While the relative risks of some extra-intestinal cancers are increased with treatment, the absolute risks of these cancers remain low and the decision to forego treatment in light of these risks should be carefully weighed against the increased risks of intestinal cancers and other disease-related complications with undertreated inflammatory disease. Quality improvement efforts should focus on optimized surveillance of cancers for which surveillance strategies exist (colorectal cancer, hepatobiliary cancer, cervical cancers, and skin cancers) and the development of cost-effective surveillance strategies for less common cancers associated with IBD.

Psoriasis is a chronic, inflammatory, multisystemic disease which affects approximately 2-3% of the population globally, whose onset is triggered by genetic and environmental factors which activate both dendritic cells and keratinocytes, resulting in the production of proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 17, interleukin 23, interleukin 22, and interleukin 1β. An in-depth understanding of the pathophysiology of psoriasis led to significant advances in the development of safe and efficient novel therapeutic options, with four classes of biologic therapy being approved for the management of moderate to severe psoriasis: tumor necrosis factor alpha inhibitors, interleukin 23 inhibitors, anti-interleukin 12/23 agents, anti-interleukin 17 agents, as well as small-molecule inhibitors, such as apremilast. Psoriasis is associated with comorbid conditions, namely psoriatic arthritis, cardiovascular disease, metabolic syndrome, psychiatric disorders, malignancy, as well as inflammatory bowel disease. For patients affected by both psoriasis and inflammatory bowel disease, there is a strong recommendation to avoid IL-17 inhibitors since they may play a part in the exacerbation of the gastrointestinal disease. Our aim was to perform a thorough literature review regarding the development of inflammatory bowel disease lesions in psoriasis patients treated with IL-17 inhibitors, along with a case presentation to emphasize the need for close follow-up of these patients.

Stenosis, fistulization, and perforation of the bowel are severe outcomes which can occur in patients with Crohn's disease. Accurate prediction of these events may enable clinicians to alter treatment strategies and avoid these outcomes.

To study the correlation between longitudinal laboratory testing and subsequent intestinal complications in patients with Crohn's disease.

An observational cohort of patients with Crohn's disease at a single center were analyzed between 01/01/1994 and 06/30/2016. A complication was defined as the development of an intestinal fistula, stenosis, or perforation. Exploratory analysis using Cox regression was performed to select the best statistical method to represent longitudinal laboratory data. Cox regression was used to identify laboratory variables independently associated with the development of a subsequent complication. A clinical scoring tool was designed.

In 246 patients observed over a median of 5.72 years, 134 complications occurred. Minimum or maximum value in a preceding window period of one year was most strongly associated with subsequent complication. A Longitudinal Laboratory score of ≥ 2 (maximum albumin level < 39 g/L = 1, maximum mean cell volume < 88 fL = 1, minimum platelet count > 355 × 10⁹/L = 1, minimum C reactive protein > 5 mg/L = 1) was 62% sensitive and 91% specific in identifying patients who develop a subsequent complication.

A consistent reduction in serum albumin and mean cell volume, and a consistent increase in platelet count and C reactive protein were associated with a subsequent complication in patients with Crohn's disease. Longitudinal laboratory tests may be used as described in this paper to provide a rational for earlier escalation of therapy.

Psoriasis is a systemic immune-mediated disease associated with an increased risk of comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel disease, psychiatric disorders, and malignancy. In recent years, with the advent of biological agents, the efficacy and safety of psoriasis treatments have dramatically improved. Presently, tumor necrosis factor-α inhibitors, interleukin-17 inhibitors, interleukin-12/23 inhibitors, and interleukin-23 inhibitors are approved to treat moderate-to-severe psoriasis. Small-molecule inhibitors, such as apremilast and deucravacitinib, are also approved for the treatment of psoriasis. Although it is still unclear, systemic agents used to treat psoriasis also have a significant impact on its comorbidities by altering the systemic inflammatory state. Data from clinical trials and studies on the safety and efficacy of biologics and small-molecule inhibitors provide important information for the personalized care and treatment for patients with psoriasis. Notably, treatment with interleukin-17 inhibitors is associated with new-onset or exacerbations of inflammatory bowel disease. In addition, great caution needs to be taken when using tumor necrosis factor-α inhibitors in patients with psoriasis with concomitant congestive heart failure, multiple sclerosis, and malignancy. Apremilast may induce weight loss as an adverse effect, presenting also with some beneficial metabolic actions. A better understanding of the characteristics of biologics and small-molecule inhibitors in the treatment of psoriasis comorbidities can provide more definitive guidance for patients with distinct comorbidities.

Inflammatory bowel disease (IBD) is a chronic immune-mediated intestinal disease consisting of ulcerative colitis and Crohn's disease. Inflammatory bowel disease is believed to be developed as a result of interactions between environmental, immune-mediated and microbial factors in a genetically susceptible host. Recent advances in high-throughput sequencing technologies have aided the identification of consistent alterations of the gut microbiome in patients with IBD. Preclinical and murine models have also shed light on the role of beneficial and pathogenic bacteria in IBD. These findings have stimulated interest in development of non-invasive microbial and metabolite biomarkers for predicting disease risk, disease progression, recurrence after surgery and responses to therapeutics. This review briefly summarizes the current evidence on the role of gut microbiome in IBD pathogenesis and mainly discusses the latest literature on the utilization of potential microbial biomarkers in disease diagnosis and prognosis.

Long term outcomes have been reported in home parenteral nutrition (HPN)-dependent patients with type 3 intestinal failure (IF), but there are limited survival data standardised to the general population that would help provide a meaningful prognosis for patients and clinicians. The primary aim of this study was therefore to investigate the survival of HPN-dependent patients and to evaluate the specific impact of type 3 IF on their life expectancy standardised to that of the general population.

This was a cohort study of adult patients initiated on HPN between 1978 and 2018 at a national UK IF reference centre and followed up until death or censoring date of 31st December 2020. The standardised mortality ratio (SMR) was calculated as observed deaths divided by expected deaths using UK Office for National Statistics database. Excess Life Years Lost (LYL) were calculated separately for each sex as the differences in average life expectancy between patients with type 3 IF and the general population. Survival data were evaluated using cox regression models adjusting for confounding.

In total, 1046 patients were identified, with a total observation time of 7344.1 patient-years. Patients with malignancy (n = 206) were excluded from the survival analysis. Of the remaining 840 patients, 398 were alive by the end of follow-up. The probability of survival was 91.8% at 1 year, 69.3% at 5 years, 54.3% at 10 years, 29.8% at 20 years and 16.7% at 30 years. Patients who did not achieve nutritional autonomy had an increased likelihood of death compared to patients who ceased HPN. In total, 40 (9.0%) deaths were HPN or IF-related, while underlying disease leading to IF accounted for 98 (22.2%) deaths. There were 270 (61.1%) deaths not related to IF, with the majority of these patients dying from infections unrelated to HPN. Overall mortality rates were higher among patients with a diagnosis of type 3 IF compared with the general UK population with a SMR of 7.48 (95% CI 6.80 to 8.21) and an excess mortality rate of 54.0 per 1000 person-years. All mechanisms of IF were associated with excess mortality, with SMR ranging from 6.82 (95% CI 5.98 to 7.72) for short bowel syndrome to 15.51 (95% CI 11.73 to 20.03) for dysmotility. On average, the excess LYL was 17.45 years for males and 17.39 years for females compared with the general population of the same age.

This the largest single-centre series reporting survival outcomes in patients with type 3 IF over more than a four-decade period and the first to report LYL in this patient cohort. Type 3 IF was associated with more than seven-fold higher mortality rates than for the general UK population and shorter life expectancies of more than 17 years. Survival, however, was better in those able to achieve nutritional autonomy. Since the majority of deaths were due to non-HPN or non-IF causes, there is clearly a need now to further explore these causes of death in order to improve our understanding of excessive mortality in type 3 IF and develop ways to prevent it.

Relapse is a problem in patients with Crohn's disease (CD) after medical therapy (including biologics) and after surgery to treat acute inflammation. It is unclear whether the recurrence rate over time is higher after surgical therapy than after continuous drug treatment.

We sought to compare clinical relapse rates and the need for re-interventions (resection or therapeutic endoscopic intervention) in patients with CD.

A meta-analysis was performed according to PRISMA guidelines.

The need for one of the three re-interventions (surgery, biologics or both) increased over time. The recurrence rates in patients after ileocecal resection were lower than the rates under biologic therapy. The odds ratio for clinical recurrence under biologics versus after surgical treatment was 2.50 (95% confidence interval [CI] 1.53-4.08, p-value < 0.001). The odds ratio for surgical recurrence under biologics versus after surgery was 3.60 (95% CI 1.06-12.3, p-value 0.041).

These findings support surgical resection as a treatment option in patients with CD with limited disease.

Anti-TNFα are recommended for preventing Crohn's disease (CD) postoperative recurrence (POR) in patients with risk factors. However, few data exploring anti-TNFα efficacy in patients with preoperative anti-TNFα failure are available so far.

The aim of the present study was to compare the efficacy of anti-TNFα with other biologics and immunosuppressants to prevent POR in this setting.

Consecutive CD patients who underwent bowel resection between January 2010 and December 2019 after failure of at least one anti-TNFα were retrospectively included among three tertiary centers if they started a postoperative medical prophylaxis within the three months after index surgery. The main outcome was to compare rates of objective recurrence (endoscopic or radiological recurrence in absence of colonoscopy) between patients treated with an anti-TNFα agent or another treatment as prevention of POR.

Among the 119 patients included, 71 patients received an anti-TNFα (26 infliximab, 45 adalimumab) and 48 another treatment (18 ustekinumab, 7 vedolizumab, 20 azathioprine and 3 methotrexate) to prevent POR. Rates of objective recurrence at two years were 23.9% in patients treated with anti-TNFα and 44.9% in the others (p = 0.011).

Anti-TNFα remained an effective option to prevent POR for patients operated upon with previous anti-TNFα failure.

Crohn's disease is a chronic inflammatory bowel disease that most commonly affects the ileum. As a result, it is associated with a high lifetime risk of one or more surgical resections. The surgical paradigm is to preserve intestinal length. This study aims to assess the length of ileum resected at the index operation and at subsequent ileocolic resections for Crohn's disease.

This is a retrospective study assessing the clinical and pathological data of patients undergoing ileocolic resection for the management of Crohn's disease over the period 01/01/2002 to 31/07/2020 in two metropolitan Australian hospitals.

One hundred and seventy-six patients were analysed: 130 underwent a single resection; 31 underwent two resections; and 15 underwent three resections. The median age at the first operation was 37.2 years (range 18-69) with 60% of patients female. The median length resected at the first surgery was 17.8 cm (IQR 12.0) for small bowel, and 5.0 cm (IQR 1.0) for large bowel. The length of ileum resected at the first surgery was significantly greater than that of the second (P = 0.0001), without significant differences between the second and third resections (P = 0.49). The time interval from diagnosis to the first surgery had no significant impact on the length of intestine resected at the index ileocolic resection.

In Crohn's disease, the length of ileum removed at first resection is the greatest, with subsequent resection lengths less than the first.

Surgery rates in patients with Crohn's disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohn's disease over time.

Through linkage of national registers, we identified patients who were diagnosed with Crohn's disease in 2003-2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003-2006, 2007-2010, and 2011-2014).

In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001).

Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohn's disease diagnosis has not decreased from 2003 to 2019.

Crohn's disease (CD) is associated with reduced quality of life, increased absenteeism and high direct medical costs resulting from frequent hospitalizations and surgeries. Tumor necrosis factor-alpha inhibitors (TNFi's) have transformed the therapeutic landscape and enabled a shift from a symptom control to a treat-to-target strategy. The Effect of Tight Control Management on Crohn's Disease (CALM) trial demonstrated tight control (TC), with TNFi dose changes informed by biochemical markers of inflammation, achieved higher mucosal healing rates compared with conventional management (CM) based on symptoms. A Markov model compared TC and CM strategies from the perspective of the Canadian public payer using patient-observation data from the CALM trial. A regression model estimated weekly CD Activity Index-based transition matrices over a 5-year horizon and included covariates to improve extrapolation of outcomes beyond the 48-week trial assessment period. Costs of CD-related hospitalizations, biomarker tests and adalimumab injections were sourced from public data. Other direct medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Absenteeism was monetized and included in a sensitivity analysis. Over the 5-year time horizon, TC reduced hospitalization costs by 64% compared with CM. Other direct medical costs were reduced by 22%; adalimumab costs increased by 38%, generating an ICER of $35,168 per QALY gained. Absenteeism costs were reduced by 54%, and, when that was included in the model, TC became dominant compared with CM. Management of CD with TC is cost-effective compared with CM in Canada and is dominant if indirect costs associated with absenteeism are included. Trial registration number: NCT01235689.

We compared real-world healthcare resource utilization (HRU), Crohn's disease (CD)-related complications, and time to systemic corticosteroid discontinuation between patients with CD treated with adalimumab versus vedolizumab as initial biologic.

Biologic-naïve adults with CD and ≥2 claims between 05/20/2014 and 09/30/2019 for adalimumab or vedolizumab were identified in the IBM MarketScan research database. Patient characteristics were assessed during the 6-month baseline period before biologic initiation (index date). Adalimumab- and vedolizumab-treated patients were propensity score-matched 1:1 on demographics, disease characteristics, and comorbidities with ≥10% prevalence that differed significantly between groups. Categorical, continuous, and time-to-event outcomes between groups during the 12-month follow-up on/after index were compared with chi-square tests, Wilcoxon rank-sum tests, and Kaplan-Meier analyses, respectively.

Adalimumab- and vedolizumab-treated patients were matched (n = 461 per group) and baseline characteristics balanced. Significantly fewer adalimumab- versus vedolizumab-treated patients had a CD-related emergency room visit (12-month proportion: 14.5% vs 21.0%; log-rank P < 0.01) or inpatient admission (14.9% vs 20.2%; log-rank P < 0.05). Rates of CD-related surgeries were similar (9.3% vs 11.5%; log-rank P = 0.282). Among patients without internal/perianal abscess or fistula or intestinal stricture at baseline (N ADA = 360, N VDZ = 364), numerically but not significantly fewer adalimumab- versus vedolizumab-treated patients had CD-related complications at 12 months (18.3% vs 22.3%; P = 0.171). Among patients with corticosteroid use at index (N ADA = 143, N VDZ = 139), significantly more adalimumab- versus vedolizumab-treated patients discontinued corticosteroids (12-month proportion: 90.2% vs 76.3%; log-rank P < 0.001).

Patients with CD treated with adalimumab as their first biologic experienced significantly lower CD-related HRU and were more likely to discontinue corticosteroids compared to vedolizumab-treated patients.

Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce.

We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita.

Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year.

The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.

Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it.

We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation.

We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09-1.46; p = 0.002).

Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more.

Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases, including Crohn's disease (CD).

This case report and narrative review demonstrate the potential safety of dual biologic therapy (DBT) in a 45-year-old female with two separate immune-mediated diseases. She had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab, and she had been recently diagnosed with CD after presenting with diarrhoea. The CD diagnosis was confirmed radiologically, endoscopically, histologically, and biochemically. The patient received treatment with vedolizumab, a gut-specific inhibitor of the α4β7 integrin on leukocytes. No adverse reactions were observed for the duration of treatment. The safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was demonstrated.

DBT may be a safe and effective option for the treatment of refractory disease or multiple immune-mediated diseases. Newer biologics, which have improved safety profiles and gut specificity, may provide promising avenues for treatment. However, caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties, side effects, and efficacy profiles. Current evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019, but treatment decisions should be made in a multidisciplinary setting. Further research from controlled trials is needed to better understand the safety profile of DBT in CD. The immunopathological mechanisms underlying DBT also remain to be clarified.

The deeper understanding of the inflammatory process which gradually evolves into irreversible fibrosis and tissue damage has provided a precise picture of the disease course of luminal ileocecal Crohn's disease. According to the model of progressive structural damage, ideal time windows for medical and surgical treatment have been identified. While complicated disease clearly profits from surgical treatment, uncomplicated disease has become, in the last years, the most debatable setting in terms of different approaches including early surgery. On one hand, the rationale of traditional escalating medical therapy (step-up approach) has been undermined by the top-down medical approach. Indeed, the step-up approach has the possible drawback of delaying, up to a later disease stage, the use of more effective agents such as anti-tumor necrosis factors. Conversely, the top-down approach might expose patients to an overtreatment along with side effects including hypersensitivity to biologic agents. More recently, it has been shown how early surgery could be a valid option in this subset of patients being more cost-effective than medical therapy. Involving the surgeon at an early stage is considered now a good clinical practice and, in this scenario full of possibilities, the surgeon should be included into the decision-making process from the very beginning of patient management.