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Chronic inflammatory diseases (CIDs) pose a growing healthcare challenge, with a substantial proportion of patients showing inadequate response to biological treatment. There is renewed interest in dietary changes to optimize treatment regimens, with a growing body of evidence suggesting beneficial effects with adherence to a gluten-free diet. This study compared the likelihood of achieving clinical response to biological treatment after 14-16 weeks in patients with CID with high versus low-to-medium gluten intake. Secondary outcomes of interest included changes in disease activity, health-related quality of life and C-reactive protein. The study was a multicentre prospective cohort of 193 participants with a CID diagnosis (i.e. Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis or Psoriasis) who initiated biological treatment between 2017 and 2020. Participants were stratified based on their habitual gluten intake: the upper 33.3% (high gluten intake) and the remaining 66.6% (low-to-medium gluten intake). The proportion of patients achieving clinical response to biological treatment after 14-16 weeks was compared using logistic regression models. The median gluten intake differed significantly between groups (12.5 g/day vs. 5.9 g/day, standardized mean difference = 1.399). In total, 108 (56%) achieved clinical response to treatment, with no difference between 35 (55%) in the high gluten group and 73 (57%) in the medium-to-low gluten group (OR = 0.96 [0.51-1.79], p = 0.897). No differences were found with secondary outcomes. In conclusion, this study found no association between gluten intake and response to biological treatment in patients with CID., (© 2024 The Author(s). Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144., (© 2024 The Author(s). Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

Background & Aims: Clostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting., Methods: This multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) 8 weeks after the last FMT treatment. Secondary outcomes included CDAD cure 1 and 8 weeks after the first FMT treatment and 90-day mortality following positive C. difficile test., Results: We included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range [IQR], 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%; 95% confidence interval [CI], 71%-79%) at week 1. At week 8, 255 patients (55%; 95% CI, 50%-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%; 95% CI, 75%-82%). The 90-day mortality was 10% (95% CI, 8%-14%)., Conclusion: Repeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival., Clinicaltrials: gov, Number: NCT03712722., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life., Methods: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance., Results: In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69-2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1-7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 μg/mL (range 0.005-0.12 μg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4-6.9] μg/mL) and without (3.1 [range 0.7-11.0] μg/mL) infections during the first year of life (P = .41)., Conclusions: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: The macrophage activation marker soluble (s)CD163 is associated with disease severity and prognosis in patients with primary biliary cholangitis (PBC). Ursodeoxycholic acid (UDCA) treatment attenuates fibrosis progression in PBC patients, but its effect on macrophage activation is unclear. We examined the effect of UDCA on macrophage activation, as determined by sCD163 levels., Methods: We included 2 cohorts of PBC patients; 1 cohort with prevalent PBC patients, and 1 cohort of incident PBC patients before start of UDCA treatment and with follow-up after 4 weeks and 6 months. We measured sCD163 and liver stiffness in both cohorts. Further, we measured sCD163 and TNF-α shedding in vitro in monocyte-derived macrophages after UDCA and lipopolysaccharide incubation., Results: We included 100 patients with prevalent PBC [93% women, median age 63 y (interquartile range: 51-70)] and 47 patients with incident PBC [77% women, median age 60 y (49-67)]. Prevalent PBC patients had a lower median sCD163 of 3.54 mg/L (2.77-4.72) than incident PBC patients with a median sCD163 of 4.33 mg/L (2.83-5.99) at inclusion. Patients with an incomplete response to UDCA and patients with cirrhosis had higher sCD163 than responders to UDCA and noncirrhosis patients. After 4 weeks and 6 months of UDCA treatment median sCD163 decreased by 4.6% and 9.0%, respectively. In in vitro experiments, UDCA attenuated shedding of TNF-α, but not sCD163, from monocyte-derived macrophages., Conclusion: In PBC patients, sCD163 levels correlated with liver disease severity and treatment response to UDCA. Further, after 6 months of UDCA treatment, we observed a decrease in sCD163, which may be related to the treatment., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Biologic disease-modifying drugs have revolutionised the treatment of a number of chronic inflammatory diseases (CID). However, up to 60% of the patients do not have a sufficient response to treatment and there is a need for optimization of treatment strategies., Objective: To investigate if the treatment outcome of biological therapy is associated with the habitual dietary intake of fibre and red/processed meat in patients with a CID., Methods: In this multicentre prospective cohort study, we consecutively enrolled 233 adult patients with a diagnosis of Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis (RA), Axial Spondyloarthritis, Psoriatic Arthritis and Psoriasis, for whom biologic therapy was planned, over a 3 year period. Patients with completed baseline food frequency questionnaires were stratified into a high fibre/low red and processed meat exposed group (HFLM) and an unexposed group (low fibre/high red and processed meat intake = LFHM). The primary outcome was the proportion of patients with a clinical response to biologic therapy after 14-16 weeks of treatment., Results: Of the 193 patients included in our primary analysis, 114 (59%) had a clinical response to biologic therapy. In the HFLM group ( N = 64), 41 (64%) patients responded to treatment compared to 73 (56%) in the LFHM group ( N = 129), but the difference was not statistically significant (OR: 1.48, 0.72-3.05). For RA patients however, HFLM diet was associated with a more likely clinical response (82% vs. 35%; OR: 9.84, 1.35-71.56)., Conclusion: Habitual HFLM intake did not affect the clinical response to biological treatment across CIDs. HFLM diet in RA patients might be associated with better odds for responding to biological treatment, but this would need confirmation in a randomised trial., Trial Registration: (clinicaltrials.gov), identifier [NCT03173144]., Competing Interests: Author CH has received speaker fee from Takeda Pharma and Tillotts Pharma (unrelated to the present work). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Overgaard, Sørensen, Munk, Nexøe, Glerup, Henriksen, Guldmann, Pedersen, Saboori, Hvid, Dahlerup, Hvas, Jawhara, Andersen, Pedersen, Nielsen, Bergenheim, Brodersen, Heitmann, Halldorsson, Holmskov, Bygum, Christensen, Kjeldsen, Ellingsen and Andersen.)

Introduction: Magnetic resonance enterography (MRE) is useful for detecting bowel strictures, whereas a number of imaging biomarkers may reflect severity of fibrosis burden in Crohn's disease (CD). This study aimed to verify the association of MRE metrics with histologic fibrosis independent of inflammation., Methods: This prospective European multicenter study performed MRE imaging on 60 patients with CD with bowel strictures before surgical resection. Locations of 61 histological samples were annotated on MRE examinations, followed by central readings using the Chiorean score and measurement of delayed gain of enhancement (DGE), magnetization transfer ratio, T2-weighted MRI sequences (T2R), apparent diffusion coefficient (ADC), and the magnetic resonance index of activity (MaRIA). Correlations of histology and MRE metrics were assessed. Least Absolute Shrinkage and Selection Operator and receiver operator characteristic (ROC) curve analyses were used to select composite MRE scores predictive of histology and to estimate their predictive value., Results: ADC and MaRIA correlated with fibrosis (R = -0.71, P < 0.0001, and 0.59, P < 0.001) and more moderately with inflammation (R = -0.35, P < 0.01, and R = 0.53, P < 0.001). Lower or no correlations of fibrosis or inflammation were found with DGE, magnetization transfer ratio, or T2R. Least Absolute Shrinkage and Selection Operator and ROC identified a composite score of MaRIA, ADC, and DGE as a very good predictor of histologic fibrosis (ROC area under the curve = 0.910). MaRIA alone was the best predictor of histologic inflammation with excellent performance in identifying active histologic inflammation (ROC area under the curve = 0.966)., Discussion: MRE-based scores for histologic fibrosis and inflammation may assist in the characterization of CD stenosis and enable development of fibrosis-targeted therapies and clinical treatment of stenotic patients., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aims: The health consequences of coronavirus disease 2019 [COVID-19] among patients with ulcerative colitis [UC] and Crohn's disease [CD] remain largely unknown. We aimed to investigate the outcomes and long-term effects of COVID-19 in patients with UC or CD., Methods: We conducted a prospective, population-based study covering all Danish patients with CD or UC and confirmed COVID-19 between January 28, 2020 and April 1, 2021, through medical records and questionnaires., Results: All 319 patients with UC and 197 patients with CD who developed COVID-19 in Denmark were included in this study and compared with the Danish background population with COVID-19 [N = 230 087]. A significantly higher risk of COVID-19-related hospitalization was observed among patients with UC (N = 46 [14.4%], relative risk [RR] = 2.49 [95% confidence interval, CI, 1.91-3.26]) and CD (N = 24 [12.2%], RR = 2.11 [95% CI 1.45-3.07]) as compared with the background population (N = 13 306 [5.8%]). A similar pattern was observed for admission to intensive care (UC: N = 8 [2.51%], RR = 27.88 [95% CI 13.88-56.00]; CD: N = 3 [1.52%], RR = 16.92 [95% CI 5.46-52.46]). After a median of 5.1 months (interquartile range [IQR] 4.5-7.9), 58 [42.3%] and 39 [45.9%] patients with UC and CD, respectively, reported persisting symptoms which were independently associated with discontinuation of immunosuppressive therapies during COVID-19 (odds ratio [OR] = 1.50 [95% CI 1.07-10.22], p = 0.01) and severe COVID-19 (OR = 2.76 [95% CI 1.05-3.90], p = 0.04), but not with age or presence of comorbidities., Conclusion: In this population-based study of 516 patients with IBD and COVID-19, 13.6% needed hospitalization and 2.1% required intensive care. Furthermore, sequelae were frequent, affecting 43.7% of COVID-19-infected patients. These findings might have implications for planning the healthcare of patients in the post-COVID-19 era., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Strictures and abdominal pain often complicate Crohn's disease (CD). The primary aim was to explore whether parameters obtained by preoperative contrast-enhanced (CE) ultrasonography (US) and dynamic CE MR Enterography (DCE-MRE) of strictures associates with biomechanical properties. CD patients undergoing elective small intestinal surgery were preoperatively examined with DCE-MRE and CEUS. The excised intestine was distended utilizing a pressure bag. Luminal and outer bowel wall cross-sectional areas were measured with US. The circumferential stricture stiffness (Young's modulus E ) was computed. Stiffness was associated with the initial slope of enhancement on DCE-MRE ( ρ = 0.63, p = 0.007), reflecting active disease, but lacked association with CEUS parameters. For structural imaging parameters, inflammation and stricture stiffness were associated with prestenotic dilatation on US (τ b = 0.43, p = 0.02) but not with MRE (τ b = 0.01, p = 1.0). Strictures identified by US were stiffer, 16.8 (14.0-20.1) kPa, than those graded as no or uncertain strictures, 12.6 (10.5-15.1) kPa, p = 0.02. MRE global score (activity) was associated with E ( ρ = 0.55, p = 0.018). Elastography did not correlate with circumferential stiffness. We conclude that increasing activity defined by the initial slope of enhancement on DCE-MRE and MRE global score were associated with stricture stiffness. Prestenotic dilatation on US could be a potential biomarker of CD small intestinal stricture stiffness.

An analysis of the impact of graded alcohol intake on glucose, insulin and free fatty acids levels in non-insulin-dependent diabetes mellitus, NIDDM, patients includes evaluation of blood glucose responses, insulin responses and quantitative evaluation of serum free fatty acids. The study involves the administration of non-alcohol beer in three doses, with of 0%, 2.7% and 5.4% of alcohol. Glycaemic regulation in NIDMM patients is unaffected by small percentages of alcoholic content. It is suggested that drastic changes in carbohydrate metabolism can occur due to increased amounts of ethanol intake over a period of time.

Objective: To compare the number of contacts to general practice across 11 types of abdominal cancer in the 12 months preceding a diagnosis., Design: Nationwide register study., Setting: Danish general practice., Subjects: Forty-seven thousand eight hundred and ninety-eight patients diagnosed with oesophageal, gastric, colon, rectal, liver, gall bladder/biliary tract, pancreatic, endometrial, ovarian, kidney or bladder cancer in 2014-2018., Main Outcome Measures: Monthly contact rates and incidence rate ratios (IRRs) of daytime face-to-face, email and telephone consultations in general practice across different abdominal cancers. The analyses were conducted for each sex and adjusted for age, comorbidity, marital status and education., Results: Compared to women with colon cancer, women with rectal cancer had the lowest number of contacts to general practice (IRR 12 months pre-diagnostic (IRR -12 )=0.86 (95% CI: 0.80-0.92); IRR 1 month pre-diagnostic (IRR -1 )=0.85 (95% CI: 0.81-0.89)), whereas women with liver (IRR -12 =1.23 (95% CI: 1.09-1.38); IRR -1 =1.11 (95% CI: 1.02-1.20)), pancreatic (IRR -12 =1.08 (95% CI: 1.01-1.16); IRR 1 =1.52 (95% CI: 1.45-1.58)) and kidney cancer (IRR -12 =1.14 (95% CI: 1.05-1.23); IRR -1 =1.18 (95% CI: 1.12-1.24)) had the highest number of contacts. Men showed similar patterns. From seven months pre-diagnostic, an increase in contacts to general practice was seen in bladder cancer patients, particularly women, compared to colon cancer., Conclusions: Using pre-diagnostic contact rates unveiled that liver, pancreatic, kidney and bladder cancers had a higher and more prolonged use of general practice. This may suggest missed opportunities of diagnosing cancer. Thus, pre-diagnostic contact rates may indicate symptoms and signs for cancer that need further research to ensure early cancer diagnosis.Key pointsThe majority of cancer patients attend their general practitioner (GP) before diagnosis; however, little is known about the use of general practice across different abdominal cancers.This study suggests that a potential exists to detect some abdominal cancers at an earlier point in time.The contact patterns in general practice seem to be shaped by the degree of diagnostic difficulty.GPs may need additional diagnostic opportunities to identify abdominal cancer in symptomatic patients.

Background: Abdominal cancers represent 30% of all diagnosed cancers. Nevertheless, it is unknown if the general practitioner's (GP's) initial cancer suspicion varies for different abdominal cancer types and how this is associated with referrals to standardized cancer patient pathways (CPPs)., Objectives: To explore initial cancer suspicion in GPs and to investigate how this was associated with GP referrals to CPPs and the duration of the primary care interval (PCI) in 10 different abdominal cancer types., Methods: We conducted a cohort study on 1104 incident abdominal cancer patients diagnosed in Denmark in 2016 using a combination of survey and register-based data. Poisson regression was used to estimate associations between GP cancer suspicion, CPP referral and PCI duration., Results: The GPs initially suspected cancer or other serious disease in 46-78% of cases, lowest in kidney cancer, and referred 35-65% to a CPP, lowest in oesophageal cancer. The GP's suspicion at the first presentation was strongly associated with referral to a CPP. The median (0-11 days) and 75th percentile (3-32 days) PCIs varied between the abdominal cancer types. The likelihood of a long PCI was more than 3-fold higher when the GP did not initially suspect cancer., Conclusion: In up to half of abdominal cancer patients, there is no initial suspicion of cancer or serious disease. CPPs were used in only one-third to two-thirds of patients, depending on cancer type. For kidney cancer, as well as several abdominal cancers, we need better diagnostic strategies to support GPs to enable effective and efficient referral., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Intestinal stenosis is a common complication of Crohn's Disease (CD). Stenosis is associated with alteration of bowel mechanical properties. This study aims to quantitate the mechanical properties of the intestinal stenosis and to explore associations between histology and mechanical remodeling at stenotic intestinal sites in CD patients., Methods: Intestinal segments from stenotic sites were studied in vitro from 19 CD patients. A luminal catheter with a bag was used to stepwise pressurize the intestinal segments from 0-100 cmH 2 O with 10 cmH 2 O increments. B-mode ultrasound images were obtained at the narrowest part of the stenosis at each pressure level and morphometric parameters were obtained from ultrasound images. The mechanical behavior of the stenotic tissue were characterized by using an isotropic three dimensional strain energy function in Demiray model form, the mechanical constants were obtained by fitting the model to the recorded intraluminal pressure and the inner radius of the stenotic segment of the small bowel. Grading scores were used for histological analysis of inflammation, fibrosis, muscular hypertrophy and adipocyte proliferation in the intestinal layers. The collagen area fraction in intestinal layers was also calculated. Associations between histological and the mechanical constants (stiffness) were analyzed., Results: Chronic inflammation was mainly located in mucosa whereas fibrosis was found in submucosa. The mechanical remodeling was performed with changed mechanical constants ranged between 0.35-13.68kPa. The mechanical properties changes were associated mainly with chronic inflammation, fibrosis and combination of inflammation and fibrosis (R>0.69, P<0.001). Furthermore, the mechanical properties correlated with the collagen fraction in submucosa and muscular layers (R>0.53, P<0.05)., Conclusions: We quantitated the intestinal stenosis stiffness. Associations were found between bowel mechanical remodeling and histological changes at the stenotic site in CD patients., Statement of Significance: Although intestinal ultrasonography, CT and MRI can be used to diagnose Crohn's Disease (CD)-associated bowel strictures, these techniques may not have sufficient accuracy and resolution to differentiate predominantly inflammatory strictures from predominantly fibrotic strictures. The present study aims to quantitate the mechanical remodeling of intestinal stenosis and to explore the associations between histological parameters and mechanical properties at the intestinal stenotic sites in CD patients. For the first time, we quantitatively demonstrated that the mechanical properties of the intestinal wall in CD stenosis are associated with the chronic inflammation, fibrosis and collagen fraction in the intestinal layers. The results of this study may facilitate design and development of artificial biomaterials for gastrointestinal organs. The potential clinical implication of this study is that the histological characteristics in patients with CD can be predicted clinically by means of inflammation and fibrosis assessment in conjunction with tissue stiffness measurement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: More than 11,500 abdominal cancers are yearly diagnosed in Denmark. Nevertheless, little is known about which investigations the patients undergo before a diagnosis of abdominal cancer. We aimed to investigate the frequency and timing of selected diagnostic investigations during the year preceding an abdominal cancer diagnosis., Methods: We conducted a nationwide registry-based cohort study of patients aged ≥ 18 years who were diagnosed with a first-time abdominal cancer in 2014-2018. We included the following cancer types: oesophageal, gastric, colon, rectal, liver, gall bladder/biliary tract, pancreatic, endometrial, ovarian, kidney, and bladder cancer. Investigations of interest were transvaginal ultrasound, abdominal ultrasound, colonoscopy, gastroscopy, endoscopic retrograde cholangiopancreatography, cystoscopy, hysteroscopy, abdominal computed tomography and abdominal magnetic resonance imaging. Generalised linear models were used to calculate incidence rate ratios to enable comparison of monthly rates of investigations., Results: All types of investigations were performed, with varying frequency, across the 11 abdominal cancer types in the year preceding the diagnosis. Increased use of investigations revealed that the timing of the onset differed for the different abdominal cancers, with increases seen 2-6 months before the diagnosis. Abdominal ultrasound, colonoscopy and computed tomography were the investigations with the earliest increase., Conclusion: In the year before a diagnosis of an abdominal cancer, some patients appear to undergo investigations typically used to detect another cancer type. This indicates that a window of opportunity exists to diagnose some abdominal cancers at an earlier time point. Future studies should explore an alternative clinical pathway to promote earlier diagnosis of abdominal cancers., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The aim was to examine anti-tumor necrosis factor α (anti-TNFα) therapy influence changes on Th17 and Th22 cells in patients with spondyloarthritis (SpA), and its correlation with changes in clinical and magnetic resonance imaging (MRI) activity and chronicity scores. The Th17 and Th22 cells were assessed at baseline, after 12 and 52 weeks of anti-TNFα therapy by flow cytometry (ClinicalTrials.gov NCT4682724). The percentages of both Th17 and Th22 cells were increased by 70% at baseline compared with healthy controls (both p < 0.01). During treatment, these two subsets increased further to be 170% (Th17) and 123% (Th22) above levels in healthy controls (both p < 0.01). The same subsets decrease their expression of IL-23R significantly during the observation period (p < 0.05). High levels of Th17 and Th22 cells at baseline were associated with the degree of chronic changes in the sacroiliac joints on MRI and a good clinical response to anti-TNFα treatment after one year. Plasma levels were not associated with clinical changes. Th17 cells, and Th22 subsets, increased during one year of anti-TNF-α therapy in SpA, regardless of their clinical improvement. This supports that both the Th17 and Th22 subsets could be involved in the progression in SpA., (© 2019 APMIS. Published by John Wiley & Sons Ltd.)

Objective: Intestinal inflammation is frequent in patients with spondyloarthritis (SpA). Here, we test the validity of faecal calprotectin as a marker of intestinal inflammation in SpA patients and evaluate the response of adalimumab in patients with and without intestinal lesions.Method: Patients were included on the basis of active SpA with a Bath Ankylosing Spondylitis Disease Activity Index ≥ 4. After a 4 week non-steroidal anti-inflammatory drug washout period, patients were divided into two groups based on faecal calprotectin level (> 100 mg/kg, n = 15, and < 50 mg/kg, n = 15). Adalimumab 40 mg every other week was initiated. Patients with calprotectin >100 mg/kg received an additional 40 mg of adalimumab at baseline. Patients were followed with clinical examination at weeks 12, 20, and 52; magnetic resonance imaging (MRI) at weeks 0, 20, and 52; and endoscopy at weeks 0 and 20.Results: The groups were similar with regard to clinical disease activity measures at baseline. Faecal calprotectin above 100 mg/kg accurately identified patients with intestinal inflammation. Twelve of the 15 patients with elevated calprotectin had bowel lesions, compared to only one patient in the control group. On MRI, the group with elevated calprotectin had more inflammation in the sacroiliac joints. Finally, the group with intestinal inflammation had a better clinical response to adalimumab, as evaluated by the Ankylosing Spondylitis Disease Activity Score.Conclusion: Elevated faecal calprotectin accurately identified SpA patients with bowel inflammation and more inflammation on MRI. Elevated faecal calprotectin at baseline may predict a better treatment response. [ABSTRACT FROM AUTHOR]