Interpretable inflammation landscape of circulating immune cells.

BackgroundRheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis are immune-mediated inflammatory diseases with similarities in pathophysiology, and all can be treated with similar biological agents. Previous studies have shown that there are gender differences with regard to disease characteristics in RA and IBD, with women generally having worse scores on pain and quality of life measurements. The relationship is less clear for psoriasis. Because treatment differences between men and women could explain the dissimilarities, we investigated gender differences in the disease characteristics before treatment initiation and in the biologic treatment prescribed.MethodsData on patients with RA or IBD were collected from two registries in which patients treated with biologic medication were enrolled. Basic demographic data and disease activity parameters were collected from a time point just before the initiation of the biologic treatment. For patients with psoriasis, the data were taken from the 2010 annual report of the Swedish Psoriasis Register for systemic treatment, which included also non-biologic treatment. For all three diseases, the prescribed treatment and disease characteristics were compared between men and women.ResultsIn total, 4493 adult patients were included in the study (1912 with RA, 131 with IBD, and 2450 with psoriasis). Most of the treated patients with RA were women, whereas most of the patients with IBD or psoriasis were men. There were no significant differences between men and women in the choice of biologics. At treatment start, significant gender differences were seen in the subjective disease measurements for both RA and psoriasis, with women having higher (that is, worse) scores than men. No differences in objective measurements were found for RA, but for psoriasis men had higher (that is, worse) scores for objective disease activity measures. A similar trend to RA was seen in IBD.ConclusionsWomen with RA or psoriasis scored significantly higher on subjective, but not on objective, disease activity measures than men, and the same trend was seen in IBD. This indicates that at the same level of treatment, the disease has a greater effect in women. These findings might suggest that in all three diseases, subjective measures are discounted to some extent in the therapeutic decision-making process, which could indicate undertreatment in female patients.

We compared the performance of a fluorescence lateral flow assay (ichroma™ IGRA-TB) with the QuantiFERON-TB Gold PLUS (QFT-PLUS) for the diagnosis of latent tuberculosis infection (LTBI) in patients with immune-mediated inflammatory diseases (IMID) prior to receiving biologics therapy. The comparability of the ichroma™ IGRA-TB assay with the QFT-PLUS assay for the diagnosis of LTBI was determined in prospectively enrolled patients with IMID prior to receiving biologics between August 2018 and October 2019. To determine the best cut-off value of the ichroma™ IGRA-TB, an ROC curve analysis was performed. Patients with IMID (n = 145) had inflammatory bowel disease (n = 83; 57.2%), rheumatoid arthritis (n = 44; 30.3%), or spondyloarthropathy (n = 18; 12.4%). The median age was 40.5 (interquartile range: 27.0-56.0), 72 (49.7%) were men, and 140 (96.6%) received BCG vaccination. With the manufacturer-recommended cut-off values, 11 (7.6%) and 20 (13.8%) patients showed positive results with the ichroma™ IGRA-TB and QFT-PLUS tests, respectively. The overall agreement between the two tests was 91.0% with a Cohen's kappa value of 0.535 (95% confidence interval: 0.317-0.754). ROC curve analysis of the QFT-PLUS results showed that a cut-off value of > 0.21 IU/mL would improve the performance of the ichroma™ IGRA-TB. Using the new cut-off value, the concordance rate was improved to 93.1% with a Cohen's kappa value of 0.668 (95% confidence interval: 0.478-0.858). The ichroma™ IGRA-TB could be used as a point-of-care test for LTBI screening in IMID patients before starting biologics, especially in resource-limited settings. Key Points • The ichroma™ IGRA-TB is an automated fluorescence lateral flow assay-based IGRA. • The test has advantages like short turn-around time, low-cost, and ease of use. • The ichroma™ IGRA-TB showed high agreement with the QuantiFERON-TB Gold In-Tube in patients with chronic immune-mediated inflammatory diseases before starting biologics.

TNF-α is produced in high concentrations in chronic inflammatory disease, resulting in excessive inflammation which eventually leads to organ damage. The advent of anti-TNF therapy in clinical practice 20 years ago represented a significant change in the management of immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis (RA), axial spondylarthritis (SpA), psoriasis, and inflammatory bowel disease (IBD). There are five anti-TNFs approved for use in IMIDs: infliximab, adalimumab, golimumab, etanercept, and certolizumab pegol. The structural and pharmacological differences between these agents mean that they can have differential efficacy across IMIDs, and therefore the indications for which they are approved vary. This mini-review aims to summarise the current understanding of anti-TNF efficacy in those IMIDs for which they are approved, focussing on data from meta-analyses of randomised clinical trials (RCTs), and real-world studies.

Letter from the Editor: Cost-effectiveness of tuberculosis screening in patients already on biologic therapy

Background:It is recommended that people with immune mediated inflammatory diseases (IMIDs) who take immunosuppressive medication receive at least 3 COVID-19 vaccinations in order to generate anti-SARSCoV2 antibody levels similar to...

Introduction: Immune-mediated inflammatory diseases (IMIDs) including ulcerative colitis, Crohn’s disease, psoriasis and rheumatoid arthritis are chronic conditions that affect millions of individuals worldwide. Various treatments have been prescribed for IMIDs, including topical agents, systemic corticosteroids, immunomodulators, and biologic agents. However, as is true for most medications that target chronic diseases, adherence to systemic therapies including biologics remains suboptimal. Methods: An adherence survey was used in Lebanon to evaluate physicians’ beliefs about adherence to medication in IMID and to evaluate if and how adherence was managed in their local practice. The survey was distributed to 100 randomly selected physicians from 3 different specialties (25 Rheumatologists, 37 Gastroenterologists, and 38 Dermatologists). Results were analyzed by 4 academic experts charged with developing an action plan to address practical and perceptual barriers to improve and integrate adherence into treatment goals to maximize outcomes in IMID, and elevate local standards of care. Results: Eighty-two physicians participated in this study and completed the questionnaire. Most defined adherence as compliance with prescribed treatment. Although the majority of surveyed physicians (74%) did not systematically measure adherence in their practice, 54% identified adherence as a treatment goal of equal or greater importance to therapeutic endpoints. Doctor-patient relationship (38%), fear of treatment side effects (35%), adjustment disorder (34%), and disease chronicity (32%) were thought to commonly affect adherence. Lack of time and specialized nursing support were reported as important barriers to measuring adherence. The expert panel identified 4 key areas for action: 360° education (patient-nurse-physician), patient-physician communication, patient perception and concerns about the disease and its treatment, and market access/cost. An action plan was developed centered on education and awareness, enhanced benefit-risk communication, development of adherence assessment tools, and promotion of patient support programs. Conclusion: Non-adherence to medication is a commonly underestimated problem with important consequences. Healthcare professionals are not always aware when patients fail to adhere to prescribed treatment, mainly because they lack time, support and guidance tools to assess adherence. A customized target-based strategy to address the root causes of non-adherence is essential in the management of IBD and other chronic IMIDs. This research was supported by an industry grant from Study sponsored by AbbVie.

The concentrations of the acute-phase proteins, serum amyloid-A (SAA) and haptoglobin (Hp), were determined in the plasma of healthy cows (n = 25) and cows with spontaneous acute (n = 6), subacute (n = 37), or chronic (n = 7) inflammatory diseases. The plasma concentration of SAA alone, Hp alone, and the Hp/SAA ratio, differed significantly (p < 0.001) between healthy animals and animals with inflammatory diseases. Plasma Hp concentrations in the group of cows with acute inflammatory diseases were significantly (p < 0.01) different from those in the group with chronic inflammatory diseases. Moreover, the Hp/SAA ratio in chronic inflammatory diseases was significantly different from this ratio in acute (p < 0.01) and subacute (p < 0.05) inflammatory diseases. It is therefore concluded that the plasma concentrations of SAA and Hp and the Hp/SAA ratio are useful parameters to distinguish healthy animals from animals with inflammation and can be helpful in distinguishing between acute and chronic of inflammatory diseases.

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses. This observational cohort study collected plasma and PBMCs from healthy control subjects and untreated or treated patients with IMIDs prevaccination and after one to four doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). SARS-CoV-2-specific Ab levels, neutralization, and T cell cytokine release were measured against wild-type and Omicron BA.1 and BA.5 variants of concern. Third vaccine doses substantially restored and prolonged Ab and T cell responses in patients with IMIDs and broadened responses against variants of concern. Fourth-dose effects were subtle but also prolonged Ab responses. However, patients with IMIDs treated with anti-TNF, especially patients with inflammatory bowel disease, exhibited lower Ab responses even after the fourth dose. Although T cell IFN-γ responses were maximal after one dose, IL-2 and IL-4 production increased with successive doses, and early production of these cytokines was predictive of neutralization responses at 3-4 mo postvaccination. Our study demonstrates that third and fourth doses of the SARS-CoV-2 mRNA vaccines sustain and broaden immune responses to SARS-CoV-2, supporting the recommendation for three- and four-dose vaccination regimens in patients with IMIDs.

Although mood disorders have been well characterized by immunemediated inflammatory diseases, physical function and satisfaction with social roles have not yet been defined as independent domains. The study aims to assess satisfaction with social roles and physical function alterations in a population with immune-mediated inflammatory diseases and identify associated characteristics. Physical function and social role satisfaction were evaluated through the Patientreported Outcomes Measurement System. Besides comparison between groups, univariate and multivariable logistic regression analyses were performed to identify independent predictors. Two hundred sixty-five patients with immune-mediated inflammatory diseases and 206 controls were recruited. Compared to controls, patients with inflammatory bowel diseases had impaired physical function (p<0.001), while patients with inflammatory arthritis reported impairment in both domains (p<0.001, each). In the univariate logistic regression, gender, high school educational level, physical activity, and occupation were positively associated with physical function and social role satisfaction (p<0.001; p=0.001; p<0.001; p=0.001 and p<0.001; p=0.012; p=0.008; p=0.004, respectively). Active disease and steroids were inversely associated with physical function and social roles satisfaction (p=0.033; p=0.022 and p=0.002; p=0.038, respectively). Further associations were found between age and physical function (p=0.002) and biological treatment and ESR with social roles satisfaction (p<0.001; p=0.043; respectively). In the multivariable regression, gender was found to be associated with physical function (p<0.001) and social roles satisfaction (p=0.003). Negatively associated factors were biological treatment for satisfaction with social roles (p<0.001) and steroids for physical function (p=0.021), and social roles satisfaction (p=0.018). Immune-mediated inflammatory diseases determine alterations in physical function and social life satisfaction. Gender and treatment are independently associated factors. Patientreported outcomes should be considered in clinical management to define patients' real needs.

The environmental and occupational risk we confront from agricultural chemicals increases as their presence in natural habitats rises to hazardous levels, building a major part of the exposome. This is of particular concern in low- and middle-income countries, such as Brazil, known as a leading producer of agricultural commodities and consumer of pesticides. As long as public policies continue to encourage the indiscriminate use of pesticides and governments continue to support this strategy instead of endorsing sustainable agricultural alternatives, the environmental burden that damages epithelial barriers will continue to grow. Chronic exposure to environmental contaminants in early life can affect crucial barrier tissue, such as skin epithelium, airways, and intestine, causing increased permeability, leaking, dysbiosis, and inflammation, with serious implications for metabolism and homeostasis. This vicious cycle of exposure to environmental factors and the consequent damage to the epithelial barrier has been associated with an increase in immune-mediated chronic inflammatory diseases. Understanding how the harmful effects of pesticides on the epithelial barrier impact cellular interactions mediated by endogenous sensors that coordinate a successful immune system represents a crucial challenge. In line with the epithelial barrier hypothesis, this narrative review reports the available evidence on the effects of pesticides on epithelial barrier integrity, dysbiosis, AhR signaling, and the consequent development of immune-mediated inflammatory diseases.

We aimed to examine rates of breast and cervical cancer screening in women with immune-mediated inflammatory diseases (IMID), including inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) versus a matched cohort with IMID; and examine the association of psychiatric comorbidity with screening in these populations. We conducted a retrospective cohort study in Manitoba, Canada using administrative data. We identified women with IBD, MS and RA, and controls without these IMID matched on age and region. Annually, we identified individuals with any active mood/anxiety disorder. Using physician claims, we determined the proportion of each cohort who had cervical cancer screening within three-year intervals, and mammography screening within two-year intervals. We modeled the difference in the proportion of the IMID and matched cohorts who underwent mammography; and pap tests using log-binomial regression with generalized estimating equations, adjusting for sociodemographics, comorbidity and immune therapy use. We tested for additive interactions between cohort and mood/anxiety disorder status. During 2006–2016, we identified 17,230 women with IMID (4,623 with IBD, 3,399 with MS, and 9,458 with RA) and 85,349 matched controls. Having an IMID was associated with lower (-1%) use of mammography; however, this reflected a mixture of more mammography in the IBD cohort (+2.9%) and less mammography in the MS (-4.8 to -5.2%) and RA (-1.5%) cohorts. Within the IBD, MS and RA cohorts, having an active mood/anxiety disorder was associated with more mammography use than having an inactive mood/anxiety disorder. The MS and RA cohorts were less likely to undergo Pap testing than their matched cohorts. In the absence of an active mood/anxiety disorder, the IBD cohort was more likely to undergo Pap testing than its matched cohort; the opposite was true when an active mood/anxiety disorder was present. Among women with an IMID, mood/anxiety disorder influence participation in cancer screening.

BackgroundMyocardial fibrosis is an important adverse prognostic marker, however; determinants of myocardial fibrosis in immune-mediated inflammatory diseases (IMIDs) remain poorly defined. We aimed to identify determinants of myocardial fibrosis in patients with IMIDs, as measured by cardiovascular magnetic resonance (CMR) extracellular volume (ECV).MethodsCross-sectional study of 116 patients with IMIDs undergoing clinical CMR at Manchester University NHS Foundation Trust. IMIDs included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (SSc), ankylosing spondylitis, psoriatic arthritis and vasculitis. CMR included pre- and post-contrast T1 mapping to measure myocardial ECV, with same day blood sampling. Determinants of ECV were investigated with univariable and multivariable linear regression.ResultsECV varied significantly according to IMID diagnosis (ANOVA F statistic 2.80, P = 0.015); ECV was higher in patients with SSc compared to other IMIDs. Major determinants of ECV as a continuous variable were SSc, smoking and body mass index (BMI); regression coefficients 3.33 (95% confidence interval 0.82–5.84), 3.08 (0.73–5.43), and − 0.19 (-0.29 – -0.09) respectively, P < 0.01 (SSc, smoking and lower BMI were associated with increased ECV). Approximately a quarter of the variability in ECV could be explained by these predictors (optimism adjusted R2 0.265).ConclusionSSc is associated with a higher burden of myocardial fibrosis compared to other IMIDs. In patients with IMIDs, independent determinants of myocardial fibrosis were presence of SSc, smoking and BMI. Importantly, participants underwent CMR for clinical indications and may not be representative of IMID populations in the community.

Sarcopenia and immune-mediated inflammatory diseases: Evaluating causality and exploring therapeutic targets for sarcopenia through Mendelian randomization.

Background/Aims Listeria monocytogenes is a gram-positive bacterium found ubiquitously in the environment. Human infection is relatively rare and usually occurs after consumption of contaminated food. L. monocytogenes can cause an uncomplicated gastroenteritis in the immunocompetent. Vulnerable individuals are at risk of invasive disease. These include the elderly, pregnant women, neonates and people with impaired immunity, including those treated with biologics and targeted therapies for immune-mediated inflammatory diseases (IMIDs). Invasive listeriosis typically causes bacteraemia, meningoencephalitis and maternal-neonatal infection. Other reviews have described an association between TNF-alpha inhibitors and invasive listeriosis, however the impact of newer biologics and the JAK-inhibitors has not been described. Methods The literature was systemically reviewed to assess the incidence of invasive listeriosis in patients with IMIDs treated with biologics or targeted therapies using Ovid Medline, EMBASE and the Cochrane Database of Systematic Reviews. Papers including patients over 16 years of age with rheumatoid arthritis (RA), ankylosing spondylitis (AS), axial spondyloarthritis, psoriatic arthritis, psoriasis, inflammatory bowel disease (IBD), (ulcerative colitis or Crohn’s disease), managed with biologics or targeted therapies were included. Abstracts, case reports, case series, cohort studies, registry studies, randomised controlled trials and meta-analyses were included. Reports not published in English or not detailing the name of the biologic or targeted therapy used were excluded. The primary outcome was incidence of invasive listeriosis defined as isolation of L. monocytogenes from a normally sterile site. Results Thirty-eight case reports, three disease-specific registry analyses, two randomised controlled trials and one meta-analysis were included in the final results. Together these studies reported 75 cases of invasive listeriosis in patients with IMIDs on biologics and targeted therapies. Seventy cases were described in patients treated with TNF-alpha inhibitors (49 with infliximab, nine with adalimumab, one with certolizumab pegol, one with golimumab and ten with etanercept). Two cases were described in patients treated with IL-12/IL-23 inhibitors (one with ustekinumab and one with guselkumab), one case was described in a patient treated with a gut-selective integrin antagonist (vedolizumab), one case in a patient treated with tocilizumab (an IL-6 inhibitor) and one case in a patient treated with a JAK-inhibitor (tofacitinib). Thirty-four patients had RA, 31 had IBD, five had psoriatic arthritis, two had ankylosing spondylitis, one had both psoriasis and psoriatic arthritis, one had psoriasis and another an unknown IMID. The reporting of listeriosis cases with TNF-alpha inhibitors has remained fairly steady over time so this association is not purely an early reporting phenomenon. Conclusion Cases of invasive listeriosis have been reported across a range of different IMIDs, most often in patients with RA and IBD. Invasive listeriosis is not unique to patients treated with TNF-alpha inhibitors. The association between invasive listeriosis and other targeted therapies (e.g. IL-23 inhibition) needs further study. Disclosure V. Allen: None. E. Alveyn: None. J. Galloway: Honoraria; AbbVie, Celgene, Chugai, Gilead, Janssen, Eli Lilly, Pfizer, Roche and UCB.

The effect of phototherapy on systemic inflammatory process in patients with plaque psoriasis