Citations

ABSTRACT HLA‐B*15:591 is characterised by a single nucleotide substitution in codon 219 in exon 4.

Objectives Rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are linked to disease activity, severity and cardiovascular risk in rheumatoid arthritis (RA). Since RA-related inflammation associates with cardiovascular disease, we investigated whether RF and ACPA status influence the relationship between RA activity and event risk. Methods We assessed 3952 cardiovascular disease-free patients with prevalent RA registered in an international observational consortium between 1985 and 2012. Main outcome was a first major adverse cardiovascular event (MACE) including myocardial infarction, stroke and cardiovascular death. Follow-up accrued from enrolment until first MACE or censoring. Multivariable Cox models stratified by centre risk evaluated disease activity, RF, ACPA and their interactions. Results We recorded 184 first MACE events over 22 981 patient-years. Disease activity associated with MACE (HR 1.18 (95% CI 1.03 to 1.35)), whereas RF (HR 1.26 (0.82 to 1.94)) and ACPA (HR 1.25 (0.85 to 1.83)) did not reach statistical significance, though CIs were wide and a clinically meaningful association cannot be excluded. A three-way interaction between disease activity, RF and ACPA on MACE (p for interaction=0.044) was observed. RA activity associated with MACE in seronegative and double seropositive (p≤0.047), but not single RF-positive or ACPA-positive patients. Among RF-negative participants, RA activity was linked to MACE in ACPA-negative but not positive ones (p for interaction=0.003). Among ACPA-positive patients, disease activity was linked to MACE in RF-positive but not RF-negative ones (p for interaction=0.040). Conclusions Disease activity may better discriminate inflammation-driven cardiovascular risk in seronegative and double seropositive than single RF-positive or ACPA-positive patients. Risk protection through lowering disease activity may be serostatus dependent.

Abstract Introduction Despite regulatory mandates for advanced therapy (AT) washout periods of up to 5 drug half-lives before enrolling patients in inflammatory bowel disease (IBD) trials, the evidence base for these requirements is largely empirical, and whether shorter intervals independently increase the risk of serious infections in real-world practice remains unknown. Methods Using the OptumLabs Data Warehouse, we identified adult patients with IBD who initiated a new AT (tumor necrosis factor antagonists, vedolizumab, interleukin (IL)-12/23 or IL-23 antagonists, or Janus kinase inhibitors) between 2018 and 2023 using a class-specific new-user design. We examined whether exposure to AT within the preceding 12 months (vs no exposure to AT within that window) and timing of discontinuation (≤1 month, 1-<3 months, or 3-12 months) were associated with risk of serious infections using multivariable Cox proportional hazards regression. Results Among 21 564 AT initiators (47 ± 18 years; 52% female; 57% Crohn’s disease), 7490 (34.7%) had AT exposure within the preceding 12 months. Over a mean follow-up of 1.6 ± 0.9 y, 1955 (9.1%) experienced a serious infection. Prior AT exposure was associated with higher infection risk (hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.07-1.33), consistent in inverse probability of treatment-weighted analyses (HR, 1.20 [1.06-1.37]). Among patients with prior exposure, timing of discontinuation was not associated with infection risk (HR, 1.17 [0.95-1.43] for ≤1 month vs 3-12 months; HR, 1.01 [0.83-1.22] for 1-<3 months), with no dose–response relationship on continuous modeling. Discussion AT exposure within the preceding 12 months is associated with modestly higher risk of serious infection after initiating a new AT in IBD, but timing of discontinuation does not independently influence this risk.

ABSTRACT HLA‐C*01:155 is characterised by a single nucleotide substitution in codon 225 in exon 4.

ABSTRACT The novel HLA‐A*26:268 allele is characterised by a single nucleotide substitution in exon 7.

ABSTRACT The HLA‐DQA1*01:169 allele is characterised by a single nucleotide substitution in codon 175 in exon 3.

INTRODUCTION: Computed tomography enterography (CTE) is a noninvasive cross-sectional imaging modality routinely used for diagnosis of Crohn's disease (CD) strictures. However, CTE is limited in individually defining the severity of inflammation, fibrosis, or smooth muscle hyperplasia/hypertrophy (SMH) within such strictures. We developed and internally validated a radiomics-based machine learning model for separately characterizing the degree of histopathological inflammation, fibrosis, and SMH in CD strictures and compared it with centrally read visual radiologist scoring of CTE. METHODS: This single-center, cross-sectional study included 100 patients with CD (n = 66 for discovery; n = 34 for validation) with terminal ileal strictures confirmed on diagnostic CTE within 15 weeks of intestinal resection. Histopathological specimens were scored for inflammation, fibrosis, and SMH and spatially linked with corresponding pre-surgical CTE sequences. Annotated stricture regions on CTE were scored visually by radiologists as well as underwent three-dimensional radiomics-based machine-learning analysis; both evaluated against histopathology scoring. RESULTS: Three distinct sets of radiomic features capturing textural heterogeneity within strictures were separately linked with severe inflammation, fibrosis, and SMH across both discovery (accuracy = 0.74, 0.71, 0.71, respectively) and validation (accuracy = 0.74, 0.68, 0.68, respectively) cohorts. Radiologist visual scoring was limited, with accuracy of 0.51 for identifying severe inflammation, 0.48 for severe fibrosis, and 0.58 for severe SMH. Augmenting radiologist scoring with radiomic features yielded improved performance in identifying severe inflammation, fibrosis, or SMH compared to radiologist scoring alone. DISCUSSION: Radiomic features of CD strictures on CTE can identify severe histopathological fibrosis, inflammation, and smooth muscle hyperplasia and perform better than radiologist visual scoring in stricture characterization.