Weisman, Michael H.

ABSTRACT Background Polypharmacy is common in autoimmune rheumatic diseases (ARDs) and increases adverse drug events (ADEs), but comparative evidence across diseases is limited. We aimed to quantify ADE burden and identify medications associated with ADE risk across six ARDs, and to examine shared and disease-specific patterns across diseases. Methods We conducted a retrospective cohort study at a tertiary medical center (2010–2024). Adults with ankylosing spondylitis (AS), psoriatic arthritis (PsA), rheumatoid arthritis (RA), Sjögren’s disease (SjD), systemic lupus erythematosus (SLE), or systemic sclerosis (SSc) were identified using diagnostic codes. ADEs were ascertained using validated case definitions. Medications were mapped to Anatomical Therapeutic Chemical classes; active exposure was defined within 30 days before the index date. Polypharmacy was defined as ≥5 concurrent medications (minor 5–10; major >10). Within each ARD, nested case–control analyses matched on encounter type (1:4) were performed, and adjusted odds ratios (aORs) were estimated using conditional logistic regression. Findings Among 10,578 patients, 3,154 (29.8%) experienced at least one ADE. ADE burden varied across diseases, with the highest prevalence observed in SSc (35.9%). Polypharmacy was common (57.3% minor, 39.4% major) and medication burden was consistently higher in ADE cases across encounter types (eg, SLE outpatient median 12 vs 6; inpatient 20 vs 10; emergency 17 vs 8). Across ARDs, the strongest associations with ADEs were observed for supportive and symptom-directed therapies (acid suppressors, pain adjuncts, and sedative-hypnotic/psychotropic medications), whereas conventional disease-modifying antirheumatic drugs (DMARDs) showed weaker associations. Disease-specific signatures included gastrointestinal agents in SSc (metoclopramide aOR 12.32), antibiotics and respiratory agents in AS (ciprofloxacin aOR 13.71, fluticasone aOR 8.88). Interpretation ADEs affect nearly one-third of ARD patients and increase with medication burden. Risk concentrates in supportive and symptom-directed therapies rather than DMARDs, with both shared and disease-specific patterns. Optimizing prescribing, particularly for pain management and corticosteroid use, can reduce medication-related harm.

INTRODUCTION: Spondyloarthritis (SpA), the most common extraintestinal manifestation of inflammatory bowel disease (IBD), is reported in up to 39% of patients with IBD. Despite this high prevalence, risk factors of developing SpA in patients with IBD are not well described. In this study, we aimed to determine the factors associated with SpA symptoms and their prevalence in an IBD cohort. METHODS: Two validated screening questionnaires for the detection of SpA in IBD (DETAIL = DETection of Arthritis in Inflammatory boweL diseases, IBIS-Q = IBD Identification of Spondyloarthritis Questionnaire) were administered to patients with IBD without a prior diagnosis of SpA in 6 US academic medical centers. Demographic data, IBD characteristics, and medication history were recorded. RESULTS: Screening questionnaires were completed by 588 patients (220 ulcerative colitis, 349 Crohn's disease, and 19 IBD-unclassified), with a median age of 40 years (interquartile range 30–53) and median disease duration of 12 years (interquartile range 6–22). The number of positive screens was 130 (22%) for DETAIL, 196 (33%) for IBIS-Q, and 204 (35%) for either DETAIL or IBIS-Q. Age, female sex, history of smoking, prior bowel surgery, and history of any biologic or targeted small molecule exposure were associated with a positive screen on univariate analysis. After multivariate analysis, female sex (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.41–2.93), older age (OR 1.02, 95% CI 1.01–1.04), history of smoking (OR 1.67, 95% CI 1.04–2.69), and history of any biologic or targeted small molecule exposure (OR 2.27, 95% CI 1.34–3.84) were independently associated with positive screens. Higher number of biologic exposures was associated with higher risk of positive screens, with the highest risk seen with 3 or more exposures (OR 3.25, 95% CI 1.75–6.03). DISCUSSION: A substantial number of patients with IBD screen positive for SpA symptoms, indicating a potentially high burden of undiagnosed illness. Factors associated with SpA symptoms include older age, female sex, and more severe disease (based on increased number of advanced therapies or prior surgery), whereas IBD phenotype does not independently increase the risk of a positive SpA screen. Further studies are needed to confirm these findings and better characterize SpA in IBD.

Abstract Background Inflammatory bowel disease (IBD)–associated peripheral spondyloarthritis (pSpA) decreases quality of life and remains poorly understood. Given the prevalence of this condition and its negative impact, it is surprising that evidence-based disease definitions and diagnostic strategies are lacking. This systematic review summarizes available data to facilitate development and validation of diagnostics, patient-reported outcomes, and imaging indices specific to this condition. Methods A literature search was conducted. Consensus or classification criteria, case series, cross-sectional studies, cohort studies, and randomized controlled trials related to diagnosis were included. Results A total of 44 studies reporting data on approximately 1500 patients with pSpA were eligible for analysis. Data quality across studies was only graded as fair to good. Due to large heterogeneity, meta-analysis was not possible. The majority of studies incorporated patient-reported outcomes and a physical examination. A total of 13 studies proposed or validated screening tools, consensus, classification, or consensus criteria. A total of 28 studies assessed the role of laboratory tests, none of which were considered sufficiently accurate for use in diagnosis. A total of 17 studies assessed the role of imaging, with the available literature insufficient to fully endorse any imaging modality as a robust diagnostic tool. Conclusions This review highlights existing inconsistency and lack of a clear diagnostic approach for IBD-associated pSpA. Given the absence of an evidence-based approach, a combination of existing criteria and physician assessment should be utilized. To address this issue comprehensively, our future efforts will be directed toward pursuit of a multidisciplinary approach aimed at standardizing evaluation and diagnosis of IBD-associated pSpA.

SummaryBackground and aimsExtra‐intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited.MethodsAs a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty‐four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds.ResultsFor use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence.ConclusionsConsensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician‐reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs.

ObjectiveSystemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE.MethodsPreviously identified blood relatives of patients with SLE, who had <4 American College of Rheumatology (ACR) classification criteria for SLE at baseline, were enrolled in this follow‐up study (n = 409 unaffected relatives). Participants provided detailed family, demographic, and clinical information, including the SLE‐specific portion of the Connective Tissue Disease Screening Questionnaire (SLE‐CSQ). Serum and plasma samples were tested for the presence of lupus‐associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEEs) were applied to identify factors predictive of disease transition.ResultsOf the 409 unaffected relatives of SLE patients, 45 (11%) had transitioned to classified SLE at follow‐up (mean time to follow‐up 6.4 years). Relatives who transitioned to SLE displayed more lupus‐associated autoantibody specificities and higher SLE‐CSQ scores (P < 0.0001) at baseline than did relatives who did not transition. Importantly, those who had developed SLE during the follow‐up period also had elevated baseline plasma levels of inflammatory mediators, including B lymphocyte stimulator, stem cell factor (SCF), and interferon‐associated chemokines (P ≤ 0.02), with concurrent decreases in the levels of regulatory mediators, transforming growth factor β (TGFβ), and interleukin‐10 (P ≤ 0.03). GEE analyses revealed that baseline SLE‐CSQ scores or ACR scores (number of ACR criteria satisfied) and plasma levels of SCF and TGFβ, but not autoantibodies, were significant and independent predictors of SLE transition (P ≤ 0.03).ConclusionPreclinical alterations in levels of soluble mediators may predict transition to classified disease in relatives of SLE patients. Thus, immune perturbations precede SLE classification and can help identify high‐risk relatives for rheumatology referral and potential enrollment in prevention trials.