Duration of Postvaccination Neutralizing Antibodies to SARS-CoV-2 and Medication Effects: Results from the Safety and Immunogenicity of COVID-19 Vaccination in Systemic Immune-Mediated Inflammatory Diseases Cohort Study.

OBJECTIVE: In the face of the ongoing circulation of SARS-CoV-2, the durability of neutralization post-COVID-19 vaccination in immune-mediated inflammatory disease (IMID) is a key issue, as are the effects of medications. METHODS: Adults (n = 112) with inflammatory bowel disease, psoriasis/psoriatic arthritis, rheumatoid arthritis, spondylarthritis, and systemic lupus were recruited from participating Canadian medical centers from 2021 to 2023. We focused on log-transformed neutralization (lentivirus methods) as a continuous outcome, with separate models for wild-type and Omicron strains BA.1 and BA.5. RESULTS: Compared with 30 to 120 days postvaccination, subsequent periods were associated with greater neutralization in unadjusted models for wild-type, BA.1, and BA.5 strains and against the BA.1 strain in adjusted models. Rituximab was associated with lower neutralization for the BA.1 strain in adjusted models, with a similar trend for BA.5. In methotrexate users, there were trends for less neutralization of BA.1 and BA.5 in all unadjusted models, whereas in adjusted models, there was significantly lower neutralization only for the wild type. Three or more doses and Omicron-specific vaccines were both independently associated with better neutralization ability for all three strains. A COVID-19 infection within six months before sampling was associated with higher neutralization of wild type and BA.1 in adjusted analyses. Anti-tumor necrosis factor agents were associated with lower neutralization ability for BA.5 in adjusted analyses. CONCLUSION: Neutralization responses in immunosuppressed individuals with IMID were durable over time and were augmented by more than three doses and Omicron-specific vaccines. Less neutralization was seen with certain medications. Our work clarifies the joint effects of vaccine history, infection, and medications on COVID-19 immunity.

When Should I Get My Next COVID-19 Vaccine? Data From the Surveillance of Responses to COVID-19 Vaccines in Systemic Immune-Mediated Inflammatory Diseases (SUCCEED) Study.

OBJECTIVE: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors. METHODS: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG. RESULTS: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days. CONCLUSION: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection.

Utility of Baseline Transcriptomic Analysis of Rheumatoid Arthritis Synovium as an Indicator for Long-Term Clinical Outcomes.

Objective: Rheumatoid arthritis is a chronic inflammatory autoimmune disease that can lead to synovial damage, persistent joint pain, and functional disability. Our objective was to evaluate baseline synovial transcriptome from early inflammatory arthritis patients (EIA) and identify pretreatment biomarkers that could potentially provide insights into long-term functional outcomes of rheumatoid arthritis (RA). Methods: Synovial biopsies from clinically inflamed knee joints were procured from either 17 EIA patients before initiation of disease modifying anti-rheumatic drug (DMARD) therapy (DMARD-naïve EIA) using the minimally invasive closed needle biopsy technique or advanced RA patients undergoing arthroplasty. Affymetrix Human Genome U133 Plus 2 microarray platform was used to profile the synovial transcriptome. The cohort was followed clinically for a median of 12.3 years, and patient data was collected at each visit. Short-term and long-term clinical outcomes were determined by assessing RA-associated clinical parameters Statistical adjustments were made to account for asynchronous clinical visits and duration of follow up. Results: Based on the transcriptomic analysis, we identified 5 differentially expressed genes (DEGs), including matrix metalloproteinase (MMP)-1 (fibroblast collagenase) and MMP-3 (stromelysin-1) in DMARD-naïve EIA patients, relative to advanced RA patients (q < 0.05). Dichotomous expression of MMP-1 and MMP-3 mRNA and protein was confirmed by qPCR and immunohistochemistry respectively, based on which DMARD-naïve EIA subjects were classified as MMP-high or MMP-low. Hierarchical clustering of transcriptomic data identified 947 DEGs between MMP-high and MMP-low cohorts. Co-expression and IPA analysis of DEGs in the MMP-high cohort showed an enrichment of genes that participated in metabolic or biochemical functions and intracellular immune signaling were regulated through NF-κB and ß-catenin complexes and correlated with markers of systemic inflammation. Analysis of short-term clinical outcomes in MMP-high cohort showed a significant reduction in the DAS-CRP scores relative to baseline (P <0.001), whereas area under the curve analyses of modified HAQ (mHAQ) scores correlated negatively with baseline MMP-1 (R = -0.59, P = 0.03). Further, longitudinal mHAQ scores, number of swollen joints, number of DMARDs and median follow-up duration appeared to be higher in MMP-low cohort. Conclusion: Overall, our results indicate that the gene expression profiling of synovial biopsies obtained at the DMARD-naive stage in patients with EIA categorizes them into subsets with varying degrees of inflammation and can predict the future of long-term clinical outcome.

Predictors of Influenza Vaccination in Early Rheumatoid Arthritis 2017-2021: Results From the Canadian Early Arthritis Cohort.

OBJECTIVE: Adults with rheumatoid arthritis (RA) are at a higher risk for infections, including influenza and related complications. We identified influenza vaccination coverage in adults newly diagnosed with RA and examined sociodemographic RA characteristics and attitudes associated with vaccination. METHODS: We used data from patients enrolled in the Canadian Early Arthritis Cohort between September 2017 and February 2021. At enrollment, participants reported their vaccination status in the previous year and completed the Beliefs About Medicines Questionnaire (BMQ). Clinical data were obtained from medical records. Logistic regression was used to identify predictors of vaccination in the year after RA diagnosis. RESULTS: The baseline analytic sample of 431 patients were mostly White (80%) women (67%) with a mean age of 56 (SD 14) years. Prediagnosis, influenza vaccine coverage was 38%, increasing to 46% post diagnosis in the longitudinal sample (n = 229). Participants with previous influenza vaccination (odds ratio [OR] 15.33; 95% confidence interval [CI] 6.37-36.90), on biologics or JAKs (OR 5.42; 95% CI 1.72-17.03), and with a higher change in BMQ Necessity-Concerns Differential scores (OR 1.08; 95% CI 1.02-1.15) had greater odds, whereas women (OR 0.32; 95% CI 0.14-0.71), participants with a non-White racial background (OR 0.13; 95% CI 0.04-0.51), and participants currently smoking (OR 0.09; 95% CI 0.02-0.37) had lower odds of influenza vaccine coverage. CONCLUSION: Influenza vaccination coverage in patients with early RA remains below national targets in adults living with a chronic condition. Discussing vaccine history and medication attitudes at initial clinic visits with new patients with RA may enhance vaccine acceptance and uptake.

COVID-19 Vaccination Uptake Among Individuals With Immune-mediated Inflammatory Diseases in Ontario, Canada, Between December 2020 and October 2021: A Population-based Analysis.

OBJECTIVE: We assessed coronavirus disease 2019 (COVID-19) vaccine uptake among individuals with immune-mediated inflammatory diseases (IMIDs) and the Ontario general population. METHODS: We studied all residents aged ≥ 16 years who were alive and enrolled in the Ontario Health Insurance Plan as of December 14, 2020, when vaccination commenced (n = 12,435,914). Individuals with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), psoriasis (PsO), and inflammatory bowel disease (IBD) were identified using established disease-specific case definitions applied to health administrative data. Vaccination status was extracted from the provincial COVaxON registry. Weekly cumulative proportions of first and second doses up until October 3, 2021, were expressed as the vaccinated percentage of each disease group, compared to the general Ontario population, and stratified by age. RESULTS: By October 3, 2021, the cumulative percentage with at least 1 dose was 82.1% for the general population, 88.9% for those with RA, 87.4% for AS, 90.6% for PsA, 87.3% for PsO, and 87.0% for IBD. There was also a higher total cumulative percentage with 2 doses among IMIDs (83.8-88.2%) vs the general population (77.9%). The difference was also evident when stratifying by age. Individuals with IMIDs in the youngest age group initially had earlier uptake than the general population but remain the lowest age group with 2 doses (70.6% in the general population vs. 73.7-79.2% across IMID groups). CONCLUSION: While implementation of COVID-19 vaccination programs has differed globally, these Canadian estimates are the first to reassuringly show higher COVID-19 vaccine uptake among individuals with IMIDs.

Characterization and use of the ECV304 autoantigenic citrullinome to understand anti-citrullinated protein/peptide autoantibodies in rheumatoid arthritis.

BACKGROUND: Anti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). In vivo, ACPAs target peptidyl-citrulline epitopes (cit-) in a variety of proteins (cit-prot-ACPAs) and derived peptides (cit-pept-ACPAs) generated via the peptidylarginine deiminase (PAD) isoenzymes. We aimed to identify a cell line with self-citrullination capacity, to describe its autoantigenic citrullinome, and to test it as a source of autocitrullinated proteins and peptides. METHODS: Human cell lines were screened for cit-proteins by Western blot. PAD isoenzymes were identified by RT-PCR. Autocitrullination of ECV304 was optimized, and the ECV304 autocitrullinomes immunoprecipitated by sera from three RA patients were characterized by mass spectrometry. Cit-pept-ACPAs were detected using anti-CCP2 ELISA and cit-prot-ACPAs, by an auto-cit-prot-ECV304 ELISA. Sera from 177 RA patients, 59 non-RA rheumatic disease patients and 25 non-disease controls were tested. RESULTS: Of the seven cell lines studied, only ECV304 simultaneously overexpressed PAD2 and PAD3 and its extracts reproducibly autocitrullinated self and non-self-proteins. Proteomic analysis of the cit-ECV304 products immunoprecipitated by RA sera, identified novel cit-targets: calreticulin, profilin 1, vinculin, new 14-3-3 protein family members, chaperones, and mitochondrial enzymes. The auto-cit-prot-ECV304 ELISA had a sensitivity of 50% and a specificity of 95% for RA diagnosis. CONCLUSIONS: ECV304 cells overexpress two of the PAD isoenzymes capable of citrullinating self-proteins. These autocitrullinated cells constitute a basic and clinical research tool that enable the detection of cit-prot-ACPAs with high diagnostic specificity and allow the identification of the specific cit-proteins targeted by individual RA sera.

Prevalence and Risk Factors of Substance Use Disorder in Rheumatoid Arthritis.

OBJECTIVE: In this study, we aimed to determine the lifetime prevalence of substance use disorder (SUD) in a Canadian rheumatoid arthritis (RA) cohort and factors associated with SUD in RA. METHODS: Participants with RA (N = 154) were recruited via rheumatology clinics as part of a larger cohort study of psychiatric comorbidity in immune-mediated inflammatory diseases. SUD is defined as the uncontrolled use of a substance despite the harmful consequences of its use. To identify lifetime SUD, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was administered to participants. Participants' sociodemographic and RA clinical characteristics were also assessed. We examined factors associated with lifetime SUD using unadjusted and adjusted logistic regression modeling. RESULTS: Twenty-three (14.9%) of 154 participants with RA met the criteria for a lifetime diagnosis of SUD. The majority of the participants were women, were White, had postsecondary education, and were on a disease-modifying antirheumatic drug. Factors associated with increased odds of SUD were male sex (adjusted odds ratio [aOR]: 3.63, 95% confidence interval [CI]: 1.03-12.73), younger age (aOR: 0.94, 95% CI: 0.90-0.98), and ever smoking (aOR: 6.44, 95% CI: 1.53-27.07). CONCLUSION: We found that approximately 1 in 7 individuals with RA had a lifetime diagnosis of SUD, highlighting the importance of identifying and treating SUD in those with RA. In particular, the following factors were associated with higher odds of SUD: male sex, younger age, and smoking behaviors.

Effect of comorbid mood and anxiety disorders on breast and cervical cancer screening in immune-mediated inflammatory disease.

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.

Impact of Psychiatric Comorbidity on Health Care Use in Rheumatoid Arthritis: A Population-Based Study.

OBJECTIVE: Psychiatric comorbidity is frequent in rheumatoid arthritis (RA) and complicates treatment. The present study was undertaken to describe the impact of psychiatric comorbidity on health care use (utilization) in RA. METHODS: We accessed administrative health data (1984-2016) and identified a prevalent cohort with diagnosed RA. Cases of RA (n = 12,984) were matched for age, sex, and region of residence with 5 controls (CNT) per case (n = 64,510). Within each cohort, we identified psychiatric morbidities (depression, anxiety, bipolar disorder, and schizophrenia [PSYC]), with active PSYC defined as ≥2 visits per year. For the years 2006-2016, annual rates of ambulatory care visits (mean ± SD per person) categorized by provider (family physician [FP], rheumatologist, psychiatrist, other specialist), hospitalization (% of cohort), days of hospitalization (mean ± SD), and dispensed drug types (mean ± SD per person) were compared among 4 groups (CNT, CNT plus PSYC, RA, and RA plus PSYC) using generalized linear models adjusted for age, sex, rural versus urban residence, income quintile, and total comorbidities. Estimated rates are reported with 95% confidence intervals (95% CIs). We tested within-person and RA-PSYC interaction effects. RESULTS: Subjects with RA were mainly female (72%) and urban residents (59%), with a mean ± SD age of 54 ± 16 years. Compared to RA without PSYC, RA with PSYC had more than additive (synergistic) visits (standardized mean difference [SMD] 10.92 [95% CI 10.25, 11.58]), hospitalizations (SMD 13% [95% CI 0.11, 0.14]), and hospital days (SMD 3.63 [95% CI 3.06, 4.19]) and were dispensed 6.85 more medication types (95% CI 6.43, 7.27). Cases of RA plus PSYC had increased visits to FPs (an additional SMD 8.92 [95% CI 8.35, 9.46] visits). PSYC increased utilization in within-person models. CONCLUSION: Managing psychiatric comorbidity effectively may reduce utilization in RA.

Validity and Reliability of Screening Measures for Depression and Anxiety Disorders in Rheumatoid Arthritis.

OBJECTIVE: To test the validity and reliability of screening instruments for depression and anxiety in rheumatoid arthritis (RA). METHODS: Participants with RA completed the Patient Health Questionnaire (PHQ-2 or PHQ-9), the Patient Reported Outcomes Measurement Information System depression short form 8a and anxiety short form 8a, the Hospital Anxiety and Depression Scale anxiety score (HADS-A) and depression score (HADS-D), the Overall Anxiety Severity and Impairment Scale, the Generalized Anxiety Disorder 2- and 7-item scales, and the Kessler-6 scale. Clinical depression and anxiety disorders were confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I Disorders (SCID-1) research version. We reported sensitivity, specificity, positive predictive value, and negative predictive value using SCID-1 diagnoses as the criterion standard. Test-retest reliability was assessed with the intraclass correlation coefficient. RESULTS: Of 150 participants, 11.3% had SCID-1-diagnosed depression, 7.3% had SCID-1-diagnosed generalized anxiety disorder, and 19.3% had any SCID-1-diagnosed anxiety disorder. For depression, sensitivity ranged from HADS-D (cut point 11; 35%) to PHQ-2 (88%) and PHQ-9 (87%). Specificity ranged from PHQ-9 (77%) and PHQ-2 (84%) to HADS-D (cut point 11; 94%). Positive predictive value ranged from 30% to 43%. Negative predictive value ranged from 92% to 98%. For generalized anxiety disorder, sensitivity ranged from HADS-A (cut point 11; 45%) to HADS-A (cut point 8; 91%). Specificity ranged from 81% to 89% for all measures except the HADS-A (cut point 8; 63%). Intraclass correlation coefficient estimates ranging from 0.69 to 0.88 confirmed good test-retest reliability. CONCLUSION: Depression screening instruments had good diagnostic performance; anxiety instruments were more variable. Identified depression and anxiety require clinical confirmation.

Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients.

OBJECTIVES: Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. METHODS: Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. RESULTS: Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5-6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable. CONCLUSION: Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.

A quarter of patients time their early rheumatoid arthritis onset differently than physicians.

Objective: Early rheumatoid arthritis (RA) treatment requires timely recognition. This large, multicentre study compared patient-reported vs physician-reported onset of early RA. Methods: Patients from the Canadian Early ArThritis CoHort with early/suspected RA (persistent synovitis <1 year) completed questionnaires asking about the date of symptom onset; and rheumatologists date of onset for persistent synovitis. Groups with similar reported timing (patient and physician) versus differing timing of 30 days or more were compared. Results: In 2683 patients, the median patient symptom duration (IQR) was 178 days (163) and physician-reported duration was 166 (138). 1940 (72%) patients had similar patient-reported and physician-reported onset (<30 days), whereas 497 (18%) reported onset 30 or more days preceding physicians, and 246 (9%) 30 or more days after physicians. Patients reporting onset preceding physicians had lower baseline Disease Activity Score based on 28 joint count, swollen joint counts and erythrocyte sedimentation rate (p<0.05). Patients reporting onset after physicians were more likely to be rheumatoid factor positive (p<0.001) and had higher anticitrullinated protein antibody titres (p<0.009). Regression showed low income, smoking, fibromyalgia, osteoarthritis and baseline non-methotrexate non-biological disease-modifying antirheumatic drug use were predictors for longer patient-reported symptoms. At 12 months, patients reporting longer symptom duration than physicians had lower rates of Simplified Disease Activity Index remission and higher physician global assessments. Conclusion: Over one-fourth of patients reported differences of >1 month in symptom onset from their rheumatologist. Patients with longer symptom durations had less improvement at 1 year, which may be reflective of comorbid musculoskeletal conditions.

Human host defence peptide LL37 and anti-cyclic citrullinated peptide antibody in early inflammatory arthritis.

Objective: Antibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a major source of citrullinated antigens and the immunomodulatory host defence peptide LL-37. Vitamin D regulates LL-37 expression. This study assessed the associations of LL-37 and anti-CCP, vitamin D metabolites and vitamin D receptor (VDR) polymorphisms in early inflammatory arthritis (EIA). Methods: Serum LL-37, 25-hydroxy-vitamin D (25OHvitD) and anti-CCP were measured by ELISA in treatment naïve EIA (n = 181). VDR single nucleotide polymorphisms (Fok1, Bsm1, Apa1, Taq1, Cdx-2) and HLADRB1 shared epitope (SE) alleles were detected by DNA amplification. Associations were tested in multivariable models. Median (25%, 75%) or percentiles are reported. Results: Participants (70 % female, age 56 [45, 66] years, disease activity score [DAS28ESR3var] 3.7 [2.8, 4.8], 41 % anti-CCP positive, 68 % RA) had low serum 25OHvitD; 20.5 nmol/L (13.9, 29.0). In multivariable models, controlling for age, sex, SE, smoking and vitamin D deficiency, LL37 level (top quartile) associated with anti-CCP seropositivity (OR 22; 95% CI 4 to 104). Conclusions: Levels of circulating LL-37 are associated with anti-CCP seropositivity. LL37 activity may be one mechanism linking infection and toxin exposure to anti-CCP generation.

The Validity and Reliability of Screening Measures for Depression and Anxiety Disorders in Inflammatory Bowel Disease.

BACKGROUND: We evaluated the validity and reliability of multiple symptom scales for depression and anxiety for persons with inflammatory bowel disease (IBD). METHODS: IBD participants in a cohort study completed a Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed the Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Kessler-6 Distress Scale, PROMIS Emotional Distress Depression Short-Form 8a (PROMIS Depression) and Anxiety Short-Form 8a (PROMIS Anxiety), Generalized Anxiety Disorder 7-item Scale, and Overall Anxiety and Severity Impairment Scale. We computed sensitivity, specificity, and positive and negative predictive values for the screening measures with the SCID diagnoses as the reference standard, conducted receiver operating curve (ROC) analysis, and assessed internal consistency and test-retest reliability. RESULTS: Of 242 participants, the SCID classified 8.7% as having major depression and 17.8% as having anxiety disorders. Among the depression scales, the PHQ-9 had the highest sensitivity (95%). Specificity was generally higher than sensitivity and was highest for the HADS-D (cut-point of 11; 97%). The area under the ROC curve (AUC) did not differ significantly among depression scales. Among the anxiety scales, sensitivity was highest for the PROMIS (79%). Specificity ranged from 82% to 88% for all tools except the HADS-A (cut-point of 8; 65%). The AUC did not differ between depression and anxiety tools. CONCLUSIONS: Overall, the symptom scales for depression and anxiety were similar in their psychometric properties. The anxiety scales did not perform as well as the depression scales. Alternate cut-points may be more relevant when these scales are used in an IBD sample.

Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. METHODS: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. RESULTS: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). CONCLUSIONS: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.

Overweight, Obesity, and the Likelihood of Achieving Sustained Remission in Early Rheumatoid Arthritis: Results From a Multicenter Prospective Cohort Study.

OBJECTIVE: Obesity is implicated in rheumatoid arthritis (RA) development, severity, outcomes, and treatment response. We estimated the independent effects of overweight and obesity on ability to achieve sustained remission (sREM) in the 3 years following RA diagnosis. METHODS: Data were from the Canadian Early Arthritis Cohort, a multicenter observational trial of early RA patients treated by rheumatologists using guideline-based care. sREM was defined as Disease Activity Score in 28 joints (DAS28) <2.6 for 2 consecutive visits. Patients were stratified by body mass index (BMI) as healthy (18.5-24.9 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥30 kg/m2 ). Cox regression was used to estimate the effect of the BMI category on the probability of achieving sREM over the first 3 years, controlling for age, sex, race, education, RA duration, smoking status, comorbidities, baseline DAS28, Health Assessment Questionnaire disability index, C-reactive protein level, and initial treatment. RESULTS: Of 982 patients, 315 (32%) had a healthy BMI, 343 (35%) were overweight, and 324 (33%) were obese; 355 (36%) achieved sREM within 3 years. Initial treatment did not differ by BMI category. Compared to healthy BMI, overweight patients (hazard ratio [HR] 0.75 [95% confidence interval (95% CI) 0.58-0.98]) and obese patients (HR 0.53 [95% CI 0.39-0.71]) were significantly less likely to achieve sREM. CONCLUSION: Rates of overweight and obesity were high (69%) in this early RA cohort. Overweight patients were 25% less likely, and obese patients were 47% less likely, to achieve sREM in the first 3 years, despite similar initial disease-modifying antirheumatic drug treatment and subsequent biologic use. This is the largest study demonstrating the negative impact of excess weight on RA disease activity and supports a call to action to better identify and address this risk in RA patients.

Increased Incidence of Critical Illness in Psoriasis.

BACKGROUND: Psoriasis is associated with an increased risk of comorbid disease. Despite the recognition of increased morbidity in psoriasis, the effects on health care utilisation remain incompletely understood. Little is known about the risk of intensive care unit (ICU) admission in persons with psoriasis. OBJECTIVE: To compare the incidence of ICU admission and post-ICU mortality rates in a psoriasis population compared with a matched population without psoriasis. METHODS: Using population-based administrative data from Manitoba, Canada, we identified 40 930 prevalent cases of psoriasis and an age-, sex-, and geographically matched cohort from the general population (n = 150 210). We compared the incidence of ICU admission between populations using incidence rates and Cox regression models adjusted for age, sex, socioeconomic status, and comorbidity and compared mortality after ICU admission. RESULTS: Among incident psoriasis cases (n = 30 150), the cumulative 10-year incidence of ICU admission was 5.6% (95% confidence interval [CI], 5.3%-5.8%), 21% higher than in the matched cohort (incidence rate ratio, 1.21; 95% CI, 1.15-1.27). In the prevalent psoriasis cohort, crude mortality in the ICU was 11.5% (95% CI, 9.9%-13.0%), 32% higher than observed in the matched population admitted to the ICU (8.7%; 95% CI, 8.3%-9.1%). Mortality rates after ICU admission remained elevated at all time points in the psoriasis cohort compared with the matched cohort. CONCLUSION: Psoriasis is associated with an increased risk for ICU admission and with an increased risk of mortality post-ICU admission.

Reduction in Serum Uric Acid May Be Related to Methotrexate Efficacy in Early Rheumatoid Arthritis: Data from the Canadian Early Arthritis Cohort (CATCH).

OBJECTIVES: The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase adenosine levels by blocking its conversion to uric acid (UA). This study was done to determine if methotrexate lowers UA in early RA (ERA). METHODS: Data were obtained from Canadian Early Arthritis Cohort, an incident ERA cohort. All ERA patients with serial UA measurements were included, comparing those with methotrexate use vs. no methotrexate exposure (controls). Analyses were exploratory. Patients with concomitant gout or taking UA-lowering therapies were excluded. RESULTS: In total, 49 of the 2,524 ERA patients were identified with data available for both pre-methotrexate UA levels and post-methotrexate UA levels (300 µmol/L and 273 µmol/L, respectively; P = 0.035). The control group not taking methotrexate had a mean baseline UA level of 280 µmol/L and a follow-up level of 282 µmol/L (P = 0.448); mean change in UA with methotrexate was -26.8 µmol/L vs. 2.3 µmol/L in the no methotrexate group (P = 0.042). Methotrexate users with a decrease in UA had a disease activity score of 2.37 for 28 joints when compared with the controls (3.26) at 18 months (P = 0.042). Methotrexate users with decreased UA had a lower swollen joint count (SJC) of 0.9 at 18 months, whereas methotrexate users without lowering of UA had an SJC of 4.5 (P = 0.035). Other analyses were not significant. CONCLUSIONS: Methotrexate response is associated with lowering of serum UA in ERA compared to nonusers. This may be due to changes in adenosine levels. Methotrexate response is associated with lower UA and fewer swollen joints compared to nonresponders.

Effects of Rituximab and Infliximab Treatment on Carboxypeptidase B and Its Substrates in RA Synovium.

OBJECTIVE: We evaluated the synovial effects of 2 potent biologic rheumatoid arthritis (RA) therapies, focusing on their effect on the expression level of carboxypeptidase B (CPB) and its substrates. METHODS: Patients with RA receiving infliximab (IFX; n = 9) or rituximab (RTX; n = 5) had an arthroscopic synovial biopsy at baseline and 16 weeks posttherapy. Expression of CPB, C5a, osteopontin (OPN), CD3, CD20, CD55, and CD68 was assessed by immunohistochemistry and image analysis, and compared with OA synovium. RA disease activity score was assessed at multiple timepoints. Serial serum samples were analyzed for soluble CPB and C5a levels. RESULTS: The baseline clinical characteristics of patients receiving IFX and RTX were similar. At the time of the second biopsy, 50% of patients had achieved a European League Against Rheumatism good or moderate response. At baseline, expression of CPB, C5a, and OPN was markedly higher in RA compared with OA synovium and correlated with mononuclear cell infiltration. There was an overall reduction in synovial expression of CPB, C5a, and OPN paralleling a reduction in mononuclear cell infiltration, but these changes were not associated with clinical response. After an early reduction in serum C5a levels, these returned to baseline levels at later timepoints. CONCLUSION: In response to IFX and RTX treatment, RA synovial expression of CPB, C5a, and OPN decrease independently of the clinical response, reflecting the complex proinflammatory and antiinflammatory effects of this pathway.

Missing Anticitrullinated Protein Antibody Does Not Affect Short-term Outcomes in Early Inflammatory Arthritis: From the Canadian Early Arthritis Cohort.

OBJECTIVE: Anticitrullinated protein antibody (ACPA) is as sensitive as, but more specific than, rheumatoid factor (RF) and is detected earlier in rheumatoid arthritis (RA). Although part of the RA classification criteria, ACPA testing is not routinely paid for/accessible in all jurisdictions. The effect of missing ACPA testing was studied to determine whether failure to perform ACPA testing could cause a care gap in early inflammatory arthritis. METHODS: Nearly 2000 patients (n = 1998) recruited to an early inflammatory arthritis cohort were allocated into 3 groups: (1) seropositive (either RF+ or ACPA+), (2) seronegative (RF- and ACPA-), and (3) missing ACPA and RF-. Analyses were adjusted for age, sex, symptom duration, and smoking status if p < 0.1. Disease Activity Score at 28 joints (DAS28) at 3 months was studied, because beyond then, disease activity is expected to determine ongoing treatment. RESULTS: More seropositive patients fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism RA criteria than seronegative patients. Group 3 was slightly older and had a smaller percentage of females, as well as shorter symptom duration and less smoking. At 3 months, group 3 was treated with fewer disease-modifying antirheumatic drugs and methotrexate (p < 0.00002) than groups 1 and 2, but there were no significant differences in DAS28, Health Assessment Questionnaire-Disability Index (HAQ-DI), proportion receiving corticosteroids, or physician's/patient's global assessments. CONCLUSION: There was no care gap in the RF-negative, unknown ACPA group because there were no significant differences in the DAS28, 3-month change in DAS28, or HAQ-DI, despite less treatment. Cost-effectiveness of ensuring ACPA testing availability in suspected RA is unknown because early outcomes did not differ, whether or not ACPA was available.