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Aims To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP). Methods and results The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014–19. The treatment goal for BP was Conclusion We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.

OBJECTIVE To determine whether childhood maltreatment is associated with immune-mediated inflammatory disorders (IMID; multiple sclerosis [MS], inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]). We further aimed to determine the relationship between maltreatment and psychiatric comorbidity in IMID and whether these relationships differed across IMID. METHODS 681 participants (MS: 232, IBD: 216, RA: 130, healthy controls: 103) completed a structured psychiatric interview to identify psychiatric disorders, and the Childhood Trauma Questionnaire to evaluate five types of maltreatment: emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect. We evaluated associations between maltreatment, IMID and psychiatric comorbidity using multivariable logistic regression models. RESULTS The prevalence of having ≥1 maltreatment was similar across IMID, but higher than in controls (MS: 63.8%, IBD: 61.6%, RA: 62.3%, healthy controls: 45.6%). Emotional abuse was associated with having an IMID (adjusted odds ratio [aOR] 2.37; 1.15-4.89). In the sex-specific analysis, this association was only present in women. History of childhood maltreatment was associated with a lifetime diagnosis of a psychiatric disorder in the IMID cohort (OR 2.24; 1.58-3.16), but this association did not differ across diseases. In those with IMID, total types of maltreatments (aOR 1.36; 1.17-1.59) and emotional abuse (aOR 2.64; 1.66-4.21) were associated with psychiatric comorbidity. CONCLUSIONS Childhood maltreatment is more common in IMID than in a healthy population, and is associated with psychiatric comorbidity. Given the high burden of psychiatric disorders in the IMID population, clinicians should be aware of the contribution of maltreatment and the potential need for trauma-informed care strategies.

The association of taste genetics and the oral microbiome in autoimmune diseases such as rheumatoid arthritis (RA) has not been reported. We explored a novel oral mucosal innate immune pathway involving the bitter taste G protein-coupled receptor T2R38. This case–control study aimed to evaluate whether T2R38 polymorphisms associate with the buccal microbial composition in RA. Genomic DNA was obtained from buccal swabs of 35 RA patients and 64 non-RA controls. TAS2R38 genotypes were determined by Sanger sequencing. The buccal microbiome was assessed by Illumina MiSeq sequencing of the V4-16S rRNA gene. Bacterial community differences were analyzed with alpha and beta diversity measures. Linear discriminant analysis effect size identified taxa discriminating between RA versus non-RA and across TAS2R38 genotypes. TAS2R38 genotype frequency was similar between RA and non-RA controls (PAV/PAV, PAV/AVI, AVI/AVI: RA 42.9%, 45.7%, 11.4% versus controls 32.8%, 48.4%, 18.8%, chi-square (2, N = 99) = 2.1, p = 0.35). The relative abundance of Porphyromonas, among others, differed between RA and non-RA controls. The relative abundance of several bacterial species also differed across TAS2R38 genotypes. These findings suggest an association between T2R38 polymorphisms and RA buccal microbial composition. However, further research is needed to understand the impact of T2R38 in oral health and RA development.

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.

Objective Guidelines for methotrexate (MTX) use in rheumatic disease may not be feasible for physicians practicing in the least developed countries. We aimed to understand the experiences of MTX prescribers relating to MTX use for rheumatic disease in African countries to inform the development of culturally and geographically appropriate recommendations. Methods African physicians who self‐identified as MTX prescribers from countries classified as having a low versus a medium or high Human Development Index (L‐HDI versus MH‐HDI) participated in semistructured interviews between August 2016 and September 2017. Interviews were transcribed verbatim, coded thematically, and stratified by HDI. Results Physicians (23 rheumatologists; six internists) from 29 African countries were interviewed (15 L‐HDI; 14 MH‐HDI). Identified barriers to MTX use included inconsistent MTX supply (reported by 87% L‐HDI versus 43% MH‐HDI), compounded by financial restrictions (reported by 93% L‐HDI versus 64% MH‐HDI), patient hesitancy based partly on cultural beliefs and societal roles (reported by 71%), few prescribers (reported by 33%), prevalent infections (especially viral hepatitis, tuberculosis, and human immunodeficiency virus), and both availability and cost of monitoring tests. MTX pretreatment evaluation and starting and maximal doses were similar between L‐HDI countries and MH‐HDI countries. Conclusion The challenges of treating rheumatic disease in African countries include unreliable drug availability and cost, limited subspecialists, and patient beliefs. Adapting recommendations for MTX use in the context of prevalent endemic infections; ensuring safe but feasible MTX monitoring strategies, enhanced access to stable drug supply, and specialized rheumatology care; and improving patient education are key to reducing the burden of rheumatic diseases in L‐HDI countries.

Background Individuals with immune-mediated inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, are at increased risk for influenza and related complications. We examined and compared the uptake of influenza vaccination among people with and without these diseases, as well as the influence of psychiatric comorbidity on vaccine uptake. Methods Using administrative data from Apr. 1, 1984, to Mar. 31, 2016, we conducted a retrospective matched cohort study in Manitoba, Canada. We matched persons 18 years of age or older who had a diagnosis of inflammatory bowel disease, multiple sclerosis or rheumatoid arthritis (the immune-mediated inflammatory disease cohorts) with persons who did not have these diagnoses (the control cohorts) on age, sex and region. We then identified cohort members with any mood or anxiety disorder (depression, anxiety disorders, bipolar disorder). We identified influenza vaccinations through billing codes. Using binomial regression, we modelled the difference in the proportion of the immune-mediated inflammatory disease and matched cohorts vaccinated annually, with adjustment for sociodemographic characteristics, comorbidity and immune therapy. We tested additive interaction effects between a person's cohort and presence of a mood or anxiety disorder. Results We identified 32 880 individuals with 1 or more immune-mediated inflammatory diseases (10 148 with inflammatory bowel disease, 6158 with multiple sclerosis and 16 975 with rheumatoid arthritis) and a total of 164 152 controls. In fiscal year 2015, 8668 (41.3%, 95% confidence interval [CI] 40.6% to 42.0%) of the 20 982 persons with an immune-mediated inflammatory disease received an influenza vaccination, a rate higher than among controls (35 238 of 104 634; 33.7%, 95% CI 33.4% to 34.0%). After adjustment, participants with an immune-mediated inflammatory disease but no mood or anxiety disorder had 6.44% (95% CI 5.79% to 7.10%) greater uptake of vaccination than participants without such a disease. Among participants without an immune-mediated inflammatory disease, having a mood or anxiety disorder was associated with 4.54% (95% CI 4.20% to 4.89%) greater uptake of vaccination. However, we observed a subadditive interaction between immune-mediated inflammatory disease and psychiatric status (-1.38%, 95% CI -2.26% to -0.50%). Interpretation Uptake of influenza vaccination was consistently low in populations with immune-mediated inflammatory disease, and although psychiatric morbidity is associated with greater vaccine uptake by Manitobans, it negatively interacts with these diseases to reduce uptake. Changes in care delivery are needed to mitigate this gap in care.

ObjectiveTo test the association of early disease severity with grade 12 standards test performance in individuals with childhood-onset chronic rheumatic diseases (ChildCRDs), including juvenile arthritis and systemic autoimmune rheumatic diseases.MethodsWe used linked provincial administrative data to identify patients with ChildCRDs born between 1979 and 1998 in Manitoba, Canada. Primary outcomes were Language and Arts Achievement Index (LAI) scores and Math Achievement Index (MAI) scores from grade 12 standards test results as well as enrollment data. The secondary outcome was enrollment in grade 12 by 17 years of age. Latent class trajectory analysis identified disease severity groups using physician visits following diagnosis. Multivariable linear regression tested the association of disease severity groups with LAI and MAI scores, and logistic regression tested the association of disease severity with age-appropriate enrollment, after adjusting for sociodemographic factors and psychiatric morbidities.ResultsThe study cohort included 541 patients, 70.1% of whom were female. A 3-class trajectory model provided the best fit; it classified 9.7% of patients as having severe disease, 54.5% as having moderate disease, and 35.8% as having mild disease. After covariate adjustment, severe disease was associated with poorer LAI and MAI scores but not with age-appropriate enrollment.ConclusionAmong patients with ChildCRDs, those with severe disease performed more poorly on grade 12 standards tests, independent of sociodemographic and psychiatric risk factors. Clinicians should work with educators and policy makers to advocate for supports to improve educational outcomes of patients with ChildCRDs.

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.

OBJECTIVE Higher self-reported disability (high Health Assessment Questionnaire [HAQ] score) has been associated with hospitalizations and mortality in established rheumatoid arthritis (RA), but associations in early RA are unknown. METHODS Patients with early RA (symptom duration

Background Inflammatory bowel disease (IBD) is associated with an increase in psychiatric comorbidity (PC) compared with the general population. We aimed to determine the impact of PC on health care utilization in persons with IBD. Methods We applied a validated administrative definition of IBD to identify all Manitobans with IBD from April 1, 2006, to March 31, 2016, and a matched cohort without IBD. A validated definition for PC in IBD population was applied to both cohorts; active PC status meant ≥2 visits for psychiatric diagnoses within a given year. We examined the association of active PC with physician visits, inpatient hospital days, proportion with inpatient hospitalization, and use of prescription IBD medications in the following year. We tested for the presence of a 2-way interaction between cohort and PC status. Results Our study matched 8459 persons with IBD to 40,375 controls. On crude analysis, IBD subjects had ≥3.7 additional physician visits, had >1.5 extra hospital days, and used 2.1 more drug types annually than controls. Subjects with active PC had >10 more physician visits, had 3.1 more hospital days, and used >6.3 more drugs. There was a synergistic effect of IBD (vs no IBD) and PC (vs no PC) across psychiatric disorders of around 4%. This synergistic effect was greatest for anxiety (6% [2%, 9%]). After excluding psychiatry-related visits and psychiatry-related hospital stays, there remained an excess health care utilization in persons with IBD and PC. Conclusion Inflammatory bowel disease with PC increases health care utilization compared with matched controls and compared with persons with IBD without PC. Active PC further increases health care utilization.

We estimated the incidence and prevalence of benzodiazepine and Z-drug (separately and jointly as BZD) use in the inflammatory bowel disease (IBD) population compared with matched controls without IBD and examined the association of mood/anxiety disorders (M/ADs) with the use of BZD from 1997 to 2017.Using administrative data from Manitoba, Canada, we identified 5,741 persons with incident IBD who were matched in a 1:5 ratio to controls on sex, birth year, and region. Validated case definitions were used to identify M/AD. Dispensations of BZD were identified. Multivariable generalized linear models were used to assess the association between IBD, M/AD, and BZD use.In 2016, the incident age/sex-standardized benzodiazepine use rates per 1,000 were 28.06 (95% confidence interval [CI] 26.41-29.81) in the IBD cohort and 16.83 (95% CI 16.28-17.39) in controls (adjusted rate ratio = 1.69 [95% CI 1.56-1.79]). Benzodiazepine incidence rates were higher for women with IBD than men, but the RR between cases and controls were similar for men and women. The incident age/sex-standardized Z-drug use rate per 1,000 was 21.07 (95% CI 19.69-22.41) in the IBD cohort. This was 1.87-fold higher than in controls (95% CI 1.73-2.01). In 2017, approximately 20% of persons with IBD used benzodiazepines and 20% used Z-drugs. There was a subadditive effect of both benzodiazepine and Z-drug uses between IBD and M/AD after adjusting for covariates.The use of BZD is more common in people with IBD than in population controls. Strategies to reduce the use of BZDs in persons with IBD and to offer alternative management strategies for M/ADs, sleep disorders, and other symptomatic concerns are needed.

Background: Little is known about the effects of changes in the presence or absence of psychiatric disorders on health care utilization in multiple sclerosis (MS). Objective: To evaluate the association between “active” mood and anxiety disorders (MAD) and health care utilization in MS. Methods: Using administrative data from Manitoba, Canada, we identified 4748 persons with MS and 24,154 persons without MS matched on sex, birth year, and region. Using multivariable general linear models, we evaluated the within-person and between-person effects of any “active” MAD on annual physician visits, hospital days, and number of drug classes dispensed in the following year. Results: Annually, the MS cohort had an additional two physician visits, two drug classes, and nearly two more hospital days versus the matched cohort. Individuals with any MAD had more physician visits, had hospital days, and used more drug classes than individuals without a MAD. Within individuals, having an “active” MAD was associated with more utilization for all outcomes than not having an “active” MAD, but the magnitude of this effect was much smaller for visits and drugs than the between-person effect. Conclusion: Within individuals with MS, changes in MAD activity are associated with changes in health services use.

Background: Longitudinal studies assessing depression and anxiety effects on cognition in multiple sclerosis (MS) are limited. Objective: We tested whether within-person fluctuations in symptoms of depression or anxiety over time affect cognition in persons with MS, inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and a lifetime history of depression/anxiety disorders (DEP/ANX) but without an immune-mediated inflammatory diseases (IMID). Methods: We followed participants (MS: 255, IBD: 247, RA: 154, and DEP/ANX: 306) for 3 years. Annually, they completed the hospital anxiety and depression scale (HADS) and cognitive tests including the symbol digit modalities test (SDMT). We evaluated associations of elevated symptoms (scores ⩾ 11) of anxiety (HADS-A) and depression (HADS-D) with SDMT z-scores using multivariable linear models—estimating between-person and within-person effects. Results: Participants with MS performed worse on the SDMT than participants in the DEP/ANX cohort (β = −0.68; 95% CI: −0.88, −0.48). Participants with elevated HADS-A scores performed worse on the SDMT than those without elevated scores (β = −0.43; 95% CI: −0.65, −0.21), particularly those with RA. Time-varying within-person elevations in depressive symptoms were associated with worse SDMT performance (β = −0.12; 95% CI: −0.21, −0.021). Conclusions: Across persons, elevated symptoms of anxiety adversely affected information processing. Elevated symptoms of depression within-persons over time were associated with declines in information processing speed.

Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries. It is unknown whether they are relevant globally. We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs).Electronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. Reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for study quality assessment. Similarities and discrepancies of recommendations are reported.After deduplication, 1693 unique citations were found; 25 full texts were screened and 12 included in the narrative synthesis. Average scores for the AGREE II domains ranged from 33.3 to 83.3%. Recommendations targeted rheumatologists and health care providers involved in RA care. Most covered some but not all of the following areas: baseline "pre-MTX" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). Recommendations agreed on baseline tests prior to starting MTX, monitoring, and need for folic acid supplementation. These aspects can serve as the foundation for the development of MTX recommendations relevant to LDCs. Recommendations disagreed on the MTX starting dose, optimal route, titration, and intervals to monitor toxicity.Existing recommendations do not uniformly address all aspects related to the use of MTX and disagree in relevant aspects of MTX use. Adaptations to these recommendations are needed to facilitate their implementation in LDCs. Key Points • This paper summarizes current recommendations on the use of methotrexate for the treatment of rheumatoid arthritis. • Areas of agreement between recommendations include the following: pre-methotrexate patient assessment, need for folic acid supplementation, and toxicity monitoring. • Areas of disagreement relate to methotrexate starting and maximal dose, titration, and frequency of assessments.

ObjectiveThe aims of this study were (1) to compare grade 12 standardized test results of patients diagnosed with childhood-onset chronic rheumatic diseases (ChildCRD) and unaffected peers; and (2) to identify factors associated with test results of patients with ChildCRD and unaffected peers.MethodsThis was a population-based retrospective cohort study. All patients with ChildCRD (juvenile arthritis and systemic autoimmune rheumatic diseases) from the only pediatric rheumatology center in Manitoba for birth cohorts January 1979 to December 1998 were linked to the provincial administrative databases containing records of healthcare use and education outcomes. Patients were matched by age, sex, and postal codes to their peers who did not have ChildCRD. The primary outcomes were the grade 12 Language Arts Achievement Index (LAI) and the Math Achievement Index (MAI) scores. ChildCRD, sociodemographic, and mental health factors were tested for their associations with LAI and MAI scores using multivariable linear regression.ResultsFive hundred and forty-one patients with ChildCRD were matched to 2713 unaffected peers. Patients with ChildCRD had lower LAI and MAI scores compared to their peers. More patients with ChildCRD failed or did not take the language arts (51% vs 41%, P < 0.001) and math (61% vs 55%, P = 0.02) tests. On multivariable analysis, ChildCRD, lower socioeconomic status, younger maternal age at first childbirth, family income assistance, involvement with child welfare services, and mental health morbidities (between ChildCRD diagnosis and standardized testing), were associated with worse LAI and MAI results.ConclusionThis population-based study showed that patients with ChildCRD performed less well than their peers on grade 12 standardized testing, independent of sociodemographic and mental health comorbidities.

ObjectiveTo develop guidance on the use of coronavirus disease 2019 (COVID-19) vaccines in patients with autoimmune rheumatic diseases (ARD).MethodsThe Canadian Rheumatology Association (CRA) formed a multidisciplinary panel including rheumatologists, researchers, methodologists, vaccine experts, and patients. The panel used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Outcomes were prioritized according to their importance for patients and clinicians. Evidence from the COVID-19 clinical trials was summarized. Indirect evidence for non–COVID-19 vaccines in ARD was also considered. The GRADE evidence-to-decision (EtD) framework was used to develop a recommendation for the use of the 4 COVID-19 vaccines approved in Canada as of March 25, 2021 (BNT162b2, mRNA-1273, ChAdOx1, and Ad26.COV2.S), over 4 virtual panel meetings.ResultsThe CRA guideline panel suggests using COVID-19 vaccination in persons with ARD. The panel unanimously agreed that for the majority of patients, the potential health benefits of vaccination outweigh the potential harms in people with ARDs. The recommendation was graded as conditional because of low or very low certainty of the evidence on the effects in the population of interest, primarily due to indirectness and imprecise effect estimates. The panel felt strongly that persons with autoimmune rheumatic diseases who meet local eligibility should not be required to take additional steps compared to people without ARDs to obtain their vaccination. Guidance on medications, implementation, monitoring of vaccine uptake, and research priorities are also provided.ConclusionThis recommendation will be updated over time as new evidence emerges, with the latest recommendation, evidence summaries, and EtD available on the CRA website.

Introduction: Rates of periodontal disease and tooth loss are increased in individuals with rheumatoid arthritis (RA). Understanding factors that contribute to the increased burden of periodontal disease in RA is critical to improving oral health and arthritis outcomes. Objectives: To determine the perceptions held by people with RA relating to their oral health, to identify patient-centered priorities for oral health research, and to inform optimal strategies for delivering oral health knowledge. Methods: Semistructured interviews were conducted with patients with RA. Recorded interview transcripts were iteratively reviewed to reveal surface and latent meaning and to code for themes. Constructs were considered saturated when no new themes were identified in subsequent interviews. We report themes with representative quotes. Results: Interviews were conducted with 11 individuals with RA (10 women [91%]; mean age, 68 y), all of whom were taking RA medication. Interviews averaged 19 min (range, 8 to 31 min) and were mostly conducted face-to-face. Three overall themes were identified: 1) knowledge about arthritis and oral health links; 2) oral health care in RA is complicated, both in personal hygiene practices and in professional oral care; and 3) poor oral health is a source of shame. Participants preferred to receive oral health education from their rheumatologists or dentists. Conclusions: People with RA have unique oral health perceptions and experience significant challenges with oral health care due to their arthritis. Adapting oral hygiene recommendations and professional oral care delivery to the needs of those with arthritis are patient priorities and are required to improve satisfaction regarding their oral health. Knowledge Translation Statement: Patients living with long-standing rheumatoid arthritis described poor oral health–related quality of life and multiple challenges with maintaining optimal oral health. Study findings indicate a need for educational materials addressing oral health maintenance for patients with rheumatic diseases and their providers.

Objective We assessed the information needs of persons with any of three immune-mediated inflammatory diseases (multiple sclerosis [ MS], inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) regarding depression, as a first step toward developing patient-relevant information resources, ultimately to facilitate self-management and appropriate care. We also compared information needs across genders. Methods We surveyed participants with MS, IBD and RA regarding depression-related information needs including types of treatments, effectiveness, risks, benefits, and perceived helpfulness of treatments. We compared responses between groups using multivariate regression. Results 328 participants provided complete responses (MS: 141, IBD: 114, RA: 73). Most of the topics queried were perceived as very important, and similarly important for all groups. Women placed higher importance than men on most topics. The most popular formats for receiving information were discussion with a counselor (very preferred: 67.4%) and written information (very preferred: 65.5%); this did not differ between groups. Conclusions Persons affected by MS, IBD and RA are interested in receiving information about multiple topics related to depression treatment, from multiple sources. Women desire more information than men. Practice implications These findings can be used to design information resources to meet information needs regarding depression in MS, IBD and RA.

Objective Metabolic syndrome (MetS) prevalence in early rheumatoid arthritis (ERA) is conflicting. The impact of sex, including menopause, has not been described. We estimated the prevalence and factors associated with MetS in men and women with ERA. Methods A cross‐sectional study of the Canadian Early Arthritis Cohort (CATCH) was performed. Participants with baseline data to estimate key MetS components were included. Sex‐stratified logistic regression identified baseline variables associated with MetS. Results The sample included 1543 participants; 71% were female and the mean age was 54 (SD 15) years. MetS prevalence was higher in men 188 (42%) than women 288 (26%, P < 0.0001) and increased with age. Frequent MetS components in men were hypertension (62%), impaired glucose tolerance (IGT, 40%), obesity (36%), and low high‐density lipoprotein cholesterol (36%). Postmenopausal women had greater frequency of hypertension (65%), IGT (32%), and high triglycerides (21%) compared with premenopausal women (P < 0.001). In multivariate analysis, MetS was negatively associated with seropositivity and pulmonary disease in men. Increasing age was associated with MetS in women. In postmenopausal women, corticosteroid use was associated with MetS. Psychiatric comorbidity was associated with MetS in premenopausal women. MetS status was not explained by disease activity or core RA measures. Conclusion The characteristics and associations of MetS differed in men and women with ERA. Sex differences, including postmenopausal status, should be considered in comorbidity screening. With this knowledge, the interplay of MetS, sex, and RA therapeutic response on cardiovascular outcomes should be investigated.

Objective To evaluate seasonal patterns of early inflammatory arthritis (IA) onset and potential associations with IA symptom onset. Methods The Canadian Early Arthritis Cohort (CATCH) is an inception cohort study of adults with early (12 months or less) IA. We used patient reports of symptom onset as a proxy of IA onset and examined the seasonal distribution of IA onset over 10 years. Influenza time series was based on laboratory‐confirmed influenza A and B from the Canadian FluWatch surveillance from 2010‐2016. Bivariate analysis of influenza and IA was performed using cross‐correlations with different time lags and Poisson regression. IA and influenza were recorded as monthly total frequencies. Results Of 2519 IA patients, 88% had confirmed rheumatoid arthritis (RA). Significantly, more IA onsets occurred in winter compared with other seasons (P = 0.03); although IA onset was more frequent in January, the difference between months was not statistically significant. Compared to months with the lowest influenza rates, months with the highest influenza rates had a statistically significant, but trivial, increase of 0.003% in the incidence of IA (incidence rate ratio (95% confidence interval): 1.00003 (1.00005; 1.000053), P = 0.02). Conclusion Although IA symptom onset occurs more frequently in winter, we found that flu outbreaks were not associated with a meaningful increase in IA symptom onset in a large, well‐characterized cohort of Canadian adults over 6 years.

Objective Childhood-onset SLE (cSLE) manifests differently than adult-onset SLE (aSLE). This study determined whether ethnic differences contribute to the differences in clinical presentation between the two groups. Methods This cross-sectional study used data from a multi-centred registry from eight adult and four paediatric Canadian centres gathered at study entry. We compared the frequency of clinical manifestations and autoantibodies between aSLE and cSLE. For those with a significant difference, a multivariable logistic regression was performed, adjusting for ethnicity, SLE onset (cSLE vs aSLE), disease duration and centre. Disease activity and damage between aSLE and cSLE were compared after stratifying by disease duration. Results Of 552 aSLE subjects, 502 (90.9%) were female and 381 (69.0%) were Caucasian. Mean age at diagnosis was 37.0 ± 13.6 years and disease duration 10.9 ± 9.6 years. Of 276 cSLE subjects, 231 (83.7%) were female and 101 (36.6%) were Caucasian. Mean age at diagnosis was 12.7 ± 3.3 years and disease duration 5.6 ± 8.2 years. In multivariable regression analysis, aSLE was associated with decreased odds of having a neurologic disorder (odds ratio = 0.49) and increased odds of having aCL antibodies (odds ratio = 1.85). Disease activity and damage accrual scores were higher in aSLE than cSLE within the same disease duration strata, although the differences were not clinically significant. Ethnicity was not associated with any differences in clinical manifestations or autoantibody frequency between aSLE and cSLE. Conclusion Although a crude comparison of aSLE and cSLE yielded several differences in clinical symptoms and autoantibodies, this difference was not attributable to ethnic differences between aSLE and cSLE.

BACKGROUND The aim of this study was to determine the prevalence, incidence, and onset age at rheumatoid arthritis (RA) diagnosis in First Nations (FN) and non-FN populations in Manitoba, Canada. METHODS Population-based administrative health records from April 1, 1995, to March 31, 2010, were accessed for all Manitobans. The FN population was identified using the Federal Indian Registry File. Crude and adjusted RA prevalence and incidence rates (adjusted for age, sex, health region of residence) were compared using Poisson regression and reported as relative rates (RRs) with 95% confidence intervals (CIs). Mean (CI) diagnosis age and physician visits were compared with Student t tests. RESULTS Rheumatoid arthritis crude prevalence increased between 2000 and 2010 to 0.65%; adjusted RA prevalence in females was 1.0% and in males was 0.53%. The 2009/2010 adjusted RA prevalence was higher in FN than non-FN (RR, 2.55; CI, 2.08-3.12) particularly for ages 29 to 48 years (RR, 4.52; CI, 2.71-7.56). Between 2000 and 2010, crude RA incidence decreased from 46.7/100,000 to 13.4/100,000. Adjusted RA incidence remained higher in FN than non-FN (2000-2010 RR, 2.1; CI, 1.7-2.6; p < 0.0001) particularly for ages 29 to 48 years (RR, 4.6; CI, 2.8-7.4; p < 0.0001). The FN population was younger at diagnosis than the non-FN population (mean age, 39.6 years [CI, 38.3-40.8 years] vs. 53.3 years [CI, 52.7-53.9 years]; p < 0.0001). The FN population had more physician visits but fewer rheumatology visits than the non-FN population. CONCLUSIONS Rheumatoid arthritis prevalence is increasing, and RA incidence is decreasing in Manitoba. The FN population has a greater prevalence and incidence of RA and is younger at diagnosis than the non-FN population. When combined with fewer rheumatology visits, this significant care gap highlights the need to optimize rheumatology care delivery to the FN population.

ObjectiveTo determine whether anxiety and depression are associated with cognition in multiple sclerosis (MS), and whether these associations are similar in other immune-mediated inflammatory diseases (IMID; including inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) and in anxious/depressed individuals (ANX/DEP) without an IMID.MethodsParticipants (MS: n = 255; IBD: n = 247; RA: n = 154; ANX/DEP: n = 308) completed a structured psychiatric interview, the Hospital Anxiety and Depression Scale, and cognitive testing, including the Symbol Digit Modalities Test, the California Verbal Learning Test, and Letter Number Sequencing test. Test scores were converted to age-, sex-, and education-adjusted z scores. We evaluated associations of anxiety and depression with the cognitive z scores using multivariate linear models, adjusting for disease cohort.ResultsAll cohorts exhibited higher rates of impairment (i.e., z less than or equal to −1.5) in the domains of processing speed, verbal learning, and delayed recall memory relative to general population norms. Higher levels of anxiety symptoms were associated with slower processing speed, lower verbal learning, and lower working memory performance (all p < 0.001); higher levels of depression symptoms were associated with slower processing speed. These associations did not differ across cohorts.ConclusionAnxiety and depression are associated with lower cognitive function in MS, with a similar pattern observed in persons with other IMID, including IBD and RA, and persons without an IMID. Managing symptoms of anxiety and of depression in MS, as well as other IMIDs, is important to mitigate their effect on cognition.

Chronic pediatric musculoskeletal (MSK) conditions are a major cause of morbidity. The burden of pediatric rheumatic diseases in East Africa is largely unknown. The purposes of this study were to estimate frequencies and assess the spectrum of MSK-related diagnoses using ICD-10 diagnostic codes among outpatients at a pediatric hospital in Kenya and to evaluate the accuracy of the assigned codes used for the 'arthropathies' category. All pediatric outpatient diagnoses classified under the ICD-10 codes for 'diseases of the MSK system and connective tissue' (M00-M99) recorded between January and December 2011 were extracted from the electronic medical record system at Gertrude's Children's Hospital (GCH). For each of the ten MSK disease categories, frequencies were calculated. The assigned ICD10 code for cases in the 'arthropathies' (M00-M25) category was assessed by two rheumatologists. MSK diagnoses (n = 1078) accounted for 0.5% of all GCH outpatient consults available for analysis. 'Soft tissue disorders' were the most frequent MSK diagnoses (n = 614, 57%), followed by 'arthropathies' (n = 332, 30.8%), 'dorsopathies' (n = 81, 7.5%), 'osteopathies and chondropathies' (n = 39, 3.6%), and 'other' disorders (n = 12, 1.1%). No patients were classified in the category of 'systemic connective tissue disorders'. In cases classified as 'arthropathies', there was poor agreement (Kappa 0.136) between the ICD10 code assigned by the treating physicians and that assigned by the rheumatologists. However, when the rheumatologists' classification was loosened, agreement was moderate (Kappa 0.533). This study provides estimates of the frequency of outpatient MSK diagnoses at a pediatric hospital in Kenya in 2011. MSK diagnoses were not rare. Despite limitations of administrative databases to estimate frequencies of specific diagnoses, they provide a snapshot of the overall burden and spectrum of MSK conditions.

We appreciate the interest in our manuscript concerning the Health Assessment Questionnaire disability index (HAQ) in an early rheumatoid arthritis incident cohort (the CATCH cohort) which predicted all-cause mortality (1). We will clarify queries raised in letters to the editor (2-4).

Background Anxiety is common in patients with rheumatoid arthritis (RA) and associated with worse RA outcomes. This study assessed the feasibility and preliminary health impacts (mental and physical) of a non-therapist assisted, online mental health intervention targeting anxiety in this population. Methods Participants with confirmed RA and elevated anxiety symptoms were enrolled into the Worry and Sadness program, an Internet-based cognitive-behavioral therapy (iCBT) intervention for anxiety and depression shown to be effective in the general population. Validated self-report measures of anxiety, depression, pain interference, fatigue, physical health-related quality of life, functional status, and patient-reported disease severity were collected at baseline, post-intervention, and at three-month follow-up. Emotional distress scores were tracked between lessons. Participants provided qualitative feedback in writing post-intervention. Results We analyzed the responses of 34 participants; the majority was female (86%) and the mean age was 57 (SD = 13). Of these, 80% (n = 28) completed the study in its entirety. Among these completers, 94.1% described the program as worthwhile. We found statistically significant improvements in anxiety, depression and fatigue from baseline to three-month follow-up, with small to large effect sizes (d = 0.39–0.81). Post-hoc analyses revealed that statistically significant change occurred between baseline and post-intervention for anxiety and depression and was maintained at three-month follow-up, whereas statistically significant change occurred between baseline and three-month follow-up for fatigue. Statistically significant reductions in emotional distress occurred across the program, with a large effect size (d = 1.16) between the first and last lesson. Conclusion The Worry and Sadness program shows promise as a feasible resource for improving mental health in RA., Highlights • This study provided support for a non-therapist assisted online intervention for the improvement of anxiety in RA patients. • This online intervention demonstrated a large effect in terms of sustained anxiety reduction for program completers. • The online intervention also demonstrated beneficial effects on depression, emotional distress, and fatigue.

Background:The RA-FQ is a patient-reported measure of current disease activity in RA that can be used to identify disease flares. The RA-FQ queries pain, physical function, fatigue, stiffness, and participation and yields a score from 0-50. We previously reported on reliability, validity, and responsiveness.Objectives:To identify changes in RA-FQ that represent minimal and meaningful improvement or worsening from the perspective of people with RA, treating rheumatologists, and in relation to disease activity indices. We hypothesized thatMethods:Data were from adults with early RA (sx Results:The 808 adults were mostly white (84%) women (71%) with a mean (SD) age of 55 (15) and moderate-high CDAI level (85%) at enrollment. Most (79%) reported their RA had changed; 59% were better and 20% worse. Patients who were a lot worse had a mean increase of 8.9 points whereas those who rated themselves as a lot better had a -6.0 decrease on the RA-FQ (Figure 1). Minimal worsening and improvement were associated with 4.7 and -1.8 change in RA-FQ scores, respectively, while patients who rated their RA unchanged had stable RA-FQ scores (Table 1).Similar changes were evident in CDAI, SDAI, and DAS indices (Table 1). Larger differences were observed with patient vs. physician global scores and tender vs. swollen joints. Across measures, the change associated with worsening was greater than for improvement. Results supported all prespecified hypotheses ab.Table 1.Spearman’s correlation coefficients of PsAQoL with the other parameters for construct validityDomainA Lot Better(N=346; 43%)A Little Better(N=132; 16%)The Same(N=174; 21%)A Little Worse(N=94; 12%)A Lot Worse(N=62; 8%)Δ95% CISDΔ95% CISDΔ95% CISDΔ95% CISDΔ95% CISDRA-FQ Total (0-50)-6.0(-7.1, -4.9)10.3-1.8(-3.2, -0.3)8.4-0.1(-1.3, 1.1)8.14.7(2.9, 6.6)9.18.9(5.1, 12.7)15.0 Pain-1.2(-1.4, -0.9)2.4-0.4(-0.8, 0.0)2.30.0(-0.2, 0.3)1.81.3(0.8, 1.7)2.22.0(1.2, 2.9)3.3 Physical Function-1.3(-1.6, -1.1)2.4-0.3(-0.6, 0.1)2.10.0(-0.3, 0.3)2.10.9(0.4, 1.4)2.41.8(0.8, 2.7)3.7 Fatigue-1.1(-1.4, -0.8)2.6-0.4(-0.7, 0.0)1.90.0(-0.3, 0.3)2.10.7(0.3, 1.1)2.11.3(0.5, 2.1)3.2 Stiffness-1.1(-1.4, -0.9)2.4-0.4(-0.7, 0.0)2.0-0.1(-0.4, 0.2)2.01.1(0.6, 1.5)2.21.8(1.0, 2.7)3.3 Participation-1.2(-1.5, -1.0)2.5-0.1(-0.5, 0.3)2.1-0.1(-0.4, 0.2)2.20.8(0.4, 1.3)2.22.0(1.1, 2.8)3.4Disease ActivityCDAI*-5.3(-6.3, -4.3)9.1-3.3(-5.4, -1.3)11.5-0.8(-2.0, 0.5)8.11.7(-0.1, 3.5)8.86.8(3.7, 9.8)12.0SDAI-5.6(-6.8, -4.4)9.2-3.5(-6.1, -0.9)12.2-1.9(-3.6, -0.2)8.91.5(-0.7, 3.7)9.24.7(1.0, 8.4)12.2DAS28-CRP-0.7(-0.8, -0.6)1.01-0.5(-0.7, -0.2)1.2-0.2(-0.4, 0.0)1.00.3(0.1, 0.5)1.00.5(0.2, 0.9)1.2Patient Global (0-10)-1.3(-1.5, -1.0)2.7-0.5(-0.9, -0.1)2.1-0.1(-0.4, 0.2)2.11.3(0.8, 1.8)2.42.9(2.1, 3.6)3.1MD Global (0-10)-1.2(-1.4, -1.0)1.9-0.7(-1.1, -0.3)-0.1-0.1(-0.4, 0.2)1.90.1(-0.3, 0.5)2.80.7(0.0, 1.5)2.8Swollen Joints (28)-1.4(-1.7, 1.0)3.2-1.0(-1.8, -0.2)4.6-0.4(-0.9, 0.0)3.00.0(-0.7, 0.7)3.41.3(0.2, 2.5)4.6Tender Joints (28)-1.5(-1.9, -1.1)3.9-1.3(-2.2, -0.3)5.50.0(-0.7, 0.6)4.30.3(-0.7, 1.2)4.52.2(0.8, 3.5)5.4Conclusion:In this large cohort of adults with ERA, the RA-FQ was responsive to change and generally distinguish between minimal and meaningful improvement and worsening. These data add to a growing evidence demonstrating robust psychometric properties of the RA-FQ and offer initial guidance about the amount of change associated with improvement or worsening, supporting its use in RA care, research and decision-making.Acknowledgements:The CATCH study was designed and implemented by the investigators and financially supported through unrestricted research grants from: Amgen and Pfizer Canada - Founding sponsors since January 2007; AbbVie Corporation and Hoffmann-LaRoche since 2011; Medexus Inc. since 2013;, Merck Canada since 2017, Sandoz Canada, Biopharmaceuticals since 2019,Gilead Sciences Canada since 2020 and Fresenius Kabi Canada Ltd. since 2021. Previously funded by Janssen Biotech from 2011-2016, UCB Canada and Bristol-Myers Squibb Canada from 2011-2018, Sanofi Genzyme from 2016-2017, and Eli Lilly Canada from 2016-2020.Disclosure of Interests:None declared

Background In younger individuals, low absolute risk of cardiovascular disease (CVD) may conceal an increased risk age and relative risk of CVD. Calculation of risk age is proposed as an adjuvant to absolute CVD risk estimation in European guidelines. We aimed to compare the discriminative ability of available risk age models in prediction of CVD in rheumatoid arthritis (RA). Secondly, we also evaluated the performance of risk age models in subgroups based on RA disease characteristics. Methods RA patients aged 30–70 years were included from an international consortium named A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Prior CVD and diabetes mellitus were exclusion criteria. The discriminatory ability of specific risk age models was evaluated using c-statistics and their standard errors after calculating time until fatal or non-fatal CVD or last follow-up. Results A total of 1974 patients were included in the main analyses, and 144 events were observed during follow-up, the median follow-up being 5.0 years. The risk age models gave highly correlated results, demonstrating R2 values ranging from 0.87 to 0.97. However, risk age estimations differed > 5 years in 15–32% of patients. C-statistics ranged 0.68–0.72 with standard errors of approximately 0.03. Despite certain RA characteristics being associated with low c-indices, standard errors were high. Restricting analysis to European RA patients yielded similar results. Conclusions The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. The influence of RA disease characteristics on the predictive ability of these prediction models remains inconclusive.

Aims Although immune-mediated inflammatory diseases (IMID) are associated with multiple mental health conditions, there is a paucity of literature assessing personality disorders (PDs) in these populations. We aimed to estimate and compare the incidence of any PD in IMID and matched cohorts over time, and identify sociodemographic characteristics associated with the incidence of PD. Methods We used population-based administrative data from Manitoba, Canada to identify persons with incident inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) using validated case definitions. Unaffected controls were matched 5:1 on sex, age and region of residence. PDs were identified using hospitalisation or physician claims. We used unadjusted and covariate-adjusted negative binomial regression to compare the incidence of PDs between the IMID and matched cohorts. Results We identified 19 572 incident cases of IMID (IBD n = 6,119, MS n = 3,514, RA n = 10 206) and 97 727 matches overall. After covariate adjustment, the IMID cohort had an increased incidence of PDs (incidence rate ratio [IRR] 1.72; 95%CI: 1.47–2.01) as compared to the matched cohort, which remained consistent over time. The incidence of PDs was similarly elevated in IBD (IRR 2.19; 95%CI: 1.69–2.84), MS (IRR 1.79; 95%CI: 1.29–2.50) and RA (IRR 1.61; 95%CI: 1.29–1.99). Lower socioeconomic status and urban residence were associated with an increased incidence of PDs, whereas mid to older adulthood (age 45–64) was associated with overall decreased incidence. In a restricted sample with 5 years of data before and after IMID diagnosis, the incidence of PDs was also elevated before IMID diagnosis among all IMID groups relative to matched controls. Conclusions IMID are associated with an increased incidence of PDs both before and after an IMID diagnosis. These results support the relevance of shared risk factors in the co-occurrence of PDs and IMID conditions.

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 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.

Objective.Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time.Methods.Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to ≤ 10; MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K.Results.There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years.Conclusion.Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

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)

Objective We determined the association between any common mental disorder (CMD: depression, anxiety disorder, bipolar disorder) and mortality and suicide in three immune-mediated inflammatory diseases (IMID), inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), versus age-, sex- and geographically-matched controls. Methods Using administrative data, we identified 28,384 IMID cases (IBD: 8695; MS: 5496; RA: 14,503) and 141,672 matched controls. We determined annual rates of mortality, suicide and suicide attempts. We evaluated the association of any CMD with all-cause mortality and suicide using multivariable Cox regression models. Results In the IMID cohort, any CMD was associated with increased mortality. We observed a greater than additive interaction between depression and IMID status (attributable proportion 5.2%), but a less than additive interaction with anxiety (attributable proportion −13%). Findings were similar for MS and RA. In IBD, a less than additive interaction existed with depression and anxiety on mortality risk. The IMID cohort with any CMD had an increased suicide risk versus the matched cohort without CMD. Conclusion CMD are associated with increased mortality and suicide risk in IMID. In MS and RA, the effects of depression on mortality risk are greater than associations of these IMID and depression alone.

Aims.After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population.Methods.Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year.Results.We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30–1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12–1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10–2.40).Conclusion.The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.

Background:RA is an inflammatory disease that results in pain and loss of function, especially in the hands and wrists. Brief self-assessment tools that can reliably and precisely quantify hand/wrist function are needed to assess inflammatory activity when a physical exam is not feasible and to capture day-to-day experience of living with RA. Neuro-QoL is part of the PROMIS family of self-report measures created using a patient-centred approach and IRT methodology. The Neuro-Qol Upper Extremity Function (UEF) scale measures ability across fine motor and ADLs involving digital, manual and reach-related function and self-care. Little is known about its performance in RA.Objectives:To evaluate the validity and responsiveness of the 8-item Neuro-QoL UEF in RA. We hypothesized scores would be strongly (r>.70) associated with MHAQ, MD-HAQ, and PROMIS PF, moderately (r=.4 to .7) to symptoms, disease activity, and QoL indicators, and be responsive to change in disease activity and PF.Methods:Data were from the 0 and 6-month visits of adults with early RA (sx Results:The 262 participants were mostly white (83%) women (71%) with a mean (SD) age of 55 (13). Summary statistics at 6-months are shown in Table 1. Neuro-QOL UEF was moderately-strongly correlated with MHAQ, MDHAQ, PROMIS-PF (|r|=.63-.75) and moderately correlated with pain and stiffness, (|r|=.59, -.64), and CDAI, SDAI, PT&MD Global, TJ & SJ (|r|=.39-.58). Neuro-QOL UEF was moderately correlated with PROMIS QoL domains Pain, Fatigue, Anxiety, Depression, Sleep & Participation (|r|=.39-.60).Table 1.Summary statistics of physical function and RA disease activity indices at 6 months.MeanSDMdn25%75%(Min, Max)Physical FunctionNeuro-Qol UEF46.59.753.837.553.8(21.8, 53.8)MHAQ (0-3)0.290.430.130.000.38(0.00, 2.25)MD-HAQ (0-10)1.391.640.700.002.00(0.00, 8.00)PROMIS-PF46.48.546.239.556.0(23.3, 56.0)RA Disease ActivityCDAI9.39.96.03.013.0(0.0, 56.0)SDAI10.710.96.83.115.2(0.0, 57.0)Patient Global3.02.5315(0, 10)MD Global1.82.2103(0, 9)Swollen Joints (28)2.13.7002(0, 20)Tender Joints (28)2.43.9103(0, 24)Neuro-QOL scores decreased in a dose-response manner across worsening CDAI DA states reflecting increasing impairment (Table 2). Persons with HDA reported the highest disability, scoring nearly 0.5 SD lower on the Neuro-QoL UEF than PROMIS PF. Change from baseline to 6 months in Neuro-QoL UEF was moderately correlated with changes in PROMIS PF, MHAQ, PT Global, and CDAI (|r|=.44-.65). The mean change and range from 0-6 months in Neuro-QoL was significantly larger than in PROMIS (8.9 [95% CI 7.5, 10.4] vs. 5.4 [95% CI 4.4, 6.4])(see Figure).Table 2.Mean scores (95% CI) at 6 months by CDAI level.REMLDAMDAHADNeuroQol UEF52.8 (51.8, 53.7)48.1 (46.6, 49.7)42.0 (39.4, 44.6)33.8 (30.5, 37.1)MHAQ (0-3)0.05 (0.02, 0.09)0.19 (0.14, 0.24)0.45 (0.34, 0.57)0.90 (0.63, 1.17)MD-HAQ (0-10)0.31 (0.17, 0.46)1.11 (0.90, 1.32)2.15 (1.71, 2.59)3.56 (2.56, 4.56)PROMIS-PF52.8 (51.4, 54.2)46.8 (45.3, 48.2)42.3 (40.4, 44.2)38.0 (34.4, 41.6)Conclusion:Clinicians, researchers, and patients benefit from practical self-report tools that reliably and precisely monitor hand function in RA. Results offer initial evidence of validity and responsiveness and support use of Neuro-QoL UEF to self-assess inflammatory activity in the hands and day-to-day experiences of living with RA.Acknowledgements:The CATCH study was designed and implemented by the investigators and financially supported through unrestricted research grants from: Amgen and Pfizer Canada - Founding sponsors since January 2007; AbbVie Corporation and Hoffmann-LaRoche since 2011; Medexus Inc. since 2013;, Merck Canada since 2017, Sandoz Canada, Biopharmaceuticals since 2019,Gilead Sciences Canada since 2020 and Fresenius Kabi Canada Ltd. since 2021. Previously funded by Janssen Biotech from 2011-2016, UCB Canada and Bristol-Myers Squibb Canada from 2011-2018, Sanofi Genzyme from 2016-2017, and Eli Lilly Canada from 2016-2020.Disclosure of Interests:None declared

Supplemental digital content is available in the text., Background Psychiatric comorbidities, such as depression and anxiety, are very common in persons with rheumatoid arthritis (RA) and can lead to adverse outcomes. By appropriately treating these comorbidities, disease-specific outcomes and quality of life may be improved. Objective The aim of this study was to systematically review the literature from controlled trials of treatments for depression and anxiety in persons with RA. Methods We searched multiple online databases from inception until March 25, 2015, without restrictions on language, date, or location of publication. We included controlled trials conducted in persons with RA and depression or anxiety. Two independent reviewers extracted information including trial and participant characteristics. The standardized mean differences (SMDs) of depression or anxiety scores at postassessment were pooled between treatment and comparison groups, stratified by active versus inactive comparators. Results From 1291 unique abstracts, we included 8 RA trials of depression interventions (6 pharmacological, 1 psychological, 1 both). Pharmacological interventions for depression with inactive comparators (n = 3 trials, 143 participants) did not reduce depressive symptoms (SMD, −0.21; 95% confidence interval [CI], −1.27 to 0.85), although interventions with active comparators (n = 3 trials, 190 participants) did improve depressive symptoms (SMD, −0.79; 95% CI, −1.34 to −0.25). The single psychological trial of depression treatment in RA did not improve depressive symptoms (SMD, −0.44; 95% CI, −0.96 to 0.08). Seven of the trials had an unclear risk of bias. Conclusions Few trials examining interventions for depression or anxiety in adults with RA exist, and the level of evidence is low to moderate because of the risk of bias and small number of trials.

Background:Several composite RA disease activity indices are commonly used in clinical practice and research. Different disease activity indices however can be inconsistent in classifying remission (REM).Objectives:1) Compare remission prevalence across 4 common RA indices; 2) compare changes in remission across indices; and, 3) Identify predictors of persistent active disease across all indices, in real-world early RA patients over 1 year follow up.Methods:Data were from patients with early RA (symptoms < 1 year) enrolled in the Canadian Early Arthritis Cohort (CATCH) between 2007 and 2018. Participants had active disease at enrolment, were treated with csDMARDs and completed standardized clinical assessments every 3-months. Remission status was assessed using 4 indices: 1) DAS28< 2.6 OR DAS28CRP < 2.5, 2) CDAI ≤ 2.8, 3) SDAI≤ 3.3, and 4) ACR/EULAR Boolean remission – SJC28, TJC28, CRP, PGA all ≦1. T-tests/ chi-squared tests were used to compare differences in remission prevalence by 1 year, and changes in remission before and after a QI program. Logistic regression was used to identify predictors of persistent active disease on all 4 indices.Results:1202 adults were eligible for this analysis. At enrolment, 877 (73%) were women, mean (sd) age was 55 (14), average disease activity was high (DAS28 5.1 (1.4); CDAI 27 (14); SDAI 29 (15)). Prevalence of remission by 12-months follow up was 14-21% higher when estimated with the DAS28 compared with CDAI, SDAI and Boolean criteria, and 378 (31%) did not achieve remission according to any of the 4 indices (Fig 1). Improvement in remission after a QI program however was similar across all 4 indices(~+15-17%). In adjusted logistic regression, Persistent active disease across all measures was most strongly associated with positive serostatus and smoking in men, and with obesity and more tender joints in women. Pain and lower education were predictors in BOTH men and women (Table 2)Table 1.Multivariable Logistic Regression Predicting Persistent Active Disease by 12-months across ALL RA indicesConclusion:In the absence of a single “best measure” that also takes in to account the patient’s perspective, we estimate unmet needs for achieving remission in the first year of follow up in 1 in 3 ERA patients who did not achieve remission by ANY of the 4 indices.References:[1] Kuriya B, Sun Y, Boire G, Haraoui B, etal. Remission in Early Rheumatoid Arthritis – A Comparison of New ACR/EULAR Remission Criteria to Established Criteria.J Rheumatol2012;39:1155-1158.Disclosure of Interests:Orit Schieir: None declared, Susan J. Bartlett Consultant of: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie, Speakers bureau: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie, Marie-France Valois: None declared, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Gilles Boire Grant/research support from: Merck Canada (Registry of biologices, Improvement of comorbidity surveillance)Amgen Canada (CATCH, clinical nurse)Abbvie (CATCH, clinical nurse)Pfizer (CATCH, Registry of biologics, Clinical nurse)Hoffman-LaRoche (CATCH)UCB Canada (CATCH, Clinical nurse)BMS (CATCH, Clinical nurse, Observational Study Protocol IM101664. SEROPOSITIVITY IN A LARGE CANADIAN OBSERVATIONAL COHORT)Janssen (CATCH)Celgene (Clinical nurse)Eli Lilly (Registry of biologics, Clinical nurse), Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Glen Hazlewood: None declared, Carol Hitchon Grant/research support from: UCB Canada; Pfizer Canada, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant of: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion,Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, LillyPharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Carter Thorne Consultant of: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Diane Tin: None declared, Vivian Bykerk: None declared

Background:RA patients with inadequate DMARD response may be treated with a TNF inhibitor (TNFi), non-TNFi or janus kinase inhibitor (JAKi) [1].Objectives:Compare characteristics of real-world early RA (ERA) patients starting TNFi, non-TNFi, and JAKi post DMARD failure.Methods:Data were analyzed from early RA patients (symptoms < 1 year) enrolled in CATCH who started TNFi, non-TNFi or JAKi as first line advanced therapy from 2014 to 2019. Descriptive statistics, t-tests and chi-square tests summarized and compared secular trends and patient characteristics initiating each class of therapy. Multinomial logistic regression analyses were done.Results:246 participants started advanced therapy during the study period; (75%) female, mean(SD) age 50(14) years. First line prescriptions for JAKi increased and TNFi decreased (Fig. 1). Those receiving JAKi had longer disease duration, fewer tender joints, and lower DAS28, CDAI, ESR, MD global (all p Table 1.Characteristics prior to starting advanced therapyVariableTotal Sample(N = 246)JAKi(N = 61)TNFi(N = 153)Non-TNFi(N = 32)p-value£Disease duration (months) mean (SD)39 (34.1)50.8 (39.3)32.5 (29.1)48 (38.6)0.0006DAS28 (ESR - CRP if ESR was missing) mean (SD)4.2 (1.4)3.6 (1.4)4.3 (1.4)4.8 (1.5)0.0012CDAI mean (SD)21.5 (14.8)16.5 (13.7)22.9 (14.8)24.8 (14.9)0.0089Tender joint count (0-28), median (IQR)§4 (7)2 (6)5 (8)6 (9)0.0224ESR median (IQR)§13 (20)12 (13)13 (20)28.0 (23.5)0.0448MD Global (0-10) mean (SD)4.2 (2.7)3.2 (2.7)4.4 (2.6)4.8 (2.8)0.0030§IQR: 75 – 25 percentile£p-value: ANOVA for continuous variable, chi-square for categoricalTable 2.Multinomial regression for initiating advanced DMARD therapyDisease stage & Clinical Disease ActivityAdvanced DMARDAdjusted for Age, sex, education, comorbidityFullyAdjustedφNon-TNF vs TNFJAK vsTNFNon-TNF vs TNFJAK vsTNFAge1.01 (0.98, 1.05)1.01 (0.99, 1.04)1.01 (0.97, 1.05)1.02 (0.99, 1.05)Women vs Men1.98 (0.71, 5.58)1.33 (0.63, 2.80)2.35 (0.76, 7.27)1.72 (0.73, 4.02)Education(< HS vs ≥ HS)2.92 (1.28, 6.63)1.49 (0.78, 2.86)2.83 (1.12, 7.15)2.08 (0.97, 4.47)RDCI baseline1.35 (1.01, 1.81)1.21 (0.95, 1.53)1.30 (0.95, 1.78)1.23 (0.94, 1.60)Private Insurance(No vs Yes)NINI1.26 (0.47, 3.40)0.99 (0.44, 2.25)RF PositiveNINI1.47 (0.56, 3.85)1.84 (0.82, 4.12)CDAININI1.01 (0.98, 1.04)0.97 (0.94, 1.00)RegionQuebec vs Ontario (ON)NINI0.59 (0.20, 1.72)0.44 (0.20, 0.94)West vs ONNINI1.32 (0.29, 5.98)0.11 (0.01, 0.99)φAdjusted for; baseline age, sex, education, RDCI; province; RF positive in first year; private insurance; CDAI at visit prior to initiationConclusion:Patient and physician related factors (location of practice) determined which advanced therapeutic was prescribed. JAKi use is increasing in ERA.Reference:[1]Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Annals of the Rheumatic Diseases Published Online First: 22 January 2020Disclosure of Interests:Madina Weiler: None declared, Orit Schieir: None declared, Marie-France Valois: None declared, Susan J. Bartlett Consultant of: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie, Speakers bureau: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Gilles Boire Grant/research support from: Merck Canada (Registry of biologices, Improvement of comorbidity surveillance)Amgen Canada (CATCH, clinical nurse)Abbvie (CATCH, clinical nurse)Pfizer (CATCH, Registry of biologics, Clinical nurse)Hoffman-LaRoche (CATCH)UCB Canada (CATCH, Clinical nurse)BMS (CATCH, Clinical nurse, Observational Study Protocol IM101664. SEROPOSITIVITY IN A LARGE CANADIAN OBSERVATIONAL COHORT)Janssen (CATCH)Celgene (Clinical nurse)Eli Lilly (Registry of biologics, Clinical nurse), Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Glen Hazlewood: None declared, Carol Hitchon Grant/research support from: UCB Canada; Pfizer Canada, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant of: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion,Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, LillyPharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Diane Tin: None declared, Carter Thorne Consultant of: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Vivian Bykerk: None declared, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB