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Objectives To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. Methods Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. Results In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: −0.04, 0.33) for 2 vs 0 visits; and +0.08 units (−0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. Conclusions In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.

A number of studies have demonstrated that patients with autoimmune disease have lower levels of vitamin D prompting speculation that vitamin D might suppress inflammation and immune responses in children with juvenile idiopathic arthritis (JIA). The objective of this study was to compare vitamin D levels in children with JIA at disease onset with healthy children. We hypothesized that children and adolescents with JIA have lower vitamin D levels than healthy children and adolescents. Data from a Canadian cohort of children with new-onset JIA (n= 164, data collection 2007-2012) were compared to Canadian Health Measures Survey (CHMS) data (n=4027, data collection 2007-2011). We compared 25-hydroxy vitamin D (25(OH)D) concentrations with measures of inflammation, vitamin D supplement use, milk intake, and season of birth. Mean 25(OH)D level was significantly higher in patients with JIA (79 ± 3.1 nmol/L) than in healthy controls (68 ± 1.8 nmol/L P.05). Patients with JIA more often used vitamin D containing supplements (50% vs. 7%; P.05). The prevalence of 25(OH)D deficiency (30 nmol/L) was 6% for both groups. Children with JIA with 25(OH)D deficiency or insufficiency (50 nmol/L) had higher C-reactive protein levels. Children with JIA were more often born in the fall and winter compared to healthy children. In contrast to earlier studies, we found vitamin D levels in Canadian children with JIA were higher compared to healthy children and associated with more frequent use of vitamin D supplements. Among children with JIA, low vitamin D levels were associated with indicators of greater inflammation.

The Rheumatoid Arthritis Flare Questionnaire (RA-FQ) is a patient-reported measure of disease activity in RA. We estimated minimal and meaningful change from the perspective of RA patients, physicians, and using a disease activity index.Data were from 3- to 6-month visits of adults with early RA enrolled in the Canadian Early Arthritis Cohort. Participants completed the RA-FQ, the Patient Global Assessment of RA, and the Patient Global Change Impression at consecutive visits. Rheumatologists recorded joint counts and MD Global. Clinical Disease Activity Index (CDAI) scores were computed. We compared mean RA-FQ change across categories using patients, physicians, and CDAI anchors.The 808 adults were mostly white (84%) women (71%) with a mean age of 55 and moderate-high disease activity (85%) at enrollment. At V2, 79% of patients classified their RA as changed; 59% were better and 20% were worse. Patients reporting they were a lot worse had a mean RA-FQ increase of 8.9 points, whereas those who were a lot better had a -6.0 decrease. Minimal worsening and improvement were associated with a mean 4.7 and - 1.8 change in RA-FQ, respectively, while patients rating their RA unchanged had stable scores. Physician and CDAI classified more patients as worse than patients, and minimal and meaningful RA-FQ thresholds differed by group.Thresholds to identify meaningful change vary by anchor used. These data offer new evidence demonstrating robust psychometric properties of the RA-FQ and offer guidance about improvement or worsening, supporting its use in RA care, research, and decision-making.

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

OBJECTIVE Undervaluing the effectiveness of conventional treatments may lead to overtreatment with biologic medications in children with juvenile idiopathic arthritis (JIA). Using data from a nationwide inception cohort and strict methods to control bias, the aim of our study was to estimate the real-world effectiveness of simple JIA treatment strategies recommended in current guidelines. METHODS Children with JIA who were recruited at 16 Canadian centers from 2005 to 2010 were followed for up to 5 years. For each child, all observed treatment changes over time were assessed by independent physicians using prospectively collected data and published response criteria. Success was defined as attainment of inactive disease or maintenance of this state when stepping down treatment; minimally active disease was deemed acceptable for children with polyarticular JIA. Success rates were calculated for treatments tried ≥25 times, and logistic regression analysis identified features associated with success. RESULTS A total of 4,429 treatment episodes were observed in 1,352 children. Nonsteroidal antiinflammatory drug (NSAID) monotherapy was attempted 697 times, mostly as initial treatment when

Objective The aim was to improve distressing patient-reported outcomes (PROs) that persisted in RA patients with clinically controlled inflammation (controlled RA). Methods In a pragmatic pilot study, we offered mindfulness-based stress reduction (MBSR), a group intervention, to controlled RA patients who had high (≥16) Centre for Evaluation Studies depression (CES-D) scores and/or patient general assessment of disease activity (PGA) at least 2/10 larger than evaluator general assessment (EGA) (PGA-EGA: Delta). Evaluations before, 6 and 12 months after MBSR included CES-D, PGA, modified HAQ, simple disease activity index (SDAI), anxiety (general anxiety disorder 7; GAD-7), coping strategies (coping with health injuries and problems; CHIP), sleep disturbance and pain. Facilitators and obstacles to recruitment and participation were identified. A subset of patients was interviewed for qualitative analysis of their experience. Results Out of 306 screened patients, 65 were referred, 39 (60%) agreed and 28 (43%) completed MBSR. Anticipated burden, timing and frequency of group meetings, commuting issues, age extremes and co-morbidities were barriers to participation. Up to 12 months after MBSR, anxiety, depression, emotion-oriented coping, sleep and function significantly improved. Nonetheless, no significant impact was observed on pain, PGA, Delta or SDAI. The interviews revealed that benefits, including integration of effective coping strategies, were maintained. Conclusion We addressed MBSR feasibility issues and selection of outcomes in controlled RA patients with distressing PROs. For patients who chose to participate in MBSR, lasting benefits were evident for anxiety, depression, sleep and function. Larger studies are required to evaluate the weaker impact of MBSR on RA-related pain and PGA.

OBJECTIVE Identification of the incidence of juvenile idiopathic arthritis (JIA)-associated uveitis and its risk factors is essential to optimize early detection. Data from the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort were used to estimate the annual incidence of new-onset uveitis following JIA diagnosis and to identify associated risk factors. METHODS Data were reported every 6 months for 2 years, then yearly to 5 years. Incidence was determined by Kaplan-Meier estimators with time of JIA diagnosis as the reference point. Univariate log-rank analysis identified risk factors and Cox regression determined independent predictors. RESULTS In total, 1,183 patients who enrolled within 6 months of JIA diagnosis met inclusion criteria, median age at diagnosis of 9.0 years (interquartile range [IQR] 3.8-12.9), median follow-up of 35.2 months (IQR 22.7-48.3). Of these patients, 87 developed uveitis after enrollment. The incidence of new-onset uveitis was 2.8% per year (95% confidence interval [95% CI] 2.0-3.5) in the first 5 years. The annual incidence decreased during follow-up but remained at 2.1% (95% CI 0-4.5) in the fifth year, although confidence intervals overlapped. Uveitis was associated with young age (

Objective To identify discrete clusters comprising clinical features and inflammatory biomarkers in children with JIA and to determine cluster alignment with JIA categories. Methods A Canadian prospective inception cohort comprising 150 children with JIA was evaluated at baseline (visit 1) and after six months (visit 2). Data included clinical manifestations and inflammation-related biomarkers. Probabilistic principal component analysis identified sets of composite variables, or principal components, from 191 original variables. To discern new clinical-biomarker clusters (clusters), Gaussian mixture models were fit to the data. Newly-defined clusters and JIA categories were compared. Agreement between the two was assessed using Kruskal–Wallis analyses and contingency plots. Results Three principal components recovered 35% (three clusters) and 40% (five clusters) of the variance in patient profiles in visits 1 and 2, respectively. None of the clusters aligned precisely with any of the seven JIA categories but rather spanned multiple categories. Results demonstrated that the newly defined clinical-biomarker lustres are more homogeneous than JIA categories. Conclusion Applying unsupervised data mining to clinical and inflammatory biomarker data discerns discrete clusters that intersect multiple JIA categories. Results suggest that certain groups of patients within different JIA categories are more aligned pathobiologically than their separate clinical categorizations suggest. Applying data mining analyses to complex datasets can generate insights into JIA pathogenesis and could contribute to biologically based refinements in JIA classification.

Fracture liaison services (FLS) have been shown to prevent efficiently subsequent fragility fractures (FF). However, very few studies have examined their implementation in depth. The purpose of this research was to identify factors influencing the implementation of a FLS at three sites in Quebec, Canada. From 2013 to 2015, individual and group interviews focused on experiences of FLS stakeholders, including implementation committee members, coordinators, and orthopaedic surgeons and their teams. Emerging key implementation factors were triangulated with the FLS patients' clinico-administrative data. The Consolidated Framework for Implementation Research guided the analysis of perceived factors influencing four intervention outputs: investigation of FF risk (using the FRAX score), communication with the participant primary care provider, initiation of anti-osteoporosis medications (when relevant), and referral to organized fall prevention activities (either governmental or community based). Among the 454 FLS patients recruited to the intervention group, 83% were investigated for FF risk, communication with the primary care provider was established for 98% of the participants, 54% initiated medication, and 35% were referred to organized fall prevention activities. Challenges related to restricted rights to prescribe medication and access to organized fall prevention activities were reported. FLS coordinator characteristics to overcome those challenges included self-efficacy beliefs, knowledge of community resources, and professional background. This study highlighted the importance of enabling access to services for subsequent FF prevention, consolidating the coordinator's role to facilitate a more integrated intervention, and involving local leaders to promote the successful implementation of the FLS.

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.

(Gilles Boire): It was both a pleasure and an honor to present the 2019 Dunlop-Dottridge Lecture. My co-author and I will now discuss benefits and pitfalls of biomarkers developed through emerging techniques, evaluated through the experiential perspective of a seasoned clinician, as they apply to the quest for biomarker identification in rheumatic diseases.

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.

Paget's disease of bone (PDB) is characterized by excessive and disorganized bone remodeling, in which bone-resorbing osteoclasts play a key role. We investigated microRNA (miR) expression in osteoclasts derived from the blood of 40 PDB patients and 30 healthy controls. By deep sequencing, a preliminary analysis identified differentially expressed miRs in a discovery cohort of 9 PDB patients and 9 age and sex-matched healthy controls. Six mature miRs, miR-29b1-3p, miR-15b-5p, miR-181a-5p, let-7i-3p, miR-500b-5p, and miR-1246, were found to be significantly decreased in pagetic overactive osteoclasts. The differential expression of the miRs was confirmed by the analysis of a larger independent cohort using qPCR. In an integrative network biology analysis of the miR candidates, we identified strong validated interactions between the miRs and some pathways, primarily apoptosis, and major osteoclast signaling pathways including PI3K/Akt, IFNγ, or TGFβ, as well as c-Fos, a transcription factor, and MMP-9, a metalloprotease. In addition, other genes like CCND2, CCND1, WEE1, SAMHD1, and AXIN2 were revealed in this network of interactions. Our results enhance the understanding of osteoclast biology in PDB; our work may also provide fresh perspectives on the research or therapeutic development of other bone diseases. KEY MESSAGES: miR profile in overactive osteoclasts from patients with Paget's disease of bone. Six mature miRs were significantly decreased in pagetic osteoclasts vs controls. miRs of interest: let7i-3p, miR-15b-5p, -29b1-3p, -181a-5p, -500b-5p, and -1246. Target genes and enriched pathways highlight the importance of apoptotic pathways.

OBJECTIVE To describe patterns of glucocorticoid use in a large real-world cohort with early rheumatoid arthritis (RA) and assess the impact on disease activity and treatment. METHODS Data are from adults with new RA (≤1 year) recruited to the Canadian Early Arthritis Cohort (CATCH) and are stratified on the basis of whether a person was prescribed oral glucocorticoids within 3 months of study entry. Disease activity was compared over 24 months. Mixed-effects logistic regression was used for adjusted odds ratios (aORs) of escalation to biologics separately for 12 and 24 months, with random effects terms to account for prescribing patterns clustering by study site. RESULTS Among 1891 persons, 30% received oral steroids. Users were older, were less often employed, and had shorter disease duration and higher disease activity. Disease activity improved over time, with early glucocorticoid users starting at higher levels of disease activity. Participants with early oral glucocorticoids were more likely to be on a biologic at 12 months (aOR = 2.4; 95% confidence interval [CI], 1.5-3.7) and 24 months (aOR = 1.9; 95% CI, 1.3-3.0). Despite Canadian clinical practice guidelines to limit corticosteroid use to short-term or 'bridge' therapy, 30% of patients who used oral glucocorticoids still used them 2 years later. CONCLUSION Early steroids were prescribed sparingly in CATCH and were often indicative of more active baseline disease as well as the need for progression to biologics.

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).

Objective.Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA–related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis.Methods.Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population.Results.The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: P = 0.011 and r2 = 0.175 for GRWS; P = 0.008 and r2 = 0.178 for GRSCS; P = 0.002 and r2 = 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: P = 0.049 and r2 = 0.176 for GRCS; P = 0.022 and r2 = 0.176 for GRWS; P = 0.022 and r2 = 0.176 for GRSCS; P = 0.011 and r2 = 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis).Conclusion.Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.

ObjectivesThis study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity.MethodsPlasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits.ResultsAt enrollment, sLRP1 levels correlated negatively with age and active joint counts. Children showed significantly higher levels of sLRP1 than adolescents (mean ranks: 55.4 and 41.9, respectively; P = 0.02). Participants with 4 or fewer active joints, compared to those with 5 or more active joints, had significantly higher sLRP1 levels (mean ranks: 56.2 and 40.7, respectively; P = 0.006). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r = –0.235, P = 0.017). In the entire cohort, sLRP1 levels at enrollment and 6 months later correlated with 13 and 6 pro- and antiinflammatory biomarkers, respectively. In JIA categories, sLRP1 correlations with inflammatory markers were significant in rheumatoid factor–negative polyarticular JIA, oligoarticular JIA, enthesitis-related arthritis, and psoriatic arthritis at enrollment. Higher sLRP1 levels at enrollment increased the likelihood of absence of active joints 6 months later.ConclusionPlasma sLRP1 levels correlate with clinical and biomarker indicators of short-term improvement in JIA disease activity, supporting sLRP1 as an upstream biomarker of potential utility for assessing JIA disease activity and outcome prediction.

Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.Methods.Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).Results.A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. Failure of adherence to T2T-LDA was noted in 1765 visits (40.5%). In the baseline multivariable model, a high number of comorbidities (OR 1.10, 95% CI 1.02–1.19), smoking (OR 1.32, 95% CI 1.08–1.63) and high number of tender joints (OR 1.03, 95% CI 1.02–1.04) were independently associated with failure to implement T2T, while anticitrullinated protein antibody/rheumatoid factor positivity (OR 0.63, 95% CI 0.50–0.80) was a significant facilitator of T2T. Results were similar in the longitudinal model.Conclusion.Lack of adherence to T2T in the RA BIODAM cohort was evident in a substantial proportion despite being a protocol requirement, and this could be predicted by clinical features. [Rheumatoid Arthritis (RA) BIODAM cohort; ClinicalTrials.gov: NCT01476956].

Objective To identify early predictors of disease activity at 18 months in JIA using clinical and biomarker profiling. Methods Clinical and biomarker data were collected at JIA diagnosis in a prospective longitudinal inception cohort of 82 children with non-systemic JIA, and their ability to predict an active joint count of 0, a physician global assessment of disease activity of ≤1 cm, and inactive disease by Wallace 2004 criteria 18 months later was assessed. Correlation-based feature selection and ReliefF were used to shortlist predictors and random forest models were trained to predict outcomes. Results From the original 112 features, 13 effectively predicted 18-month outcomes. They included age, number of active/effused joints, wrist, ankle and/or knee involvement, ESR, ANA positivity and plasma levels of five inflammatory biomarkers (IL-10, IL-17, IL-12p70, soluble low-density lipoprotein receptor-related protein 1 and vitamin D), at enrolment. The clinical plus biomarker panel predicted active joint count = 0, physician global assessment ≤ 1, and inactive disease after 18 months with 0.79, 0.80 and 0.83 accuracy and 0.84, 0.83, 0.88 area under the curve, respectively. Using clinical features alone resulted in 0.75, 0.72 and 0.80 accuracy, and area under the curve values of 0.81, 0.78 and 0.83, respectively. Conclusion A panel of five plasma biomarkers combined with clinical features at the time of diagnosis more accurately predicted short-term disease activity in JIA than clinical characteristics alone. If validated in external cohorts, such a panel may guide more rationally conceived, biologically based, personalized treatment strategies in early JIA.

ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 ResultsIn total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52).ConclusionIn daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.

Objective Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction. Methods The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score ≥ 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via videoconference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention. Ethics and dissemination The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak., Highlights • No RCTs have tested mental health interventions in contagious disease outbreaks. • People with scleroderma face fear and isolation during COVID-19. • SPIN-CHAT is designed to improve mental health in SSc patients during COVID-19. • SPIN-CHAT provides 12 group sessions over 4 weeks. • The SPIN-CHAT trial will randomize 162 participants to intervention or waitlist.

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)

To assess adherence to 3 system-level performance measures in a national early rheumatoid arthritis (RA) cohort.Patients enrolled in the Canadian Early Arthritis Cohort (2007-2015) who met 1987 or 2010 American College of Rheumatology/European League Against Rheumatism criteria with1 year of symptom duration and ≥1 year of followup after enrollment were included. Performance measures assessed were the percentage of RA patients seen in yearly followup, and the number of gaps between visits of12 or14 months, the percentage of RA patients treated with a disease-modifying antirheumatic drug (DMARD), and days from RA diagnosis to initiation of a DMARD. Results are shown stratified by enrollment year to assess for temporal changes in performance.A total of 1,763 early RA patients were included (mean age 54 years, 73% female, and 82% white). At enrollment, mean ± SD disease duration was 6 ± 3 months, and Disease Activity Score in 28 joints was 5.1 ± 1.5. Over 8 years, the proportion of patients seen in annual followup declined from 100% to 91%. Over followup, 42% of patients had 0 gaps in care of12 months, and 64% had 0 gaps14 months. The percentage of DMARD-treated early RA patients was and remained high (95-87%), and the percentage receiving DMARDs within 14 days of diagnosis was 75%. Median time-to-DMARD therapy was 1 day, indicating DMARDs were initiated at diagnosis (90th percentile 93 days).There was evidence of high adherence to system-level performance measures in this early RA cohort following a protocol. Small declines in performance were noted with increasing length of patient followup. Our findings are useful for performance measure benchmarking.

Interventions targeting patients with recent fragility fracture and their physician were most successful at initiating osteoporosis treatment during the first 12 months. This window of opportunity had already closed after 1 year. The reasons for declining or accepting the intensive intervention were explored in patients still untreated at 12 months. A fragility fracture (FF) event identifies patients most likely to benefit from osteoporosis treatment. Nonetheless, most FF patients go untreated. Our objective was to determine how long an incident FF remains a strong incentive to initiate osteoporosis treatment. A total of 1086 men and women over age 50 with a recent FF event were assigned to either standard care (SC), to minimal (MIN), or intensive (INT) interventions targeting patients and their family physician to initiate osteoporosis treatment. Inpatients with FF (mainly hip) evaluated by rheumatologists were also included in a specialized group (SPE; n = 324). At 1 year, untreated patients in both the SC and the MIN groups were offered an INT intervention. The cohort was followed through 48 months. A qualitative analysis of patient-centered decision-making associated with initiation of treatment was conducted. In MIN and INT groups, osteoporosis treatment was initiated in 41.0 and 54.3% of untreated patients by 12 months, respectively, compared to 68.4% in SPE and 18.9% in SC groups; initiation rates drastically dropped thereafter. Over 4863 patient-years of follow-up, the rates of new FF were 3.4 per 100 patient-years, without significant differences between patients with initial major or minor FF, nor between control or intervention groups. Failure by patients and physicians to recognize FF as a sign of underlying bone disease contributed the most to lack of treatment. While incident FFs are an ideal opportunity for starting osteoporosis treatment, 1 year later, the therapeutic window of opportunity has already closed.

While fragility fractures (FFs) are one of the strongest predictors of subsequent osteoporotic fractures, it remains unclear whether low-trauma ankle fractures have this ability. The aim of the study was to identify the characteristics of patients with low-trauma ankle FFs who develop subsequent FFs. The OPTIMUS initiative is a strategy to improve osteoporosis treatment post-FF in orthopedic clinics. FRAX scores without BMD (FRAX-BMI) were calculated at time of inclusion. Recurrent FFs were recorded over a 48-month follow-up. All FFs were X-ray-confirmed. A total of 265 patients with initial ankle FF were included (190 women; mean age 62.8 ± 9.6 years), of whom 15 developed new FFs. Patients with ankle FFs had longer time until recurrence and lower 2-year incidence of recurrent FFs (3.2%) compared with those having wrist FFs (9.0%) or other initial FFs (9.6%), and 4-year incidence rates of 6.2, 13.4, and 15.3%, respectively (log-rank test, p = 0.001). With an ankle FF at inclusion, recurrent FFs were more frequent in patients with previous FF (6.2 per 100 patient-years; p

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

We studied children enrolled within 90 days of juvenile idiopathic arthritis diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) prospective inception cohort to identify longitudinal trajectories of pain severity and features that may predict pain trajectory at diagnosis. A total of 1062 participants were followed a median of 24.3 months (interquartile range = 16.0-37.1 months). Latent trajectory analysis of pain severity, measured in a 100-mm visual analogue scale, identified 5 distinct trajectories: (1) mild-decreasing pain (56.2% of the cohort); (2) moderate-decreasing pain (28.6%); (3) chronically moderate pain (7.4%); (4) minimal pain (4.0%); and (5) mild-increasing pain (3.7%). Mean disability and quality of life scores roughly paralleled the pain severity trajectories. At baseline, children with chronically moderate pain, compared to those with moderate-decreasing pain, were older (mean 10.0 vs 8.5 years, P = 0.01) and had higher active joint counts (mean 10.0 vs 7.2 joints, P = 0.06). Children with mild-increasing pain had lower joint counts than children with mild-decreasing pain (2.3 vs 5.2 joints, P < 0.001). Although most children with juvenile idiopathic arthritis in this cohort had mild or moderate initial levels of pain that decreased quickly, about 1 in 10 children had concerning pain trajectories (chronically moderate pain and mild-increasing pain). Systematic periodic assessment of pain severity in the months after diagnosis may help identify these concerning pain trajectories early and lay out appropriate pain management plans. Focused research into the factors leading to these concerning trajectories may help prevent them.

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

Background:Early diagnosis and rapid initiation of DMARDs following a treat-to-target approach have made remission a realizable goal for many with RA. Yet, some patients are unable to sustain remission over time.Objectives:To describe longitudinal patterns of remission and identify predictors of sustained vs transient remission in real-world early RA patients.Methods:Data were from the Canadian Early Arthritis Cohort (CATCH), a prospective study of early RA patients (symptoms < 1 year) treated in rheumatology clinics across Canada from 2007- 2019. The sample was limited to patients with active disease at enrolment who later reached remission (SDAIResults:The study included 1,419 (46%) CATCH participants that reached remission. At enrolment, most (70%) were female, mean(sd) SDAI was high (27(15)) and 92% were treated with csDMARDs. Only 47% remained in sustained remission by 12-months and, only 40% by 24 months (Pattern 1) (Figure). Among patients with transient remission patterns, transitions to LDA only (Pattern 2) were more common than to MDA/HDA over FU (Pattern 3) (Fig 1). Older age, female sex, smoking, higher comorbidity index and positive serology, were significantly associated with transient remission patterns (Table). There were also borderline significant associations between transient remission patterns and longer time to remission, lack of early MTX treatment and reducing treatment after remission (Table).Table .Adjusted Multinomial Regression Results of Predictors of Transient Remission Patterns over 24-Month Follow UpPattern 2 vs, Pattern 1OR (95% CI)Pattern 3 vs. Pattern 1OR (95% CI)Age1.01 (1.00, 1.02)1.01 (0.99, 1.02)Women vs Men1.78 (1.33, 2.39)1.63 (1.09, 2.44)Current smoker1.57 (1.09, 2.28)1.53 (0.95, 2.47)RDCI at baseline1.11 (0.99, 1.25)1.30 (1.13, 1.50)Seropositive1.38 (1.03, 1.85)1.21 (0.81, 1.80)MTX first 3 months1.18 (0.85, 1.63)0.76 (0.51, 1.12)Time to remission (months)1.01 (1.00, 1.01)1.01 (1.00, 1.02)Treatment reduction after REM vs. No Change1.33 (0.96, 1.86)1.01 (0.99, 1.02) Pattern 1: Sustained REM Pattern 2: Transient REM: Transitions to LDA only Pattern 3: Transient REM: Transitions to MDA/HDA RDCI: Rheumatic Disease Comorbidity Index (range 0-9) Treatment reduction: Change from biologic or JAK to csDMARD(s) OR reduction in number of csDMARDs OR change from MTX +/- csDMARDs to non-MTX csDMARDFigure.Distribution of Disease Activity States over 12-24 After First Achieving SDAI REMConclusion:Results of this large longitudinal analysis of real-world data suggests that < 50% of patients that reach remission sustain remission for 12-24months. Closer monitoring of patients with prognostic indicators for transient remission and additional research focusing on why remission is lost may help improve the rates of sustained remission.References:[1]Ajeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017;9(10):249-62.Disclosure of Interests:Orit Schieir: None declared, Glen Hazlewood: 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, 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, Lilly Pharmaceuticals, 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 : Despite their efficacy at controlling joint inflammation, current treatments of rheumatoid arthritis (RA) leave up to 40% of patients into non-remission. Non-remission, frequently due to persistently negative self-reported impact of RA, was found to be associated with significant persistent depressive symptoms 6-7 months after initiation of arthritis treatment. Mindfulness-Based Stress Reduction (MBSR) is proposed to improve depressive symptoms and RA-related clinical outcomes. To pave the way for an eventual randomized controlled trial, a feasibility and acceptability study of MBSR has been realized. Methods: A standardized 8-week MBSR program was offered to groups of patients with controlled inflammatory disease but high levels of depressive symptoms.Qualitative interviews based on a theoretical framework of acceptability were conducted. Change in depressive symptoms (CES-D tool), fatigue and pain (SF-36), anxiety (GAD-7), pain, disease activity (PtVAS and SDAI scores) was measured over a 6-month period. Results: 27 patients have been recruited (3 distinct MBSR groups). Factors leading to a higher rate of success in recruitment were identified. Despite the small sample, the intervention was found to have a clear impact on depressive symptoms (p=0.004), anxiety (p=0.005), and social functioning (from the SF-36; p=0.04). Patients reported that MBSR gave them the opportunity to control their reactions in face of stressful situations.Perceptions were almost uniformly positive towards MBSR, and most appear to have integrated some part of the intervention in their daily life. Conclusions: Although recruitment was challenging, a MBSR trial on depressed patients with controlled inflammatory disease was found acceptable and feasible within this population. Preliminary clinical results showed positive impacts of such intervention.

Current guidelines recommend treating patients with rheumatoid arthritis (RA) by targeting remission, or if that fails, low disease activity, providing explicit directives for pharmacological interventions when arthritis remains active1. Similar recommendations are being proposed for psoriatic arthritis2. Definitions of disease activity in immune-mediated inflammatory arthritides (e.g., Simple Disease Activity Index in RA) incorporate objective [e.g., C-reactive protein (CRP) levels] and physician-derived measures of inflammation [e.g., swollen joint counts (SJC), physician’s global assessment of disease activity (PGA)] along with patient-derived ones [e.g., tender joint counts, patient’s global assessment of disease activity (PtGA)]3. Because of ever-increasing numbers and better use of effective biologic and nonbiologic antirheumatic drugs (DMARD), remission should represent a reasonable goal for every patient with chronic inflammatory arthritis. Unfortunately, control of inflammation does not directly translate into remission. Rheumatologists confidently use their PGA (and SJC) as their gold standard for treatment decisions regarding DMARD4, but remain puzzled when the inflammation is well controlled, but the patient still feels ill5. Persistent pain, fatigue, functional limitations, and psychological factors all contribute to elevated PtGA values in patients with controlled inflammation6. Ferreira, et al recently described this disconnect as 2 complementary domains needing distinct approaches: (1) control of inflammation, reflected by CRP and SJC, using DMARD; and (2) effect of disease indicated by elevated PtGA values, using adjunctive therapies yet to be defined6. There are biological, behavioral, and psychological reasons for the connection between inflammatory arthritis and affective disorders. Elevated levels of proinflammatory cytokines (e.g., interleukin 6 and tumor necrosis factor-α) limit psychological adaptation to disease, and when … Address correspondence to Dr. G. Boire, Department of Medicine, CIUSSS de l’Estrie - CHUS, 3001 12th Ave. North, Division of Rheumatology, Room 3853, Sherbrooke, Quebec J1H 5N4, Canada. E-mail: gilles.boire{at}usherbrooke.ca

Accurate diagnosis of inflammatory arthritides remains a challenge because of substantial clinical overlap. To achieve a granular classification for informing clinical decisions, numerous potential serologic biomarkers have been identified. Rheumatologists have settled on rheumatoid factor and anti-citrullinated protein antibodies for the diagnosis of rheumatoid arthritis (RA) based on specificity and sensitivity and their ability to be integrated into clinical algorithms. These biomarkers should be interpreted in their specific clinical context. This article discusses the serologic basis for the diagnosis of RA, how these biomarkers have framed conceptualization of the pathogenesis of RA, and the inherent limitations in their use.

Background The frequency and characteristics of patients with Palindromic Rheumatism (PR) (transient acute attacks of articular inflammation) prior to early rheumatoid arthritis (ERA) are unknown. Objectives To compare ERA patients who did versus did not report a history of transient episodes of joint inflammation preceding RA diagnosis. Methods Study participants were patients with ERA or suspected RA (symptoms Results 154 ERA patients were included; 66% were female and mean (sd) age was 54 (15) years. 54% had previous joint pain and swelling prior to their current episode; 42% endorsed prior episodic joint pain and swelling, approximately half of whom (20% of total, N=31) reported transient joint symptoms for over six months. Patients reporting previous palindromic symptoms were more often female, seropositive, had more comorbidities, and lower swollen joints and baseline CDAI (p Conclusion Half of ERA patients self-reported transient episodes of inflammatory arthritis prior to being diagnosed with RA. They are more likely female, seropositive, with higher income and lower disease activity. Acknowledgement 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 since 2011; Medexus Inc. since 2013; Eli Lilly Canada since 2016 and Merck Canada since 2017. Previously funded by Hoffmann-LaRoche and Janssen Biotech from 2011-2016,UCB Canada and Bristol-Myers Squibb Canada from 2011-2018, and Sanofi Genzyme from 2016-2017. Disclosure of Interests Leah Ellingwood: None declared, Orit Schieir: None declared, Marie-France Valois: None declared, Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Carol Hitchon: None declared, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Glen Hazlewood: None declared, 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 for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, 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 Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Janet Pope Consultant for: Eli Lilly and Company

Background Rheumatoid arthritis (RA) treatment emphasizes aggressive titration of disease-modifying antirheumatic drugs (DMARDs) with the goal of achieving disease remission. This often includes the use of multiple DMARDs in combination, which can have a significant impact on patients’ lives and add costs to the healthcare system. Objectives To describe the patterns of sustained remission and subsequent treatment reduction in usual clinical practice for patients with early RA. Methods Patients (age >18) enrolled in the Canadian early ArThritis CoHort (CATCH) between January 2007 to March 2017 were analyzed. CATCH is a prospective, observational study of patients with early inflammatory arthritis (symptoms 2.6) and those treated with at least one DMARD or biologic agent within the first three months of study enrolment. We defined sustained remission as achieving a DAS28 Results Eight hundred and thirty-seven (40%) of the 2,097 eligible patients achieved sustained remission during the study period. Of these, 60% did so within the first 18 months and 92% within the first four years (Figure 1). The mean (SD) baseline DAS28 was 5.1 (1.3), and HAQ-DI was 1.0 (0.7). At the time of remission, 80% were prescribed methotrexate (55% subcutaneously), 71% were prescribed combination therapy with other conventional synthetic DMARDs, and 13% were prescribed a biologic agent. In the year after attaining sustained remission, 327 (39%) patients reduced treatment in the following pattern (patients may have had more than one change): 250 patients (30%) reduced or stopped methotrexate, 196 patients (23%) reduced or stopped non-methotrexate DMARDs, and 34 patients (4%) reduced or stopped biologic agents. Of those that reduced or stopped a biologic, only one was due to side effects. For the 250 patients who reduced or stopped methotrexate, 25 were for a side effect. Conclusion Achieving sustained remission occurred in 40% of early RA patients in usual clinical practice. Treatment reductions following sustained remission occurred in over a third of patients over the next 12 months, and consisted mainly of adjustment in non-biologic DMARDs. Disclosure of Interests Maria Powell: None declared, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Orit Schieir: None declared, Janet Pope Consultant for: Eli Lilly and Company, Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, CArol Hitchon Grant/research support from: Pfizer, UCB (unrelated studies), 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 for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, 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, Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Diane Tin: None declared, Marie-France Valois: None declared, Glen Hazlewood : None declared

Background Fatigue is common in early RA(ERA) and though some patients experience improvement in fatigue when disease is well controlled, others experience persistent fatigue associated with work disability, poor QOL, and depression. Objectives To compare patterns and predictors of improved vs. persistent fatigue in the first year of ERA. Methods Data were from ERA patients (symptoms Results The 1002 pts were mostly white (81%), female (71%), with a mean (SD) age of 54 (15); 32% were obese. 70% had high fatigue at baseline; these patients were more obese, had OA/backpain, poor sleep, depression, major stress, and higher disease activity (Table 1). Among those with initial high fatigue, 30% had persistent fatigue at 12 months and was associated with obesity, comorbidities, FM, longer symptom duration, and slightly lower baseline fatigue. Predictors of improved fatigue in multivariable models were BMI Conclusion Fatigue is common in ERA and associated with active disease, worse pain and disability, obesity, depression, major stressors, poor sleep and OA/backpain. In high fatigue pts, those who are not obese, have higher pain, and take ≥20 mg MTX are more likely to improve over the first year. Optimizing weight, sleep, physical and emotional health and MTX use may improve persistent fatigue beyond control of RA inflammation. Disclosure of Interests Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Orit Schieir: None declared, Marie-France Valois: None declared, CArol Hitchon Grant/research support from: Pfizer, UCB (unrelated studies), Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Glen Hazlewood: None declared, Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Janet Pope Consultant for: Eli Lilly and Company, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Diane Tin: None declared, 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 for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, 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, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron