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This study was undertaken to assess the effects of a web-based program, MyLupusGuide, developed to facilitate self-management in systemic lupus erythematosus (SLE).In this randomized controlled online study, participants received either immediate access to the MyLupusGuide site or delayed access starting on month 3. The primary outcome was the patient activation measure (PAM) score. Secondary outcomes included measurements of health status, self-efficacy, coping, perceived patient-physician relationship, and medication adherence. Outcomes were measured at the baseline visit and at the 3-month and 6-month follow-up visits. We used linear mixed modeling to compare PAM scores between the 2 groups at months 3 and 6.There were 541 participants included in this study. The mean ± SE age was 50 ± 14 years; 93% were female and 74% were White. The mean ± SE disease duration was 17 ± 12 years, and 56% visited MyLupusGuide at least once. The baseline mean ± SE PAM score was 61.2 ± 13, with 36% scoring low for perceived self-management skills. After 3 months of exposure to MyLupusGuide, there were no differences in terms of PAM scores between groups. In exploratory analyses, we found significant improvement in PAM scores in those who had low PAM scores at baseline and in male individuals. We observed significant improvements in self-efficacy before and after access to MyLupusGuide and delayed improvements at month 6 compared to month 3 in terms of mental health and emotional coping.MyLupusGuide increases self-efficacy but not patient activation. A total of 56% of participants visited the MyLupusGuide site during the study period. Individuals with lupus need support to become activated toward self-management behaviors.

Reports of mortality risks among individuals with giant cell arteritis (GCA) have been mixed. Our aim was to evaluate all-cause mortality among individuals with GCA relative to the general population over time.We performed a population-based study in Ontario, Canada using health administrative data. We studied a cohort of 22,677 GCA patients ages ≥50 years that was identified using a validated case definition (with 81% positive predictive value, 100% specificity). General population comparators were residents ages ≥50 years without GCA. Deaths were ascertained from vital statistics. Annual crude, age- and sex-standardized, and age- and sex-specific all-cause mortality rates were determined for individuals with and without GCA between 2000 and 2018. Standardized mortality ratios (SMRs) were estimated.Age- and sex-standardized mortality rates were significantly higher for GCA patients than comparators, and trending to increase over time with 50.0 deaths per 1,000 GCA patients in 2000 (95% confidence interval [95% CI] 34.0-71.1) and 57.6 deaths per 1,000 GCA patients in 2018 (95% CI 50.8-65.2), whereas mortality rates in the general population significantly declined over time. The annual SMRs for GCA patients generally increased over time, with the lowest SMR occurring in 2002 (1.22 [95% CI 1.03-1.40]) and the highest in 2018 (1.92 [95% CI 1.81-2.03]). GCA mortality rates were more elevated for male patients than female patients.Over a 19-year period, mortality rates were increased among GCA patients relative to the general population, and more premature deaths were occurring in younger age groups. The relative excess mortality for GCA patients did not improve over time.

Background Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. We completed an initial feasibility trial of an online self-administered version of the Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program using the cohort multiple randomized controlled trial (RCT) design. Due to low intervention offer uptake, we will conduct a new feasibility trial with progression to full-scale trial, using a two-arm parallel, partially nested RCT design. The SPIN-SELF Program has also been revised to include facilitator-led videoconference group sessions in addition to online material. We will test the group-based intervention delivery format, then evaluate the effect of the SPIN-SELF Program on disease management self-efficacy (primary) and patient activation, social appearance anxiety, and functional health outcomes (secondary). Methods This study is a feasibility trial with progression to full-scale RCT, pending meeting pre-defined criteria, of the SPIN-SELF Program. Participants will be recruited from the ongoing SPIN Cohort (http://www.spinsclero.com/en/cohort) and via social media and partner patient organizations. Eligible participants must have SSc and low to moderate disease management self-efficacy (Self-Efficacy for Managing Chronic Disease (SEMCD) Scale score ≤ 7.0). Participants will be randomized (1:1 allocation) to the group-based SPIN-SELF Program or usual care for 3 months. The primary outcome in the full-scale trial will be disease management self-efficacy based on SEMCD Scale scores at 3 months post-randomization. Secondary outcomes include SEMCD scores 6 months post-randomization plus patient activation, social appearance anxiety, and functional health outcomes at 3 and 6 months post-randomization. We will include 40 participants to assess feasibility. At the end of the feasibility portion, stoppage criteria will be used to determine if the trial procedures or SPIN-SELF Program need important modifications, thereby requiring a re-set for the full-scale trial. Otherwise, the full-scale RCT will proceed, and outcome data from the feasibility portion will be utilized in the full-scale trial. In the full-scale RCT, 524 participants will be recruited. Discussion The SPIN-SELF Program may improve disease management self-efficacy, patient activation, social appearance anxiety, and functional health outcomes in people with SSc. SPIN works with partner patient organizations around the world to disseminate its programs free-of-charge. Trial registration ClinicalTrials.govNCT04246528. Registered on 27 January 2020

Children and adults may develop Behçet's disease (BD), often with ocular involvement such as uveitis. This study aimed to determine the prevalence and type of ocular manifestations in childhood and adult BD.Medline, Web of Science and Cochrane databases were searched from inception to October 5, 2018 to identify publications related to Behçet's disease comprising minimum twenty patients and providing the frequency of ocular manifestations (OC). Random effects models were used to combine the prevalence of OC in adults and children with BD. Heterogeneity was evaluated using I2.The search resulted in 3129 articles, of which 51 were included in meta-analysis. OCs were slightly more frequent in childhood onset BD with the mean [95% Confidence Interval] frequency of 45 [34-56%] compared to 36 [29-43%] in adults, however, this difference was not statistically significant (p=0.198). In both children and adults, posterior uveitis (children 27% vs. adults 25%, and retinal vasculitis in adults 16%) was the most common ocular manifestation, followed by anterior uveitis (children 18% vs. adults 23%). When comparing the distribution of OC in Behcet's in adults, there was geographic variation where OC were higher in Turkey and the Middle East 42%, followed by Europe and North America (36%), North Africa 26% and East Asia 25% but not significantly (p=0.27).Ocular manifestations, predominantly uveitis; are common in BD. Ocular manifestations are not proportionately more frequent in adults with BD along the ancient Silk Road.

Objective To evaluate the nature and burden of residual disease in rheumatoid arthritis (RA) in patients who meet treatment targets. Second, for those who did not meet targets, to evaluate how much is due to patient symptoms. Methods Prospective and retrospective studies were searched in Medline, Embase, and Cochrane Library in the English language from January 1, 2008 to April 18, 2018; conference abstracts (from January 2016 to April 2018) and reference lists of relevant studies were also screened. Results Of 8,339 records identified, 55 were included in the review; 53 were unique studies, including 10 randomized controlled trials. Of these, 48 reported on patients who achieved low disease activity (LDA) or remission. Studies varied in population, treatment goals, and outcome reporting. The proportions of patients with residual symptoms in these studies varied by the definitions used for LDA or remission and were more often reported in patients with LDA than those in remission. The most commonly reported outcome measures were functional disability (n = 34 studies), tender or swollen joints (n = 18), pain (n = 17), patient global assessment (n = 15), and fatigue (n = 14). However, few studies reported the percentage of patients achieving a specific threshold, which could then be used to easily define the presence of residual symptoms. Conclusion Residual symptoms are present in some patients despite their achieving LDA or remission, highlighting an unmet need, especially with respect to improving pain, fatigue, and function. Standardized reporting in future observational studies would facilitate better understanding of this issue in defined RA populations.

This systematic literature review (SLR) regarding the efficacy, duration of use and safety of glucocorticoids (GCs), was performed to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA). Studies on GC efficacy were identified from a separate search on the efficacy of disease-modifying antirheumatic drugs (DMARDs). A combined search was performed for the duration of use and safety of GCs in RA patients. Dose-defined and time-defined GC treatment of any dose and duration (excluding intra-articular GCs) prescribed in combination with other DMARDs were considered. Results are presented descriptively. Two included studies confirmed the efficacy of GC bridging as initial therapy, with equal efficacy after 2 years of initial doses of 30 mg/day compared with 60 mg/day prednisone. Based on a recently performed SLR, in clinical trials most patients starting initial GC bridging are able to stop GCs within 12 (22% patients continued on GCs) to 24 months (10% patients continued on GCs). The safety search included 12 RCTs and 21 observational studies. Well-known safety risks of GC use were confirmed, including an increased risk of osteoporotic fractures, serious infections, diabetes and mortality. Data on cardiovascular outcomes were Inconsistent. Overall, safety risks increased with increasing dose and/or duration, but evidence on which dose is safe was conflicting. In conclusion, this SLR has confirmed the efficacy of GCs in the treatment of RA. In clinical trials, most patients have shown to be able to stop GCs within 12–24 months. Well-known safety risks of GC use have been confirmed, but with heterogeneity between studies.

ObjectivesTo update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA).MethodsThis systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022.ResultsOf 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission.ConclusionThe results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.

Introduction Global prevalence estimates for chronic kidney disease (CKD) in rheumatoid arthritis (RA) vary. This study assessed real-world prevalence estimates of renal impairment, based on estimated glomerular filtration rate (eGFR), among commercially insured patients with RA in the United States (US). Methods In this retrospective cohort study, we used administrative claims data from the HealthCore Integrated Research Database (HIRD®) between January 2013 and December 2018. Adult patients with ≥ 2 claims for RA and ≥ 2 serum creatinine (SCr) measurements ≥ 90 days apart on or after the index date were included. eGFR was calculated per the Modification of Diet in Renal Disease equation. Prevalence of eGFR-based renal impairment was estimated for the overall RA population and for two subgroups: patients on advanced therapies (biologic disease-modifying antirheumatic drugs/tofacitinib) and patients stratified based on health plan types. Results Among 128,062 patients with ≥ 2 RA claims, 42,173 had qualifying SCr measurements, 16,197 were on advanced RA therapies, and 4911 had Medicare Advantage or Supplemental plus Part D coverage. For the overall population and the subgroup on advanced therapies, mild renal impairment was observed in 52% and 51%, moderate renal impairment in 9% and 7%, and severe renal impairment in 0.5% and 0.3% of patients, respectively. Moderate and severe renal impairment was more prevalent in the Medicare Advantage/Supplemental plus Part D population compared to the commercial coverage population. Conclusions Approximately 7–10% of commercially insured adult patients in the US with RA had moderate or severe renal impairment. Assessment of renal function is an important consideration for safe treatment.

Half of the patients with systemic lupus erythematosus (SLE) will have a reduced bone density and more than one in ten will develop osteoporosis (OP) prematurely. Multiple risk factors have been related to loss of bone mass, but just a few are modifiable, such as adequate vitamin D and calcium intakes, weight bearing exercise, controlling SLE activity and limiting the use of glucocorticoids (GC). GC have also been strongly associated to osteonecrosis or avascular necrosis (AVN). The main consequences of OP and AVN are fractures, which lead to significant functional limitation, loss of quality of life and increased morbidity. OP-related fractures can be reduced by performing appropriate screening with bone densitometries and providing prophylactic treatment when long-term or high dose GC are needed. No formal screening is available for AVN; but diagnosis is made by imaging (X-ray, bone scan or advanced imaging where appropriate). Aiming for the lowest dose possible of GC in combination with immunosuppression as well as an early recognition of the symptoms will prevent further complications. This manuscript is a practical review of the epidemiology, pathophysiology, and management of OP and AVN in patients with SLE, based on the available evidence and guidelines. RESUMEN La mitad de los pacientes con lupus eritematoso sistémico (LES) tendrá una densidad ósea disminuida, y más de uno de cada 10 desarrollará osteoporosis (OP) prematuramente. Son múltiples los factores de riesgo que se han relacionado con la pérdida de la masa ósea, pero solo unos pocos son modificables, tales como la ingesta de niveles adecuados de vitamina D y de calcio, ejercicio con pesas, controlar la actividad del LES, y limitar el uso de glucocorticoides (GC). También se ha encontrado una estrecha relación entre el uso de GC y osteonecrosis o a necrosis avascular (NAV). Las principales consecuencias de la OP y de la NAV son fracturas, que generan una limitación funcional importante, pérdida de la calidad de vida y aumento de la morbilidad. Las fracturas por osteoporosis se pueden reducir mediante un tamizaje adecuado con densitometría ósea y administrando tratamiento profiláctico cuando se requieren GC de largo plazo o a altas dosis. No existe un tamizaje formal para la NAV, pero su diagnóstico se realiza con imágenes (radiografía, gammagrafía ósea o imágenes avanzadas cuando corresponda). El apuntar a la menor dosis posible de GC, en combinación con inmunosupresión, además de la temprana identificación de los síntomas, ayudará a prevenir otras complicaciones. El presente artículo es una revisión práctica de la epidemiología, la fisiopatología y el manejo de la OP y la NAV en pacientes con LES, en función de la evidencia y de las guías disponibles.

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.

ObjectiveTo provide the initial installment of a living guideline that will provide up-to-date guidance on the pharmacological management of patients with rheumatoid arthritis (RA) in Canada.MethodsThe Canadian Rheumatology Association (CRA) formed a multidisciplinary panel composed of rheumatologists, researchers, methodologists, and patients. In this first installment of our living guideline, the panel developed a recommendation for the tapering of biologic and targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) therapy in patients in sustained remission using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, including a health equity framework developed for the Canadian RA population. The recommendation was adapted from a living guideline of the Australia & New Zealand Musculoskeletal Clinical Trials Network.ResultsIn people with RA who are in sustained low disease activity or remission for at least 6 months, we suggest offering stepwise reduction in the dose of b/tsDMARD without discontinuation, in the context of a shared decision, provided patients are able to rapidly access rheumatology care and reestablish their medications if needed. In patients where rapid access to care or reestablishing access to medications is challenging, we conditionally recommend against tapering. A patient decision aid was developed to complement the recommendation.ConclusionThis living guideline will provide contemporary RA management recommendations for Canadian practice. New recommendations will be added over time and updated, with the latest recommendation, evidence summaries, and Evidence to Decision summaries available through the CRA website (www.rheum.ca).

Introduction La recherche d’auto-anticorps est un examen tres regulierement utilise dans le cadre du depistage des maladies rhumatismales. Le facteur rhumatoide (FR) et les anticorps anti-nucleaires (ANA) ont une valeur predictive positive tres faible en pratique generale. La surutilisation des tests diagnostiques peut conduire a des orientations inutiles, augmenter l’anxiete des patients et accroitre le budget consacre a la sante. Objectif Nous avions pour objectif d’evaluer les habitudes d’utilisation, la pertinence et les couts lies aux tests de detection des ANA, ENA (antigenes nucleaires solubles), anti-dsDNA, du FR et du HLA-B27 chez des patients orientes en rhumatologie. Methodes Nous avons mene une analyse retrospective des dossiers de patients orientes de maniere consecutive pendant un an (orientations acceptees et rejetees), en s’appuyant sur les pratiques de rhumatologues hospitaliers. Les tests de detection inappropries et les couts inherents a ces examens ont ete analyses. Les tests ont ete consideres comme justifies lorsqu’ils repondaient a au moins un critere pour une maladie specifique. Resultats Parmi les 638 patients consecutifs orientes en rhumatologie, les motifs les plus courants etaient : les spondylarthropathies (SpA), la polyarthrite rhumatoide (PR) et le lupus (LES). Avant leur orientation, 61 % des patients avaient deja ete testes au moins une fois pour les ANA, avec repetition du test ANA dans un tiers des cas ; 19 % avaient passe un test ENA et 21 % un test anti-dsDNA. Dans 20 % des cas, le test ANA a ete realise en l’absence de toute indication clinique. Dans la moitie des cas, les tests anti-ENA et anti-dsDNA ont ete effectues dans un contexte de negativite des ANA. Le depistage du FR a ete demande chez 65 % des patients et dans pres d’1/3 des cas sans aucun diagnostic presomptif d’arthrite inflammatoire. Conclusion Malgre les recommandations de la campagne Choosing Wisely de la SCR (Societe Canadienne de Rhumatologie), au moins 50 % des tests de detection du FR, des ANA, ENA et anti-dsDNA sont prescrits de maniere inappropriee. Une prescription plus selective des tests susmentionnes pourrait conduire a une reduction significative des couts.

Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD). Retrospective study of patients with PAD referred for rheumatologic evaluation prior to starting or during immunotherapy between January 2013 and July 2019 from 10 academic sites across Canada. Data were extracted by chart review using a standardized form. Twenty-seven patients with PAD on ICI therapy were identified. The most common PADs were rheumatoid arthritis (30%), psoriasis/psoriatic arthritis (30%), inflammatory bowel disease (IBD, 15%) and axial spondyloarthritis (11%), and the most frequently observed cancers were lung cancer and melanoma. All patients received anti-PD-1 therapies, and 2 received additional sequential anti-CTLA-4 therapy. PAD exacerbations occurred in 52% over a median (IQR) follow-up of 11.0 (6.0–17.5) months, with 14% being severe, 57% requiring corticosteroids, 50% requiring immunosuppression and 14% requiring ICI discontinuation. Flares were generally more frequent and severe in patients who previously required more intensive immunosuppression (i.e., biologics). Flares occurred despite background immunosuppression at the time of ICI initiation. In patients with preexisting psoriasis, IBD and axial spondyloarthritis, rheumatic immune-related adverse events (irAEs), mostly polyarthritis and tenosynovitis, were frequently observed. Tumor progression was not associated with exposure to immunosuppressive drugs before or after ICI initiation and was numerically less frequent in patients with irAEs. PAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy.

Purpose of review Systemic sclerosis (scleroderma, SSc) is a rare multisystem autoimmune disease characterized by autoantibodies, vasculopathy, and fibrosis of the skin and internal organs. This review aims to provide an overview and summary of the recent epidemiological studies in systemic sclerosis. Recent findings Global trends of scleroderma demonstrate greater prevalence of SSc in European, North, and South American patients compared with East Asian patients. However, the greatest prevalence (47 in 100 000), was found among the indigenous peoples in Canada. Phenotypical differences exist depending on the age of presentation with greater internal organ involvement and disease acceleration present in older patients. Sex differences include greater severity of disease expression, relative prevalence of diffuse cutaneous SSc, and organ involvement in males versus females. New studies conflict with previous data reporting greater proportion of pulmonary arterial hypertension in females. Furthermore, the effect of low median household income is demonstrated as a factor increasing risk of death in SSc patients. Summary Understanding the epidemiological factors in SSc enables patient care through patient classification, prognostication, and monitoring. Future research may emphasize enrichment of SSc patients in randomized trials who are more likely to progress or be treatment responsive, focused screening, and personalized patient care through the creation and validation of new SSc criteria and subsets.

ObjectiveSystemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis.An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria.MethodsMedline, Cochrane MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Web of Science were searched from their inceptions to December 2019 for studies related to SSc subclassification, limited to humans and without language or sample size restrictions.ResultsOf 5686 citations, 102 studies reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or SSc-specific autoantibodies (n = 61), nailfold capillary patterns (n = 29), and molecular, genomic, and cellular patterns (n = 12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality, only subsetting by gene expression signatures in tissue samples has been associated with response to therapy.ConclusionSubsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns, and tissue gene expression signatures have been proposed as innovative means of SSc subsetting.

Rheumatology workforces are increasingly challenged by too few physicians in face of the growing burden of rheumatic and musculoskeletal diseases (RMDs). Rheumatology is one of the most frequent non-surgical specialty referrals and has the longest wait times for subspecialists. We used a population-based approach to describe changes in the rheumatology workforce, patient volumes and geographic variation in the supply of and access to rheumatologists, in Ontario, Canada, between 2000 and 2019, and projected changes in supply by 2030. Over time, we observed greater feminization of the workforce and increasing age of workforce members. We identified a large regional variation in rheumatology supply. Fewer new patients are seen annually, which likely contributes to increasing wait times and reduced access to care. Strategies and policies to raise the critical mass and improve regional distribution of supply to effectively provide rheumatology care and support the healthcare delivery of patients with RMDs are needed.

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

Introduction Autoantibody tests are commonly ordered when screening for rheumatic diseases. Rheumatoid factor (RF) and antinuclear antibody (ANA) have low positive predictive values in general practice. Overuse of diagnostic tests can result in an increase in unnecessary referrals, patient anxiety, and further costs. Objective The objective was to evaluate the utilization patterns, appropriateness, and associated costs of tests including ANA, extractable nuclear antibodies (ENA), anti-double stranded DNA (anti-dsDNA), RF, and HLA-B27 in patients referred to rheumatologists. Methods A review was conducted of consecutive referrals (accepted and rejected) using university rheumatologists’ practices over one year. Inappropriate investigations, and associated costs were analyzed. Tests were considered appropriate if at least one criterion for a specific disease was provided. Results Of 638 referrals the most common reported reasons for referral were: spondyloarthropathies (SpA), rheumatoid arthritis (RA), and lupus (SLE). Prior to referral: 61% had undergone ANA testing at least once, ANA was repeated in one third; 19% had ENA and 21% had anti-dsDNA. 20% had ANA testing with no clinical indication. Half of ENA and anti-dsDNA testing was in the context of a negative ANA. RF was requested in 65% and in close to one third, there was no clinical suspicion of inflammatory arthritis. Conclusion Despite the recommendations by CRA Choosing Wisely Campaign, at least 50% of laboratory investigations, including RF, ANA, ENA, and anti-dsDNA, are inappropriately ordered. More selective ordering of the above tests would lead to marked cost reduction.

Background Clinical practice guidelines recommend screening all systemic sclerosis (SSc) patients for pulmonary arterial hypertension (PAH) with yearly echocardiograms. There is a paucity of evidence to support these guidelines. Research question Can a prediction model identify SSc patients with a very low probability of PAH and therefore not requiring annual screening echocardiogram? Study design and methods We performed a case-control study of 925 unselected SSc subjects nested in a multi-centered, longitudinal cohort. The probability of PAH for each subject was calculated using the results of multivariate logistic regression models. A cut-off was identified for the estimated probability of PAH below which no subject developed PAH (100% sensitivity). Results Study subjects were predominantly female (87.5%), with mean (SD) age 58.6 (11.7) years and disease duration of 18.2 (12.2) years. Thirty-seven subjects developed PAH during 5407.97 person-years of observation (incidence rate 0.68 per 100 person-years). Shortness of breath (SOB), diffusing capacity for carbon monoxide (DLCO) and NT-proBNP were independent predictors of PAH. All SSc-PAH cases had a probability of PAH of >1.1%. Subjects below this cut-off, none of whom had PAH, accounted for 46.2% of the study population. Interpretation A simple prediction model identified subjects at very low probability of PAH who could potentially forego annual screening echocardiogram. This represents almost half of SSc subjects in a general SSc population. This study, which is the first evidence-based study for the rational use of follow-up echocardiograms in an unselected SSc cohort, requires validation. The scoring system is freely available online at http://pahtool.ladydavis.ca.

Digital ulcers (DUs) occur in half of the patients with systemic sclerosis (SSc) and require health care interventions for treatment and monitoring for complications. Our objective was to assess the impact of DUs on resource utilization, including hospitalizations, outpatient visits, and procedures within a large SSc Canadian registry in a matched cohort study.A total of 1,698 SSc patients who completed 1 or more 84-item Resource Utilization Questionnaire (RUQ) for a 12-month recall period between September 2005 and February 2020 were included (9,077 questionnaires). Organ involvement was assessed by the Disease Severity Scale (DSS) on the Medsger scale. Unadjusted and adjusted regression analyses compared the association between DUs and resource utilization.RUQs in 104 SSc patients with active DUs at 2 consecutive annual visits were compared with 104 patients without DUs matched 1:1 for age, sex, disease subtype, and duration. Over 1 year, DUs were associated with a higher number of tests (P ˂ 0.05) and visits to health professionals, especially to a rheumatologist (P ˂ 0.0001) and internist (P = 0.003), a greater need for an accompanying person (P ˂ 0.05) and aids purchased/received (P ˂ 0.05). Having DUs was associated with more severe disease, even after excluding the peripheral vascular domain from a total DSS score (9.7 ± 4.5 versus 5.6 ± 2.7, P ˂ 0.0001). After adjustment for disease severity in other organs, the presence of DUs remained a significant predictor of more frequent physician visits and more tests (P for all ˂ 0.05) by linear regression analysis.SSc patients with DUs used significantly more health care resources per year even after adjustment for disease severity in other organ systems.

Resume Objectifs: cette meta-analyse a etudie la frequence et le type des atteintes oculaires dans les arthrites inflammatoires et d’autres maladies rhumatismales juveniles. Methodes: nous avons recherche les publications relatives aux arthrites et maladies rhumatismales juveniles decrivant la frequence de l’uveite dans un contexte de rhumatisme juvenile et incluant au moins 20 patients dans les bases de donnees Medline, Web of Science et Cochrane, entre leur date de creation et septembre 2018. La prevalence et le type des complications oculaires ont ete extraits et leur frequence a ete estimee par des modeles a effets aleatoires. L’heterogeneite a ete evaluee au moyen du test I2. Resultats: 59 articles resultant de 7 132 citations uniques ont ete inclus. La frequence compilee de l’uveite etait de 24 % dans l’AJI oligoarticulaire, 12 % dans l’AJI polyarticulaire, 1 % dans l’AJI systemique, 50 % dans la maladie de Behcet (MB) juvenile, 9 % dans le rhumatisme psoriasique (RPso) juvenile, 24 % dans la spondyloarthropathie (SpA) juvenile et 5 % dans le lupus erythemateux systemique (LES) juvenile. Le type d’uveite le plus frequent dans l’AJI etait l’uveite anterieure, observee dans 14 % des cas et decrite comme une iridocyclite chez 10 % des patients. Le biais de publication etait negligeable pour toutes les affections a l’exception de celles ayant ete peu etudiees (LES juvenile et AJI systemique). L’uveite dans l’AJI etait plus frequente en Europe (14 %), en Amerique du Nord (11 %) et au Moyen-Orient (12 %) qu’en Asie de l’Est (7 %) et en Oceanie (3 %). Conclusions: l’atteinte oculaire (essentiellement uveite) dans l’arthrite inflammatoire juvenile et d’autres rhumatismes pediatriques variait de 3 a 50 % selon l’affection sous-jacente et etait la plus frequente dans la maladie de Behcet de l’enfant. Parmi les AJI, la frequence de l’uveite la plus elevee a ete constatee dans l’AJI oligoarticulaire et l’uveite anterieure etait le type le plus frequent. Des variations geographiques ont ete observees pour l’uveite dans l’AJI.

Objective.Rheumatoid arthritis (RA) and other rheumatic diseases may present with ocular manifestations.The purpose of our work was to determine the prevalence and type of eye involvement in RA and other connective tissue diseases through a metaanalysis and literature review.Methods.A systematic review of the literature was performed using Medline, Web of Science, and the Cochrane Library from their inceptions until January 7, 2019. Conjunctivitis, keratoconjunctivitis sicca, xeropthalmia, uveitis, eye hemorrhage, optic neuritis, papilledema, orbital disease, retinal artery/vein occlusion, macular edema, retinitis, chorioretinitis, scleritis, iridocyclitits, choroid hemorrhage, blindness, and amaurosis fugax were searched for prevalence in patients with RA, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), dermatomyositis, polymyositis, systemic sclerosis, Sjögren syndrome (SS), undifferentiated connective tissue disease, giant cell arteritis, granulomatosis polyangiitis (GPA; formerly Wegener granulomatosis), systemic vasculitis, and sarcoidosis.Results.There were 3394 studies identified and 65 included. The prevalence of eye involvement was 18% in RA, 26% in GPA, 27% in giant cell arteritis, 27% in sarcoidosis, 31% in SLE, and 35% in APS. The most common manifestation was dry eye syndrome (“dry eye”; keratoconjunctivitis sicca) in most diseases analyzed, with an especially high frequency of 89% in SS. Anterior and posterior uveitis were the most common ocular complications in sarcoidosis, occurring in 16% (95% CI 3–28) and 6% (95% CI 3–9) of patients, respectively.Conclusion.Eye involvement is present in approximately one-fifth of patients with RA, and a one-quarter to one-third of patients with connective tissue diseases (other than SS at 89%) and vasculitis.

Purpose of review The COVID-19 outbreak has resulted in uncertainty for patients with autoimmune rheumatic diseases for several reasons. They are concerned about their risk of developing COVID-19 as many are immune suppressed from their disease and/or treatment, whether they should stop their advanced therapies, if they will have a worse outcome if/when infected due to their underlying medication condition(s) and if they will have drug availability, especially with press (without much data) coverage suggesting hydroxychloroquine may be used in COVID-19 infection causing diversion of medication supply. This article discusses how the pandemic affects people with systemic autoimmune rheumatic diseases. Recent findings Preliminarily, articles seem to suggest that patients with rheumatic diseases may not have more infections from SARS-CoV-2 and similar outcomes to age and gender matched patients, but fear of rheumatic medications increasing their risk, drug shortages, and work exposure all are concerns for patients. Recent findings The long term effects of the pandemic in patients with rheumatic diseases will not be known until much later and likely include stressors flaring disease (fear, illness, job loss, social isolation), post-traumatic stress, flaring due to stopping medications, less physician visits with subsequent under-treatment, and increases in chronic concomitant fatigue, pain, fibromyalgia.

Introduction Janus kinase (JAK) inhibitors are a class of targeted therapies for rheumatoid arthritis (RA) with established clinical efficacy. However, little is known about their efficacy compared with each other. This network meta-analysis (NMA) estimated the comparative efficacy of JAK inhibitors currently approved for RA. Methods A targeted literature review was conducted for phase III randomized controlled trials (RCTs) evaluating the efficacy of three approved JAK inhibitors (tofacitinib, baricitinib, and upadacitinib) as monotherapy or combination therapy among patients with moderate-to-severe RA who had inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR). Using Bayesian NMA, American College of Rheumatology (ACR) 20/50/70 responses and clinical remission (defined as DAS28-CRP

Objective To estimate trends in the incidence and prevalence of GCA over time in Canada. Methods We performed a population-based study of Ontario health administrative data using validated case definitions for GCA. Among Ontario residents ≥50 years of age we estimated the annual incidence and prevalence rates between 2000 and 2018. We performed sensitivity analyses using alternative validated case definitions to provide comparative estimates. Results Between 2000 and 2018 there was a relatively stable incidence over time with 25 new cases per 100 000 people >50 years of age. Age-standardized incidence rates were significantly higher among females than males [31 cases (95% CI: 29, 34) vs 15 cases (95% CI: 13, 18) per 100 000 in 2000]. Trends in age-standardized incidence rates were stable among females but increased among males over time. Incidence rates were highest among those ≥70 years of age. Standardized prevalence rates increased from 125 (95% CI 121, 129) to 235 (95% CI 231, 239) cases per 100 000 from 2000 to 2018. The age-standardized rates among males rose from 76 (95% CI 72, 81) cases in 2000 to 156 (95% CI 151, 161) cases per 100 000 population in 2018. Between 2000 and 2018, the age-standardized rates among females similarly increased over time, from 167 (95% CI 161, 173) to 304 (95% CI 297, 310) cases per 100 000 population. Conclusion The incidence and prevalence of GCA in Ontario is similar to that reported in the USA and northern Europe and considerably higher than that reported for southern Europe and non-European populations.

Summary Strides have been made in the treatment of pulmonary arterial hypertension and interstitial lung disease in patients with systemic sclerosis, with successful trials of combination therapies in pulmonary arterial hypertension and of new drugs that slow the decline of lung function in interstitial lung disease. However, many trials in patients with early diffuse cutaneous systemic sclerosis have been negative, including trials of tocilizumab, abatacept, and riociguat, despite improvements in skin scores and other endpoints that approached statistical significance. Trials of macitentan for digital ulcers in these patients have also been disappointing. Trials that do not meet their primary endpoint do not necessarily signify ineffective therapies, as there are many other possible reasons for negative trial results, including features of trial design, insufficient trial duration, or insufficient power to detect differences between groups. In this Series paper, I discuss some of these reasons and what the research community can learn from negative trials to inform future trial design going forward.

ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

ObjectivesTo characterise infections in patients with rheumatoid arthritis (RA) in ORAL Surveillance.MethodsIn this open-label, randomised controlled trial, patients with RA aged≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg two times per day or a tumour necrosis factor inhibitor (TNFi). Incidence rates (IRs; patients with first events/100 patient-years) and hazard ratios (HRs) were calculated for infections, overall and by age (50–ResultsIRs/HRs for all infections, serious infection events (SIEs) and non-serious infections (NSIs) were higher with tofacitinib (10>5 mg two times per day) versus TNFi. For SIEs, HR (95% CI) for tofacitinib 5 and 10 mg two times per day versus TNFi, respectively, were 1.17 (0.92 to 1.50) and 1.48 (1.17 to 1.87). Increased IRs/HRs for all infections and SIEs with tofacitinib 10 mg two times per day versus TNFi were more pronounced in patients aged≥65 vs 50–ConclusionsInfections were higher with tofacitinib versus TNFi. Findings may inform future treatment decisions.Trial registration numberNCT02092467.

Advances in our understanding of interstitial lung disease (ILD) pathophysiology and natural history have led to the development of guidelines for the diagnosis and management of several of these complex diseases. The demographics of patients with ILD indicate the disease is not restricted to older adults. Connective tissue disease-associated ILD, familial pulmonary fibrosis, and post-COVID-19 fibrosis may affect women of child-bearing age. Recent trials have excluded pregnant women, thereby limiting the applicability of contemporary therapeutic advances to these patients. This review synthesizes the current knowledge of pregnancy outcomes in those with ILD, with a focus on connective tissue disease-associated ILD, and potential treatment implications for patients with ILD who are pregnant or considering pregnancy. Pregnancy considerations for patients with ILD include the need for preconception counseling and planning to ensure disease stability, medication and vaccination optimization, and multidisciplinary involvement of a patient's pulmonologist, obstetrician, and, when indicated, rheumatologist and genetic counselor. Evidence to date suggests that women with ILD can have safe and healthy pregnancies but that complications may occur in those with severe ILD.

Medical cannabis is often used to alleviate common symptoms in patients with chronic conditions. With cannabis legalisation in Canada and easier access, it is important that rheumatologists understand its potential impact on their practice. Among patients attending rheumatology clinics in Ontario we assessed: the prevalence of medical cannabis use; symptoms treated; rheumatologists' perceptions.Eight rheumatology clinics recruited consecutive adult patients in a 3-part medical cannabis survey: the first completed by rheumatologists; the second by all patients; the third by medical cannabis users. Student's t-test and Chi-square test were used to compare medical cannabis users to never users.799 patients participated, 163 (20.4%) currently using medical cannabis or within2 years and 636 never users; most had rheumatoid arthritis (37.8%) or osteoarthritis (34.0%). Compared to never users, current/past-users were younger; more likely to be taking opioids/anti-depressants, have psychiatric/gastrointestinal disorders, and have used recreational cannabis (p0.05); had higher physician (2.9 vs. 2.1) and patient (6.0 vs. 4.2) global scores, and pain (6.2 vs. 4.7) (p0.0001). Pain (95.5%), sleeping (82.3%) and anxiety (58.9%) were the most commonly treated symptoms; 78.2% of current/past-users reported medical cannabis was at least somewhat effective. Most rheumatologists reported being uncomfortable to authorise medical cannabis, primarily due to lack of evidence, knowledge, and product standardisation.Medical cannabis use among rheumatology patients in Ontario was two-fold higher than that reported for the general population of similar age. Use was associated with more severe disease, pain, and prior recreational use. Reported lack of research, knowledge, and product standardisation were barriers for rheumatologist use authorisation.

Background Patient-reported outcomes (PROs) are important when evaluating treatment benefits in rheumatoid arthritis (RA). We compared upadacitinib, an oral, selective JAK-1 inhibitor, with placebo to assess clinically meaningful improvements in PROs in patients with RA who have had inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARD-IR). Methods PRO responses between upadacitinib 15 mg or 30 mg and placebo were evaluated at week 12 from the SELECT-BEYOND trial. Improvement was determined by measuring Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36), duration and severity of morning (AM) stiffness, and Insomnia Severity Index (ISI). Least squares mean changes and percentage of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores greater than or equal to normative values were determined. The number needed to treat (NNT) to achieve clinically meaningful improvements was calculated. Results In 498 patients, both upadacitinib doses resulted in statistically significant changes from baseline versus placebo in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 7 of 8 SF-36 domains (15 mg), 6 of 8 SF-36 domains (30 mg), and AM stiffness duration and severity. Compared with placebo, more upadacitinib-treated patients reported improvements ≥ MCID in PtGA, pain, HAQ-DI, SF-36 PCS, 7 of 8 SF-36 domains (15 mg), 5 of 8 SF-36 domains (30 mg), AM stiffness duration and severity, and ISI (30 mg) and scores ≥ normative values in HAQ-DI and SF-36 domains. Across most PROs, NNTs to achieve MCID with upadacitinib ranged from 4 to 7 patients. Conclusions In bDMARD-IR RA patients, upadacitinib (15 mg or 30 mg) improved multiple aspects of quality of life, and more patients reached clinically meaningful improvements approaching normative values compared with placebo. Trial registration The trial is registered with ClinicalTrials.gov (NCT02706847), registered 6 March 2016.