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Background: In 2021, an EULAR task force published a definition of difficult-to-treat rheumatoid arthritis (D2T RA). Our current knowledge of D2T RA with the EULAR definition is based on European and Asian cohorts, and no North American cohort has yet to be published. The aim of this study was to compare D2T RA patients to non-D2T RA who are good responders to advanced therapy, and to describe their evolution in an university health center patient cohort., Methods: This is a retrospective single centre study of the medical records of all adults with RA on at least one biologic or target synthetic DMARD (b/tsDMARD). D2T RA group was defined according to the EULAR definition of D2T RA. The non-D2T RA group was defined as a b/tsDMARD good responder who had low-disease activity or remission for at least one year on 1 or 2 b/tsDMARD mechanism of action. We compared the patients' comorbidities, and history of b/tsDMARD use. Descriptive statistics and proportions were calculated. Kaplan-Meier analysis with log-rank test was used to estimate and compare median survival., Results: Among the 417 patients, 101 (24%) were D2T RA and 316 (76%) were non-D2T RA. D2T RA group was slightly younger (63 ± 9 years versus 65 ± 12 years, p = 0.045), more likely to have concomitant non-inflammatory pain (28% versus 8%, p < 0.0001) and to discontinue at least one b/tsDMARD due to intolerance (39% versus 10%, p < 0.0001). In the D2T RA group, JAK inhibitors were associated with longer drug continuation when used as the third b/tsDMARD. Fewer patients were using corticosteroid at their most recent follow-up in this Canadian cohort compared to others (16% versus from 29 to 74%)., Conclusion: Concomitant non-inflammatory pain was more prevalent in D2T RA patients compared to b/tsDMARD good responder non-D2T RA patients. Steroid-sparing strategies is possible even in D2T RA patients. Future prospective research may compare JAK inhibitors with other mechanisms of action in D2T RA., (© 2024. The Author(s).)

Objective: Treat-to-target (T2T) is recommended in the management of rheumatoid arthritis (RA) but its implementation is suboptimal. We aimed to identify interventional strategies targeted at improving T2T implementation in RA by systematically reviewing published evidence on barriers to, facilitators of, and interventions to support T2T implementation., Methods: Systematic and scoping literature searches in PubMed/MEDLINE®, BIOSIS Previews®, Derwent Drug File, Embase®, EMCare®, International Pharmaceutical Abstracts, and SciSearch® were conducted to identify barriers/facilitators and interventions relating to T2T implementation in RA. The quality of included studies was assessed using Critical Appraisal Skills Programme (CASP) checklists. Data related to barriers/facilitators and interventions were extracted, grouped, and summarized descriptively, and a narrative synthesis was generated., Results: In total, 146 articles were analyzed, of which 123 (84%) included ≥50% of the items assessed by CASP checklists. Of the 146 studies, 76 evaluated T2T barriers and facilitators, from which 329 relevant statements were identified and regrouped into 18 target areas, including: healthcare professionals' (HCPs') or patients' knowledge or perceptions; patient-HCP communication or alignment; and time or resources. Overall, 56 interventions were identified from 70 studies across the 18 target areas; 54% addressed disease activity or patient-reported outcome assessments. Of the 56 interventions identified, 36 improved T2T implementation and/or patient outcomes in RA., Conclusion: Despite long-established T2T recommendations, there remain many barriers to its implementation. Interventions to improve T2T should be developed further and assessed, with a particular focus on tailoring them to individual countries, regions, and healthcare settings., (This article is protected by copyright. All rights reserved.)

Objective: To provide a set of living treatment recommendations that will give contemporary guidance on the management of patients with axial spondyloarthritis (axSpA) in Canada., Methods: The Spondyloarthritis Research Consortium of Canada (SPARCC), in conjunction with the Canadian Rheumatology Association, organized a treatment recommendations panel composed of rheumatologists, researchers, allied health professionals, and a patient advocate. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach was used, in which existing guidelines were adopted or adapted to a Canadian context. Recommendations were also placed in a health equity framework., Results: Fifty-six recommendations were made for patients with active axSpA, stable axSpA, active or stable axSpA, for comorbidities, and for assessment, screening, and imaging. Recommendations were also made for principles of management, disease monitoring, and ethical considerations., Conclusion: These living treatment recommendations will provide up-to-date guidance for the management of axSpA for Canadian practice. As part of the living model, they will be updated regularly as changes occur in the treatment landscape.

Background/objective: In patients with rheumatoid arthritis (RA), high tender-swollen joint differences (TSJDs) have been associated with worse outcomes. A better understanding of the phenotype and impact of high TSJD on patient-reported outcomes (PROs) in early RA may lead to earlier personalized treatment targeting domains that are important to patients today. Our objectives were to evaluate the impact of TSJD on updated PROs in patients with early RA over 1 year and to determine differences in associations by joint size., Methods: This longitudinal cohort study followed patients with active, early RA enrolled in the Canadian Early Arthritis Cohort between 2016 and 2022, who completed clinical assessments and PROMIS-29 measures over 1 year. Twenty-eight joint counts were performed and TSJDs calculated. Adjusted associations between TSJD and PROMIS-29 scores were estimated using separate linear-mixed models. Separate analyses of large versus small-joint TJSDs were performed., Results: Patients with early RA (n = 547; 70% female; mean [SD] age, 56 [15] years; mean [SD] symptom duration, 5.3 [2.9] months) were evaluated. A 1-point increase in TSJD was significantly associated with worse PROMIS T-scores in all domains: physical function (adjusted regression coefficient, -0.27; 95% confidence interval [CI], -0.39, -0.15), social participation (adjusted regression coefficient, -0.34; 95% CI, -0.50, -0.19), pain interference (adjusted regression coefficient, 0.49; 95% CI, 0.35, 0.64), sleep problems (adjusted regression coefficient, 0.29; 95% CI, 0.16, 0.43), fatigue (adjusted regression coefficient, 0.34; 95% CI, 0.18, 0.50), anxiety (adjusted regression coefficient, 0.23; 95% CI, 0.08, 0.38), and depression (adjusted regression coefficient, 0.20; 95% CI, 0.06, 0.35). Large-joint TSJD was associated with markedly worse PROs compared with small-joint TSJD., Conclusions: Elevated TSJD is associated with worse PROs particularly pain interference, social participation, and fatigue. Patients with more tender than swollen joints, especially large joints, may benefit from earlier, targeted therapeutic interventions., Competing Interests: There is no financial support or other benefits from commercial sources for the work reported on in the manuscript or any other financial interests that any of the authors may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS) <1.3) or at least low disease activity (LDA; 1.3≤ASDAS<2.1).To investigate the association between treatment response at week 12 and/or week 24 and attainment of the ASDAS<2.1 treat-to-target recommendation at week 52 in bDMARD-naïve patients with radiographic (r-)axSpA treated with ixekizumab (IXE)., Methods: This post hoc analysis included patients randomly assigned to IXE 80 mg every 4 weeks from COAST-V (NCT02696785), a phase 3 trial in bDMARD-naïve patients with r-axSpA. The proportion of patients who achieved ASDAS<2.1 at week 52 was measured among those who attained or not clinically important improvement (CII, ∆ASDAS≥1.1) response, and among those with ID, LDA and high or very high disease activity at week 12 and/or week 24. Non-response was assumed for missing data., Results: Amongst 81 patients, 47 (58.0%) achieved ASDAS CII at week 12, with 70.2% (n=33) achieving ASDAS<2.1 at week 52. At week 24, 52 (64.2%) patients achieved ASDAS CII, with 71.2% (n=37) achieving ASDAS<2.1 at week 52. Of the 24 patients who did not achieve ASDAS CII at either week 12 or week 24, 5 (20.8%) achieved ASDAS<2.1 at week 52., Conclusion: This analysis reinforces the current recommendation that continuing treatment in those achieving ASDAS CII at week 12 and/or week 24 increases the likelihood of obtaining ID/LDA at week 52., Trial Registration Number: NCT02696785., Competing Interests: Competing interests: SR has received speaker and/or consultation fees and/or research support/grants from AbbVie, Eli Lilly and Company, Galapagos NV, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi and UCB Pharma. CL has received speaker and/or consultation fees and/or research support/grants from AbbVie, Amgen, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly and Company, Galapagos NV, Merck Sharp & Dohme, Novartis, Pfizer and Roche. LB has received speaker and/or consultation fees and/or research support/grants from Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Sanofi, Eli Lilly and Company, Gilead, JAMP Pharma, Fresenius Kabi, Teva, Organon and Sandoz. PW has received consulting payments, research funding, and/or honoraria from Abbvie, Amgen, Novartis, Eli Lilly and Company, Sanofi-Genzyme, SetPoint, Sun Pharma, Viela Bio, RegenLab, Paradigm, AstraZeneca, Janssen, Horizon and LG Chem. TP is an employee and shareholder of Eli Lilly and Company. RB is an employee and shareholder of Eli Lilly and Company. SL-L is a former employee of Eli Lilly and Company. BJ is an employee and shareholder of Eli Lilly and Company. MJN has received speaker and/or consultation fees and/or research support/grants from AbbVie, Amgen, Celgene, Eli Lilly and Company, Janssen, Novartis and Pfizer and has received grant and/or research support from Novartis. JC-CW has received speaker and/or consultation fees and/or research support/grants from AbbVie, Bristol Myers Squibb, Celgene, Chugai Pharmaceutical, Eisai, Eli Lilly and Company, Janssen, Novartis, Pfizer, Sanofi-Aventis, TSH Biopharm and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA., Methods: Eligible patients had received MTX for ≥ 3 months before b/tsDMARD initiation. The b/tsDMARD was prescribed continuously for ≥ 18 months. Patients taking > 10 mg/day oral prednisone or equivalent were excluded., Results: Eight hundred eighty-nine patients (mean baseline MTX dose 19.0 mg/week) prescribed b/tsDMARDs (tumor necrosis factor inhibitor 52.1%, Janus kinase inhibitor 18.3%, interleukin-6 inhibitor [IL-6i] 11.9%, other 17.7%) were evaluated at 22 Canadian centers. Within 2 years of b/tsDMARD initiation, MTX was tapered in 123 (13.8%) patients and discontinued in 147 (16.5%), most commonly due to planned tapering (36.6%) and patient decision (27.2%), respectively, and most commonly with IL-6i use (34.9%). The MTX dose was unchanged for 582 (65.5%) patients and increased for 37 (4.2%). Missing data limit interpretations of MTX dose effects on some secondary endpoints and challenge the assertion that a disease activity measure-based treat-to-target approach is routinely used in Canadian rheumatology practice., Conclusions: Methotrexate tapering or withdrawal occurred in 30.4% of Canadians with RA within 2 years following b/tsDMARD initiation. Baseline disease activity measures were missing from many medical records. However, for patients with baseline assessments, MTX tapering or discontinuation did not worsen disease activity., (© 2024. The Author(s).)

Objectives: Standard criteria for measuring treatment efficacy in patients with rheumatoid arthritis (RA) include American College of Rheumatology (ACR) response rates, which require meeting a threshold of ≥20/50/70% improvement in several physician- and patient-reported measures. We aimed to evaluate the impact of csDMARDs, TNF inhibitors (TNFi), and tofacitinib (TOFA) on ACR components in real-life practice., Methods: Clinical data of RA patients with a CDAI >10 at the time they started a treatment were pooled from two registries: Ontario Best Practices Research Initiative (OBRI) and RHUMADATA. Endpoints included proportions of patients achieving: ACR20/50/70 responses, ≥20/50/70% improvements and mean percentage improvement in individual ACR components at Month 6. We also adjusted for potential confounders to compare impact of these medications on outcomes of interest., Results: A total of 669 patients were included (csDMARD, n=157, TNFi, n=252; TOFA, n=260). An overall higher proportion in all three-medication groups achieved ≥20/50/70% improvement in primary ACR components vs. secondary components. Among secondary components, ≥20/50/70% improvement rates were numerically highest for PhGA and lowest for HAQ-DI and pain. Among ACR20/50/70 responders for all medications, the mean percentage improvement was more than 80% for primary components, and ranged from 30% to 80% for secondary components. A significantly lower proportion of patients in TNFi group achieved to at least 50% improvement in pain compared to TOFA after adjusting., Conclusions: In this real-world practice, physician-reported measures contribute slightly more to overall ACR20/50/70 responses. Pain was the most important factor in achieving an ACR50 TOFA users, possibly reflecting the different effects of JAKi on pain.

Background: Since 2000, advanced therapies (AT) have revolutionized the treatment of moderate to severe rheumatoid arthritis (RA). Randomized control trials as well as observational studies together with medication availability often determine second-line choices after the failure of first Tumor Necrosis Factor inhibitors (TNFi). This led to the observation that specific sequences provide better long-term effectiveness. We investigated which alternative medication offers the best long-term sustainability following the first TNFi failure in RA., Methods: Data were extracted from RHUMADATA from January2007. Patients were followed until treatment discontinuation, loss to follow-up, or November 25, 2022. Kaplan-Meier and Cox regression models were used to compare discontinuation between groups. Missing data were imputed, and propensity scores were computed to reduce potential attribution bias. Complete, unadjusted, and propensity score-adjusted imputed data analyses were produced., Results: 611 patients (320 treated with a TNFi and 291 treated with molecules having another mechanism of action (OMA)) were included. The mean age at diagnosis was 44.5 and 43.9 years, respectively. The median retention was 2.84 and 4.48 years for TNFi and OMAs groups. Using multivariable analysis, the discontinuation rate of the OMA group was significantly lower than TNFi (adjHR: 0.65; 95% CI: 0.44-0.94). This remained true for the PS-adjusted MI Cox models. In a stratified analysis, rituximab (adjHR: 0.39; 95% CI: 0.18-0.84) had better retention than TNFi after adjusting for patient characteristics., Conclusion: Switching to an OMA, especially rituximab, in patients with failure to a first TNFi appears to be the best strategy as a second line of therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA., Methods: Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP) < 2.6 at 6 months. Data was collected at routine visits. Data analysed and summarised descriptively for the overall interim population and for subgroups based on prior therapy included remission or low disease activity, patient-reported outcomes (PROs), and adverse events., Results: A total of 392 patients were included in the interim analysis. Overall, 63.5% (191/301) of patients achieved a DAS28-CRP score < 2.6 at month 6, with similar rates observed for all subgroups analysed according to prior therapy including those with prior JAK inhibitor exposure (range 57.4-71.0%), and in patients who received UPA monotherapy (71.6% [48/67]). Early (month 3) and sustained improvements up to 6 months were observed for all PROs. The safety profile was consistent with previous reports., Conclusion: Real-world improvements in disease activity and PROs in response to UPA treatment were consistent with clinical trial data across a range of Canadian patients with prior therapy exposure and with UPA monotherapy, with an overall favourable benefit-risk profile., Trial Registration: NCT04574492., (© 2024. The Author(s).)

Introduction: This study aimed to describe the long-term efficacy and safety of upadacitinib and adalimumab through 228 weeks following immediate switch to the alternate therapy with a different mechanism of action (MoA) in patients with rheumatoid arthritis (RA) not achieving treatment goals with their initial randomized therapy in the ongoing phase 3 SELECT-COMPARE study., Methods: Patients with non-response or incomplete response to initially prescribed upadacitinib 15 mg once daily or adalimumab 40 mg every other week were switched to the alternate therapy by week 26. Efficacy was evaluated through 228 weeks post-switch using validated outcome measures, including Clinical Disease Activity Index (CDAI) low disease activity (LDA; ≤ 10)/remission (≤ 2.8); 28-joint Disease Activity Score based on C-reactive protein ≤ 3.2/< 2.6; ≥ 20%/50%/70% improvement in American College of Rheumatology (ACR) response criteria; and change from baseline in ACR core components. Data are reported as observed. Safety was assessed by treatment-emergent adverse events (TEAEs) through week 264., Results: Of patients initially randomized to upadacitinib and adalimumab, 38.7% and 48.6%, respectively, switched to the alternate therapy by week 26. Clinically relevant improvements in all efficacy measures were observed through 228 weeks post-switch and were generally similar between groups, with small numeric differences mostly in favor of switching to upadacitinib. CDAI remission was achieved by 32.7% and 28.6% of initial non-responders, and 27.5% and 27.3% of incomplete responders, while CDAI LDA was achieved by 76.9% and 72.9% of non-responders, and 72.5% and 72.7% of incomplete responders switching to upadacitinib and to adalimumab, respectively. TEAE rates were similar between groups, although herpes zoster infection, lymphopenia, and creatine phosphokinase elevation were more frequent when switching to upadacitinib. No new safety signals were identified., Conclusion: Switching to a different MoA may provide long-term benefit to patients with RA not achieving treatment goals with their initial therapy, with acceptable safety profiles., Trial Registration: NCT02629159., (© 2024. The Author(s).)

Objective: Patients with early rheumatoid arthritis (RA) may present with more tender than swollen joints, which can persist. Elevated tender-swollen joint difference (TSJD) is often challenging, because there may be multiple causes and it may contribute to overestimating disease activity. Little is known about the phenotype and impact of TSJDs on patient function. Our objective was to evaluate the impact of TSJD on functional outcomes in early RA and to see whether associations vary by joint size., Methods: Data were from patients with active, early RA (≤12 months) enrolled in the Canadian Early Arthritis Cohort, who completed assessments of general function (Multidimensional Health Assessment Questionnaire [MDHAQ]), upper extremity (UE) function (Quality of Life in Neurological Disorders [Neuro-QoL] UE scale), and work/activity impairment (Work Productivity and Activity Impairment RA) over their first year of follow-up. A total of 28 joint counts were performed. TSJDs were calculated. Adjusted associations between TSJDs and functional outcomes were estimated in separate multivariable linear mixed effects models. Separate analyses were performed for large- versus small-joint TSJD., Results: Patients (N = 547) were 70% female, mean age 56 (SD 15) years, mean disease duration 5.3 (SD 2.9) months. At baseline, 287 (52%) had TSJD >0 (43% involved large joints and 34% small joints), decreasing to 32% at 12 months. A one-point increase in TSJD was significantly associated with worse function (MDHAQ: adjusted mean change 0.10, 95% confidence interval [CI] 0.08-0.13; Neuro-QoL UE function T score: adjusted mean change -0.59, 95% CI -0.76 to -0.43; and greater work impairment: adjusted mean change 1.95%, 95% CI 0.85%-3.05%). Higher large-joint TSJDs were associated with the worst functional outcomes., Conclusion: Having more tender than swollen joints is common in early RA and is associated with worse function, most notably when involving large joints. Early identification and targeted intervention strategies may be needed., (© 2024 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years., Methods: Patients with rheumatoid arthritis and inadequate response to methotrexate were randomised to receive upadacitinib 15 mg once daily, placebo or adalimumab 40 mg every other week, all with concomitant methotrexate. By week 26, patients with insufficient response to randomised treatment were rescued; patients remaining on placebo switched to upadacitinib. Patients completing the 48-week double-blind period could enter a long-term extension. Safety and efficacy were assessed through week 264, with radiographic progression analysed through week 192. Safety was assessed by treatment-emergent adverse events (TEAEs). Efficacy was analysed by randomised group (non-responder imputation (NRI)) or treatment sequence (as observed)., Results: Rates of TEAEs were generally similar with upadacitinib versus adalimumab, although numerically higher rates of herpes zoster, lymphopenia, creatine phosphokinase elevation, hepatic disorder and non-melanoma skin cancer were reported with upadacitinib. Numerically greater proportions of patients randomised to upadacitinib versus adalimumab achieved clinical responses (NRI); Clinical Disease Activity Index remission (≤2.8) and Disease Activity Score based on C reactive protein <2.6 were achieved by 24.6% vs 18.7% (nominal p=0.042) and 31.8% vs 23.2% (nominal p=0.006), respectively. Radiographic progression was numerically lower with continuous upadacitinib versus adalimumab at week 192., Conclusion: The safety profile of upadacitinib through 5 years was consistent with the known safety profile of upadacitinib, with no new safety risks. Clinical responses were numerically higher with upadacitinib versus adalimumab at 5 years. Upadacitinib demonstrates a favourable benefit-risk profile for long-term rheumatoid arthritis treatment., Trial Registration Number: NCT02629159., Competing Interests: Competing interests: RF has received consulting fees and/or grant/research support from AbbVie, Amgen, BI, Biosplice, BMS, Flexion, Galapagos, Galvani, Gilead, GSK, Horizon, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, Selecta, UCB, Viela, Vorso and Vyne and has participated on a data safety monitoring board or advisory board for Kiniksa. JS has received speaking fees, consulting fees and grant/research support from AbbVie, Accord, BMS, Janssen, MSD, Pfizer, Roche, Sandoz and UCB. SKP, XB, NK and YL are employees of AbbVie and may hold stock or options. PD has received speaker fees from AbbVie, Galapagos, Lilly, Nordimed and Thermofischer. LB has received speaking fees, consulting fees and grant/research support from AbbVie, Amgen, BMS, Celgene, Lilly, Fresenius Kabi, Gilead, Janssen, Novartis, Organon, Pfizer, Sanofi-Aventis, Teva and UCB. CGP is an employee and shareholder of Spire Sciences and has served as a consultant for Aclaris, AstraZeneca, Daiichi-Sankyo, Five Prime, Genentech, Gilead, GSK, Istesso, Labcorp, Lilly, Pacira, Paradigm, SetPoint, Sorrento, SynOx and UCB. YT has received speaker fees and/or honoraria from AbbVie, Asahikasei, AstraZeneca, BI, BMS, Chugai, Eisai, Gilead, GSK, Lilly, Pfizer, Taiho and Taisho and research grants from Asahikasei, Chugai, Eisai, Mitsubishi-Tanabe and Taisho. EM has received speaking fees, consulting fees and grant/research support from AbbVie, Amgen, AstraZeneca, BMS, Hi-Bio, Janssen, Lilly, Novartis, Pfizer, Roche, Sandoz and Sanofi, and has received payment for expert testimony from AbbVie., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Hypertension (HTN) is a common comorbidity in RA. This study aimed to explore the prevalence and incidence of HTN and baseline factors associated with incident HTN in early RA (ERA)., Methods: Data were from the Canadian Early Arthritis Cohort (CATCH), an inception cohort of ERA patients having <1 year of disease duration. HTN was determined by patient- or physician-reported diagnosis, the use of anti-hypertensives and/or blood pressure. Multivariable logistic regression was performed to determine baseline factors associated with prevalent and incident HTN in this population., Results: The study sample included 2052 ERA patients [mean age 55 years (s.d. 14), 71% female). The prevalence of HTN at study enrolment was 26% (23% in females and 34% in males). In both sexes, prevalent HTN was associated with older age, diabetes and hyperlipidaemia. HTN was associated with being overweight or high alcohol consumption in females. Of the RA patients who did not have HTN at enrolment, 24% (364/1518) developed HTN during the median follow-up period of 5 years (range 1-8). Baseline factors significantly associated with incident HTN were older age, being overweight, excess alcohol consumption and having hyperlipidaemia. Incident HTN was associated with high alcohol consumption in males and with hyperlipidaemia in females. RA-associated disease factors and treatments were not significantly associated with prevalent or incident HTN., Conclusions: Early RA patients had a high incidence of hypertension with the highest risk in older patients with traditional cardiovascular risk factors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction: The APPRAISE study was conducted to better understand the 12-month effectiveness, tolerability, and patient satisfaction with apremilast treatment for patients with psoriatic arthritis (PsA) in real-world settings., Methods: APPRAISE (NCT03608657), a prospective, multicenter, observational study, enrolled adults with active PsA prescribed apremilast per routine care between July 2018 and March 2020. Patients were followed for 12 months with visits suggested every 4 months. The primary outcome measure was achievement of remission (REM) or low disease activity (LDA), defined as a Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score ≤ 13., Results: Of the 102 patients who enrolled, 45 (44.1%) discontinued the study by 12 months. Most patients (75.5%) had moderate or high disease activity, and 24.5% were in REM/LDA at baseline based on cDAPSA score. Achievement of cDAPSA REM/LDA was 63.7%, 67.2%, and 53.8% at months 4, 8, and 12, respectively. In those continuing in the study, significant improvements were seen in swollen and tender joint counts, pain visual analog scale, psoriasis body surface area, and complete dactylitis resolution. Enthesitis reduction was also observed. Improvements in treatment satisfaction and patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and the 36-item Short Form physical and mental component scores, were observed over 12 months. The proportion of patients achieving a Patient-Acceptable Symptom State (PASS) increased significantly from baseline at months 4, 8, and 12 (P < 0.001). Apremilast was well tolerated; the most frequent adverse events (AEs) leading to discontinuation were diarrhea (9/102 [8.8%]), nausea (4/102 [3.9%]), and migraine (4/102 [3.9%])., Conclusion: In this real-world study conducted in Canadian rheumatology clinics, apremilast demonstrated clinical effectiveness in patients with active PsA, along with patient satisfaction with treatment. Safety findings were consistent with previously reported clinical data., Trial Registration: ClinicalTrials.gov identifier, NCT03608657., (© 2024. The Author(s).)

Introduction: Our aim was to investigate the efficacy and safety of upadacitinib (UPA) in patients with either oligo- or polyarticular active psoriatic arthritis (PsA) using routine clinical practice data from an observational, prospective, multicentre study., Methods: This interim analysis contains upadacitinib efficacy and safety data from the UPJOINT study, collected from baseline to the week 24 visit with a focus on composite measures, clinical assessments and patient-reported outcomes, amongst others, including minimal disease activity (MDA), very low disease activity (VLDA), Disease Activity Index for Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI), resolution of dactylitis and nail psoriasis and body surface area affected by skin psoriasis (BSA)., Results: A total of 296 patients with baseline data and 192 with completed week 24 visits were included in the analysis. The proportion of patients achieving MDA increased from 2.7% at baseline to 39.1% at week 24 (95% CI 32.1, 46.3). Similarly, the number of patients in DAPSA remission (DAPSA ≤ 4) increased from 0 at baseline to 32 (16.7%) by week 24. At that time, 59.4% of the patients were either in DAPSA remission or had low disease activity (DAPSA ≤ 14). During the 24 weeks time frame, the proportion of patients with BSA ≤ 3 increased from 80.7% to 91.1%. Furthermore, at weeks 12 and 24, 45.14% and 47.19% of affected patients showed a resolution of enthesitis. Active dactylitis and nail psoriasis at baseline were reported to affect 10.5% and 22.0%, decreasing to 2.6% and 5.7% at week 24, respectively. The safety findings are consistent with the known safety profile of upadacitinib in rheumatoid arthritis and PsA; no new safety risks were identified., Conclusion: The data from this study confirm the findings of previous randomized controlled trials suggesting UPA is an effective treatment for active PsA without any new safety signals in patients from daily clinical practice., Clinical Trial Registration: ClinicalTrials.gov identifier, NCT04758117., (© 2023. The Author(s).)

Objective: To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease., Methods: We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed., Results: Frequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2-53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection., Conclusion: In COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection., Competing Interests: Competing interests: IC, VV, NA, MU, ER, LF, ER-L, M-AF, EH, DM, LM, PP, M-AL, SB, PRF—no competing interests. LB received grants or has contracts with Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Gilead, JAMP Pharma., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The type of failure may predict response to a second biologic. We evaluated the response to a second tumor necrosis factor inhibitor (TNFi) or non-TNFi in patients failing their initial TNFi, either primarily or secondarily., Methods: Patients with rheumatoid arthritis who were biologic-naive and had a Clinical Disease Activity Index (CDAI) >10, who started their first TNFi for ≥3 months and then switched to a second biologic, were included in the study. Secondary failure was defined as 2 consecutive low-CDAI visits and then switching to a second biologic while they had moderate/severe CDAI. Primary failure was defined if it did not meet the definition of secondary failure, or if they had at least 1 moderate/severe CDAI after 3 months on treatment. We used multivariable logistic regression comparing primary versus secondary failure for achievement of CDAI ≤10 (primary outcome) and minimal clinically important differences (secondary outcome) at 6 months after switch., Results: Of the 462 patients included, 64.3% and 35.7% stopped the first TNFi because of a primary and secondary failure, respectively. Patients with primary failure had a more severe disease (CDAI mean, 26.39 vs. 21.61; p < 0.001). The likelihood of achieving CDAI ≤10 (odds ratio, 4.367; 95% confidence interval, 2.428-7.856) and minimal clinically important difference (odds ratio, 2.851; 95% confidence interval, 1.619-5.020) was significantly higher for secondary than primary failure regardless of choice of a second agent., Conclusion: Patients with rheumatoid arthritis with secondary failure to a first TNFi responded better to a second biologic agent, regardless of the choice of biologic., Competing Interests: L.B. has received sources of funding for research from Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, and Gilead; has a consulting agreement/is a member of the advisory board for Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Gilead, Fresenius Kabi, and Teva; and received speaker honoraria agreements for Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Fresenius Kabi, and Teva. M.M. has a faculty position (status) at the University of Toronto with no conflict of interest. G.R. is consultant to Corrona Research Foundation and CorEvitas, LLC. J.M.K. has no conflicts to report. The Corrona Research Foundation is a not-for profit 501(c)3 foundation. K.K. works at UMass Lowell and has a contract with Corrona Research Foundation. E.K. has received sources of funding for research from Amgen, Merck, and Pfizer; has a consulting agreement/is a member of an advisory board for AbbVie, Amgen, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc., Janssen Inc., Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, and Samsung Bioepsis; and received speaker honoraria agreements for Amgen, AbbVie, Celltrion, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sandoz, and Sanofi Genzyme., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To compare a treat-to-target (T2T) approach and routine care (RC) in adults with active to severely active rheumatoid arthritis (RA) initiating subcutaneous abatacept., Methods: A 12-month cluster-randomized trial in active RA patients treated with abatacept was conducted. Physicians were randomized to RC or T2T with a primary endpoint of achieving sustained Clinical Disease Activity Index (CDAI) low disease activity (LDA) at two consecutive assessments approximately 3 months apart. Additional outcomes included Simple Disease Activity Index (SDAI), Disease Activity Score 28-CRP (DAS28-CRP), Routine Assessment of Patient Index Data 3 (RAPID3), and the Health Assessment Questionnaire-Disability Index (HAQ-DI). Time to achieve therapeutic endpoints was assessed with survival analysis., Results: Among the 284 enrolled patients, 130 were in the T2T group and 154 in RC. Primary endpoint was achieved by 36.9% and 40.3% of patients in T2T and RC groups, respectively. No significant between-group differences were observed in the odds of achieving secondary outcomes, except for a higher likelihood of CDAI LDA in the T2T group vs. RC (odds ratio [95% confidence interval]: 1.33 [1.03-1.71], p = 0.0263). Compared with RC, patients in the T2T group achieved SDAI remission significantly faster (Kaplan-Meier-estimated mean [standard error]: 14.0 [0.6] vs. 19.3 [0.8] months, p = 0.0428) with a trend toward faster achievement of CDAI LDA/remission, DAS28-CRP remission, and HAQ-DI minimum clinically important difference., Conclusions: Patients managed per T2T and those under RC experienced significant improvements in RA disease activity at 12 months of abatacept treatment. T2T was associated with higher odds of CDAI LDA and a shorter time to achieving therapeutic endpoints., Trial Registration: Name of the registry: ClinicalTrials.gov., Trial Registrations: NCT03274141 . Date of registration: September 6, 2017., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To characterize the long-term incidence of infection in patients with rheumatoid arthritis (RA) treated with subcutaneous golimumab (GOL) in Canadian routine care, assess the effect of infections on GOL retention, and explore factors associated with infection incidence., Methods: Patients with RA enrolled in the Biologic Treatment Registry Across Canada (BioTRAC) initiating GOL treatment were included. The incidence density rates (IDRs) of total infection (TI), serious infection (SI), and nonserious infection (NSI) were calculated for the overall follow-up (90 months) and by 6-month intervals. Determinants of infection over time or within the first 6 months were explored using generalized estimating equation models and logistic regression, respectively., Results: Five hundred thirty patients were included; mean baseline age was 57.7 years and RA duration was 8.0 years. Over an average follow-up of 27.0 months, the IDR for TIs was 35.1 events per 100 person-years (PYs), the majority occurring during the first 6 months; IDRs for NSIs and SIs were 32.9 and 2.2 events per 100 PYs, respectively. No predictors were identified for infection incidence within 6 months. Comorbid pulmonary disease was associated with significantly higher odds of TIs and NSIs over time, whereas higher age and high corticosteroid (CS) dose (> 5 mg/day) predicted higher odds of SIs. Incidence of SIs, but not NSIs, was associated with significantly higher odds of GOL discontinuation., Conclusion: Long-term GOL treatment was associated with relatively low infection rates, most being nonserious and occurring during the first 6 months. Pulmonary disease, higher age, and high CS dose were identified as significant predictors of infections. SIs, but not NSIs, predicted higher odds of GOL discontinuation. (ClinicalTrials.gov: NCT00741793)., (Copyright © 2023 by the Journal of Rheumatology.)

Purpose: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: To (i) determine whether sustained disease activity states, as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), impact function, and (ii) evaluate characteristics predicting sustained low functional impairment in a prospective axial spondyloarthritis (axSpA) cohort., Methods: Biologic Treatment Registry Across Canada (BioTRAC) was a multi-center, prospective registry that collected real-world data on axSpA patients receiving infliximab or golimumab between 2006 and 2017. Generalized estimating equations (GEE) were used to test baseline characteristics, treatment, and duration (at 6 and 12 months vs. only at 6 or 12 months vs. neither) of low BASDAI (< 3), ASDAS-inactive disease (ID)(< 1.3), and ASDAS-low disease activity (LDA) in predicting sustained low Bath Ankylosing Spondylitis Functional Index (BASFI)(< 3) between 12 and 18 months. The adjusted impact of achieving low disease state at 6 and/or 12 months on BASFI at 18 months was analyzed by generalized linear models., Results: Eight hundred ten patients were enrolled. 33.7%, 13.4%, and 24.7% achieved sustained low BASDAI, ASDAS-ID, and ASDAS-LDA, respectively. In univariable GEE of baseline variables, age and baseline BASDAI, BASFI, and ASDAS significantly predicted sustained low BASFI. In multivariable GEE, sustained low BASDAI (p < 0.001), low BASDAI only at 6 or 12 months (p = 0.001), and baseline BASFI (p < 0.001) were the only predictors of sustained low BASFI. Sustained ASDAS-ID (p = 0.040) and ASDAS-LDA (p < 0.001) were also predictors when forced into the model. Similar results were obtained when evaluating the BASFI score at 18 months., Conclusion: Sustained BASDAI < 3 may be a valid and feasible target for a treat-to-target strategy in axSpA having function as treatment goal., (© 2023. The Author(s).)

A persistent rise in the costs of construction materials has led to the need to address this problem in line with the Sustainable Development Goals. This research employed vegetal soft and rigid fibers in a screed mortar to produce a sustainable fabric-cement matrix. Four different vegetal-dried fibers (hemp, flax, miscanthus, and bamboo) with dosages of 0.4, 0.6, 0.8, 1.2, 2, and 4 kg/m 3 were used. Laboratory investigations were slump test, bulk density, air occluded, shrinkage, and mechanical strength. Scanning Electron Microscope (SEM) assessments were performed and analyzed on the natural fibers and the screed formulation. The results highlight that fiber dosages significantly influence the above-mentioned properties.

Objective: Adults with rheumatoid arthritis (RA) are at a higher risk for infections, including influenza and related complications. We identified influenza vaccination coverage in adults newly diagnosed with RA and examined sociodemographic RA characteristics and attitudes associated with vaccination., Methods: We used data from patients enrolled in the Canadian Early Arthritis Cohort between September 2017 and February 2021. At enrollment, participants reported their vaccination status in the previous year and completed the Beliefs About Medicines Questionnaire (BMQ). Clinical data were obtained from medical records. Logistic regression was used to identify predictors of vaccination in the year after RA diagnosis., Results: The baseline analytic sample of 431 patients were mostly White (80%) women (67%) with a mean age of 56 (SD 14) years. Prediagnosis, influenza vaccine coverage was 38%, increasing to 46% post diagnosis in the longitudinal sample (n = 229). Participants with previous influenza vaccination (odds ratio [OR] 15.33; 95% confidence interval [CI] 6.37-36.90), on biologics or JAKs (OR 5.42; 95% CI 1.72-17.03), and with a higher change in BMQ Necessity-Concerns Differential scores (OR 1.08; 95% CI 1.02-1.15) had greater odds, whereas women (OR 0.32; 95% CI 0.14-0.71), participants with a non-White racial background (OR 0.13; 95% CI 0.04-0.51), and participants currently smoking (OR 0.09; 95% CI 0.02-0.37) had lower odds of influenza vaccine coverage., Conclusion: Influenza vaccination coverage in patients with early RA remains below national targets in adults living with a chronic condition. Discussing vaccine history and medication attitudes at initial clinic visits with new patients with RA may enhance vaccine acceptance and uptake., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To evaluate the effect of tofacitinib (TOF) on American College of Rheumatology (ACR) response criteria components in patients with rheumatoid arthritis (RA)., Methods: This post hoc analysis pooled data from RA phase III randomized controlled trials (RCTs) assessing TOF 5 or 10 mg BID, adalimumab (ADA), or placebo, with conventional synthetic disease-modifying antirheumatic drugs, and a phase IIIb/IV RCT assessing TOF 5 mg BID monotherapy, TOF 5 mg BID with methotrexate (MTX), or ADA with MTX. Outcomes included proportions of patients achieving ACR20/50/70 responses and ≥ 20/50/70% improvement rates in ACR components at week 2 and months 1, 3, and 6; and mean percent improvement in ACR components and Clinical or Simplified Disease Activity Index (CDAI or SDAI) low disease activity or remission rates, at month 3, for ACR20/50/70 responders., Results: Across treatment groups, ≥ 20/50/70% improvement rates were numerically higher for most physician- vs patient-reported measures. In phase III RCTs, at earlier timepoints, ≥ 50/70% improvements in patient global assessment of disease activity, pain, and physician global assessment were similar. Among ACR20 responders receiving TOF, mean percent improvements for tender and swollen joint counts were > 70% at month 3. CDAI/SDAI remission was achieved at month 3 by 27.8-45.0% of ACR70 responders receiving TOF., Conclusion: Among ACR20 responders treated with TOF, physician-reported components particularly exceeded 20% response improvement. At month 3, disease state generally did not corroborate ACR70 response criteria. Divergences between physician- and patient-reported measures highlight the importance of identifying appropriate patient-reported outcome targets to manage RA symptoms in clinical practice. (ClinicalTrials.gov: NCT00847613/NCT00856544/NCT00853385/NCT02187055)., (Copyright © 2022 by the Journal of Rheumatology.)

Objective: COMPLETE-PsA was an observational study of biologic-naïve Canadian adults with active psoriatic arthritis (PsA) treated with adalimumab (ADA) or a nonbiologic disease-modifying antirheumatic drug (nbDMARD) regimen, after inadequate response/intolerance to a current nbDMARD treatment regimen. The aim of this analysis was to assess the 12-month effectiveness of ADA vs nbDMARDs., Methods: Patients enrolled between March 2012 and November 2017 were included. The following clinical variables and patient-reported outcomes were collected/calculated per routine care: Disease Activity Index for Psoriatic Arthritis in 28 joints (DAPSA28), Disease Activity Score in 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein, physician global assessment (PGA), patient global assessment (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), 12-item Short Form Health Survey, enthesitis, dactylitis, body surface area (BSA), and time to achieving American College of Rheumatology (ACR) 50, ACR70, and modified minimal disease activity (mMDA)., Results: Two hundred and seventy-seven ADA-treated and 148 nbDMARD-treated patients were included. At baseline, ADA-treated patients were less likely to be employed, had longer morning stiffness, higher DAPSA28, DAS28, PGA, PtGA, pain, and HAQ-DI, and lower prevalence of dactylitis (all P < 0.05). ADA-treated patients showed lower baseline-adjusted DAPSA28 (16.5 vs 26.6), DAS28 (2.8 vs 3.9), PGA (25.3 vs 37.1), and ESR (10.4 vs 15.0 mm/h) after 3 months compared to nbDMARD-treated patients, with observed improvements maintained to month 12. Time to achievement of ACR50, ACR70, and mMDA was significantly shorter ( P < 0.001) among ADA-treated patients, with the likelihood of having dactylitis (odds ratio [OR] 0.4, 95% CI 0.2-0.6) and BSA< 3% (OR 2.7, 95% CI 1.5-5.0) significantly lower and higher, respectively. Switching to another biologic was less likely in ADA-treated vs nbDMARD-treated patients (hazard ratio 0.3, 95% CI 0.2-0.5)., Conclusion: In a real-world Canadian population of patients with PsA, ADA was more effective than nbDMARDs at reducing disease activity and the severity of skin involvement, and demonstrated higher retention. [ClinicalTrials.gov: NCT01559038]., (© 2022 by the Journal of Rheumatology.)

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This post hoc analysis assessed frequency or duration of early select non-serious adverse events (AEs; excluding infections), and their impact on treatment discontinuation, in patients with RA or PsA treated with tofacitinib 5 or 10 mg twice daily, or placebo., Methods: Data were pooled from five phase 3 and one phase 3b/4 studies in patients with moderate-to-severe RA, and two phase 3 studies in patients with active PsA. Select all-causality, non-serious AEs, reported to month 3 (placebo-controlled period), were headache, diarrhea, nausea, vomiting, and gastric discomfort (including dyspepsia, gastritis, epigastric discomfort, and abdominal discomfort or pain); incidence rates (unique patients with events per 100 patient-years of follow-up), duration of, and discontinuations due to these non-serious AEs were reported., Results: We analyzed 3871 and 710 patients with RA and PsA, respectively. Incidence of non-serious AEs to month 3 was generally similar with tofacitinib and placebo. The most frequent non-serious AEs were headache and diarrhea with tofacitinib, and dyspepsia, nausea, and headache with placebo. Most events were mild or moderate in severity, lasting ≤ 4 weeks. Permanent discontinuations due to non-serious AEs were not observed in patients with PsA, and were < 1.0% in patients with RA across treatment groups. The most frequent cause of temporary discontinuation across all groups was gastric discomfort (0.3-0.8%)., Conclusions: Non-serious AE incidence was generally similar in patients with RA or PsA receiving tofacitinib or placebo. Most events were mild or moderate and generally resolved within 4 weeks., Trial Registration: ClinicalTrials.gov identifiers: NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01877668; NCT01882439; NCT02187055., (© 2021. The Author(s).)

Objective: Evaluate the effect of upadacitinib on pain outcomes in patients with active psoriatic arthritis (PsA) or ankylosing spondylitis (AS) across 3 randomised trials (SELECT-PsA 1 and 2 for PsA; SELECT-AXIS 1 for AS)., Methods: Patients were randomised to upadacitinib 15 mg once daily or placebo (all 3 studies), or adalimumab 40 mg every other week (SELECT-PsA 1 only). Pain outcomes included proportion of patients achieving ≥30%, ≥50% and ≥70% reduction from baseline in patient global assessment of pain and other end points., Results: A higher proportion of patients receiving upadacitinib versus placebo achieved ≥30%, ≥50% and ≥70% reduction in pain end points as early as week 2; these improvements with upadacitinib were generally sustained or increased through year 1 (PsA 1/2 studies: 64%/48%, 58%/42% and 38%/22%, respectively; SELECT-AXIS 1 study: 76%, 72% and 54%). Results were similar with adalimumab in PsA 1 (59%, 49% and 32%). Patients who switched from placebo to upadacitinib 15 mg were able to reach a similar level of improvement as the continuous upadacitinib groups by year 1 (PsA 1/2 studies: 46%-60%, 35%-49% and 15%-34%; AS study: 83%, 72% and 46%). Results were similar with other pain end points., Conclusion: Rapid and sustained improvements in pain outcomes across several end points were consistently shown with upadacitinib over 1 year in patients with active PsA or AS who had either inadequate response to prior non-biologic or biologic disease-modifying antirheumatic drugs (PsA studies) or were biologic-naïve with inadequate response to non-steroidal anti-inflammatory drugs (AS study)., Competing Interests: Competing interests: IBM has received research grants, and/or consulting fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers, Celgene, Janssen, Leo, Lilly, Novartis, Pfizer and UCB. AJKO has served as a consultant and/or on advisory boards for AbbVie, BMS, Gilead, Roche, Janssen, Lilly, Novartis, Paradigm, Pfizer and UCB. PJM has received research grants, consulting fees and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers, Celgene, Galapagos, Genentech, Gilead, GlaxoSmithKline, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, Sun Pharma and UCB. WT has served on advisory boards or as a consultant or received speaker fees from AbbVie, Amgen, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer and UCB. XB has received honoraria and consultancy fees from AbbVie, Amgen, BMS, Chugai, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz and UCB. KdV has received grant/research support from Celgene and Galapagos; consultancy fees from Celgene, Eli Lilly, Galapagos, Novartis and UCB; and speaker fees from Celgene, Eli Lilly, Galapagos, Novartis and UCB. LB has received grant/research support from AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Sanofi and UCB; received speaker fees from AbbVie, Amgen, BMS, Celgene, Fresenius Kabi, Janssen, Lilly, Merck, Novartis, Pfizer, Sanofi, Teva and UCB; and served as an officer or board member for AbbVie, Amgen, BMS, Celgene, Fresenius Kabi, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Sanofi and UCB. RL, AM, DF, TG, PZ, CS, KK and I-HS are full-time, salaried employees of AbbVie and may own AbbVie stock or stock options. AD has received research grants, consultancy fees, speaker fees and other support (medical writing support) from Novartis and Pfizer; research grants, consultancy fees and other support (medical writing support) from AbbVie, Eli Lilly and UCB Pharma; research grants and consultancy fees from GlaxoSmithKline; consultancy fees and other support (medical writing support) from Galapagos and Janssen; consultancy fees from Boehringer Ingelheim and Celgene; and other support (medical writing support) from Amgen., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the long-term safety and efficacy of the Janus kinase inhibitor upadacitinib versus adalimumab over 3 years in the ongoing long-term extension (LTE) of SELECT-COMPARE, a randomised controlled phase 3 trial of patients with active rheumatoid arthritis and inadequate response to methotrexate (MTX)., Methods: Patients on stable background MTX were randomised 2:2:1 to upadacitinib 15 mg, placebo or adalimumab 40 mg. Patients with an insufficient response were switched by week 26 from placebo to upadacitinib, upadacitinib to adalimumab or adalimumab to upadacitinib. Patients who completed the 48-week double-blind period could enter an LTE for up to 10 years. Safety and efficacy results were analysed here through 3 years. Treatment-emergent adverse events (AEs) were summarised based on exposure to upadacitinib and adalimumab. Efficacy was analysed by original randomised groups (non-responder imputation), as well as separately by treatment sequence (as observed)., Results: Rates of several AEs were generally comparable between upadacitinib and adalimumab, including AEs leading to discontinuation, serious infections and serious AEs, malignancies, major adverse cardiac events, venous thromboembolism and deaths. Consistent with earlier results, herpes zoster, lymphopaenia, hepatic disorder and CPK elevation were reported at higher rates with upadacitinib versus adalimumab. In terms of efficacy, upadacitinib continued to show numerically better clinical responses than adalimumab over 3 years across all endpoints, including low disease activity and remission., Conclusion: The safety profile of UPA 15 mg was consistent with previous study-specific and integrated safety reports. Higher levels of clinical response continued to be observed with upadacitinib versus adalimumab through 3 years of treatment., Competing Interests: Competing interests: RF: Research grants and consulting fees from AbbVie, Amgen, Astra-Zeneca, Biosplice, BMS, Flexion, Galvani, Genentech, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, UCB, Viela, Vorso. EM: Research grants and consulting fees from AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz, Amgen, AstraZeneca, GSK, Janssen, Novartis. LB: speaker, consulting fees and research support from Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Sanofi, Eli Lilly, Novartis, Teva, Gilead, Fresenius Kabi. CGP: Employee and shareholder: Spire Sciences; speaker: Amgen, Bristol-Myers Squibb; consultant: Aclaris, Centrexion, Daiichi-Sankyo, EMD Serono, Five Prime, Flexion Therapeutics, Genentech, Gilead, GlaxoSmithKline, Istresso, Eli Lilly, Myriad Genetics, Novartis, Roche, SetPoint, Sorrento, UCB. PD: Speaker fees from BMS, Sanofi, Eli Lilly, Celltrion. YT: speaker and/or received honoraria from Gilead, AbbVie, Boehringer Ingelheim, Eli Lilly, Mitsubishi-Tanabe, Chugai, Amgen, YL Biologics, Eisai, Astellas, Bristol-Myers, AstraZeneca; research grants from Asahi-Kasei, AbbVie, Chugai, Mitsubishi Tanabe, Eisai, Takeda, Corrona, Daiichi-Sankyo, Kowa, Boehringer Ingelheim. JS: Speaker, research grants and consulting fees from AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen. NK, XB, YL, and I-HS: employees of AbbVie and may hold stock or options., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: This study aims to determine whether patients with active rheumatoid arthritis (RA), either starting on or changing biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs), demonstrate better self-management safety skills three months after receiving a multidisciplinary educational intervention compared to patients receiving usual care., Patients and Methods: Between October 2015 and October 2018 , this open-label, randomized-controlled trial included a total of 107 RA patients (27 males, 80 females; mean age: 60.2±10.4 years; range, 54 to 71 years) who were on treatment or in whom treatment was changed with a biological or targeted synthetic DMARD. The patients were randomized into two groups: Group 1 (n=57) received additional intervention with educational DVD and one teleconference session and Group 2 (n=55) received usual care and were offered the intervention at three months. All patients underwent a final visit at six months. At each visit, the patients completed the BioSecure questionnaire measuring the self-care safety skills, a behavioral intention questionnaire, and the Beliefs about Medicines Questionnaire (BMQ)., Results: No significant difference was observed in the Biosecure score at three months between the two groups (p=0.08). After pooling the first three-month data in Group 1 and the last three-month data in Group 2, the mean score of the BioSecure questionnaire increased to 7.10±0.92 in the group receiving educational intervention (p<0.0001). This increase was maintained at six months in Group 2 (p=0.88). The rate of appropriate behavioral intention increased over time (76% at baseline and 85% at six months for both groups). There was no significant change in the BMQ (p=0.44 to 0.84)., Conclusion: The development of an educational DVD followed by a teleconference seem to improve self-care safety skills of the patients in practical situations., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2022, Turkish League Against Rheumatism.)

In Canada and other countries, osteoporosis is monitored as part of chronic disease population surveillance programs. Although fractures are the principal manifestation of osteoporosis, very few algorithms are available to identify individuals at high risk of osteoporotic fractures in current surveillance systems. The objective of this study was to derive and validate predictive models to accurately identify individuals at high risk of osteoporotic fracture using information available in healthcare administrative data. More than 270,000 men and women aged ≥66 years were randomly selected from the Quebec Integrated Chronic Disease Surveillance System. Selected individuals were followed between fiscal years 2006-2007 and 2015-2016. Models were constructed for prediction of hip/femur and major osteoporotic fractures for follow-up periods of 5 and 10 years. A total of 62 potential predictors measurable in healthcare administrative databases were identified. Predictor selection was performed using a manual backward algorithm. The predictive performance of the final models was assessed using measures of discrimination, calibration, and overall performance. Between 20 and 25 predictors were retained in the final prediction models (eg, age, sex, social deprivation index, most of the major and minor risk factors for osteoporosis, diabetes, Parkinson's disease, cognitive impairment, anemia, anxio-depressive disorders). Discrimination of the final models was higher for the prediction of hip/femur fracture than major osteoporotic fracture and higher for prediction for a 5-year than a 10-year period (hip/femur fracture for 5 years: c-index = 0.77; major osteoporotic fracture for 5 years: c-index = 0.71; hip/femur fracture for 10 years: c-index = 0.73; major osteoporotic fracture for 10 years: c-index = 0.68). The predicted probabilities globally agreed with the observed probabilities. In conclusion, the derived models had adequate predictive performance in internal validation. As a final step, these models should be validated in an external cohort and used to develop indicators for surveillance of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Background: Precision medicine, as a personalized medicine approach based on biomarkers, is a booming field. In general, physicians and patients have a positive attitude toward precision medicine, but their knowledge and experience are limited. In this study, we aimed at assessing the expectations and educational needs for precision medicine among rheumatologists, rheumatology fellows and patients with rheumatic diseases in Canada., Methods: We conducted two anonymous online surveys between June and August 2018, one with rheumatologists and fellows and one with patients assessing precision medicine expectations and educational needs. Descriptive statistics were performed., Results: 45 rheumatologists, 6 fellows and 277 patients answered the survey. 78% of rheumatologists and fellows and 97.1% of patients would like to receive training on precision medicine. Most rheumatologists and fellows agreed that precision medicine tests are relevant to medical practice (73.5%) with benefits such as helping to determine prognosis (58.9%), diagnosis (79.4%) and avoid treatment toxicity (61.8%). They are less convinced of their usefulness in helping to choose the most effective treatment and to improve patient adherence (23.5%). Most patients were eager to take precision medicine tests that could predict disease prognosis (92.4%), treatment response (98.1%) or drug toxicity (93.4%), but they feared potential negative impacts like loss of insurability (62.2%) and high cost of the test (57.5%)., Conclusions: Our study showed that rheumatologists and patients in Canada are overall interested in getting additional precision medicine education. Indeed, while convinced of the potential benefits of precision medicine tests, most physicians don't feel confident in their abilities and consider their training insufficient to incorporate them into clinical practice., (© 2021. The Author(s).)

Objective: The objective of this study was to compare the incidence rate of nonvertebral osteoporotic fractures (NVFs) in patients with rheumatoid arthritis (RA) initiating one of the nine biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs)., Methods: We analyzed claims data from Optum (2008 to March 2019), Medicare, and MarketScan (2008-2017) to identify adults with RA who newly initiated b/tsDMARDs. Adalimumab was the most frequently used and was thus selected as a reference. The primary outcome was a composite of incident NVFs, including hip, humerus, pelvis, and wrist fractures, based on validated algorithms. We adjusted for greater than 70 potential confounders in each database through propensity score-based inverse probability treatment weighting. Follow-up time started the day after cohort entry until the first occurrence of one of the following: outcome, treatment discontinuation, switching, nursing home admission, death, disenrollment, or end of study period. For each drug comparison, weighted Cox proportional hazards models estimated the hazard ratios (HRs) and 95% confidence intervals (CIs). Secondary analyses were conducted in patients switching from a tumor necrosis factor inhibitor to a different b/tsDMARD., Results: A total of 134,693 b/tsDMARD initiators were identified across three databases. The adjusted HRs showed similar risk of composite NVFs in all b/tsDMARD exposures compared with adalimumab: abatacept, HR 1.03 (95% CI 0.82-1.30); certolizumab, HR 1.08 (95% CI 0.79-1.49); etanercept, HR 1.12 (95% CI 0.89-1.40); golimumab, HR 0.91 (95% CI 0.59-1.39); infliximab, HR 1.03 (95% CI 0.84-1.28); rituximab, HR 1.07 (95% CI 0.74-1.55); tocilizumab, HR 1.24 (95% CI 0.71-2.17); and tofacitinib, HR 1.07 (95% CI 0.69-1.64). Secondary analyses showed similar results., Conclusion: This multidatabase cohort study found no differences in the risk of NVFs across individual b/tsDMARDs for RA, which provides reassurance to physicians prescribing b/tsDMARDs, especially to patients at high risk of developing NVFs., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Purpose: Accurately identifying patients with psoriasis (PsO) is crucial for generating real-world evidence on PsO disease course and treatment utilization., Methods: We developed nine claims-based algorithms for PsO using a combination of the International Classification of Diseases (ICD)-9 codes, specialist visit, and medication dispensing using Medicare linked to electronic health records data (2013-2014) in two healthcare provider networks in Boston, Massachusetts. We calculated positive predictive value (PPV) and 95% confidence interval (CI) for each algorithm using the treating physician's diagnosis of PsO via chart review as the gold standard. Among the confirmed PsO cases, we assessed their PsO disease activity., Results: The nine claims-based algorithms identified 990 unique patient records. Of those, 918 (92.7%) with adequate information were reviewed. The PPV of the algorithms ranged from 65.1 to 82.9%. An algorithm defined as ≥1 ICD-9 diagnosis code for PsO and ≥1 prescription claim for topical vitamin D agents showed the highest PPV (82.9%). The PPV of the algorithm requiring ≥2 ICD-9 diagnosis codes and ≥1 prescription claim for PsO treatment excluding topical steroids was 81.1% but higher (82.5%) when ≥1 diagnosis was from a dermatologist. Among 411 PsO patients with adequate information on PsO disease activity in EHRs, 1.5-5.8% had no disease activity, 31.3-36.8% mild, and 26.9-35.1% moderate-to-severe across the algorithms., Conclusions: Claims-based algorithms based on a combination of PsO diagnosis codes and dispensing for PsO-specific treatments had a moderate-to-high PPV. These algorithms can serve as a useful tool to identify patients with PsO in future real-world data pharmacoepidemiologic studies., (© 2021 John Wiley & Sons Ltd.)

The myeloid inhibitory receptor CLEC12A negatively regulates inflammation. Reduced CLEC12A expression enhances inflammation in CLEC12A knock-out mice with collagen antibody-induced arthritis. Moreover, CLEC12A internalisation augments human neutrophil activation. We thus postulated that CLEC12A expression on circulating myeloid cells of rheumatoid arthritis patients is associated with disease manifestations. Cell-surface, CLEC12A receptor expression was determined on circulating neutrophils and monocytes of eRA patients and of healthy donors. Generalized estimating equations model, Student's t-test and Spearman's correlations were performed to compare CLEC12A expression between groups and test its association with disease activity and clinical parameters. Plasma cytokines were measured by multiplex immunoassay. Patients with reduced neutrophil or monocyte CLEC12A expression at baseline and at 3 months have an increased simple disease activity index. Low baseline CLEC12A expression also correlates with a higher SDAI at 6 months. In contrast, positive correlations were observed between baseline CLEC12A expression and several cytokines. Moreover, neutrophil and monocyte CLEC12A expression is significantly higher in early rheumatoid arthritis patients at baseline than healthy controls. Circulating neutrophil and monocyte CLEC12A expression correlates with disease activity at baseline and is predictive of SDAI at later stages of the disease indicative of a regulatory role for CLEC12A in RA.

Objectives: To evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy., Methods: SELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts ('non-responders') and at week 26 based on Clinical Disease Activity Index (CDAI) >10 ('incomplete-responders') without washout., Results: A total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups., Conclusions: These observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout., Competing Interests: Competing interests: RMF has received grant/research support from AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD-Serono, Genentech, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Roche, Sanofi-Aventis, UCB and Viela and is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis and UCB. RB has received grants/research support from AbbVie, MSD and Roche and had consultation fees/participation in company-sponsored speaker’s bureau from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, and Roche. SH has received research grants and consultancy fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer and UCB. GTDT has received a research grant from AbbVie and consulting fees from Amgen. FEVdB has received speaker and/or consultancy fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. CZ has received grants/research support from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer and Sanofi. LB has received grant/research support from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis and UCB and is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis and UCB. JE, YL, YS, RD and I-HS are full-time employees of AbbVie and may hold AbbVie stock or stock options., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA)., Methods: Treatment-emergent adverse events (TEAEs) and laboratory data from five randomised, placebo- or active-controlled phase III trials of upadacitinib for patients with RA were analysed and summarised. Exposure-adjusted event rates are shown for placebo (three trials; 12/14 weeks), methotrexate (two trials; mean exposure: 36 weeks), adalimumab (one trial; mean exposure: 42 weeks), upadacitinib 15 mg (five trials; mean exposure: 53 weeks) and upadacitinib 30 mg (four trials; mean exposure: 59 weeks)., Results: 3834 patients received one or more doses of upadacitinib 15 mg (n=2630) or 30 mg (n=1204), for a total of 4020.1 patient-years of exposure. Upper respiratory tract infection, nasopharyngitis and urinary tract infection were the most commonly reported TEAEs with upadacitinib. Rates of serious infection were similar between upadacitinib 15 mg and adalimumab but higher compared with methotrexate. Rates of herpes zoster and creatine phosphokinase (CPK) elevations were higher in both upadacitinib groups versus methotrexate and adalimumab, and rates of gastrointestinal perforations were higher with upadacitinib 30 mg. Rates of deaths, malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs) were similar across treatment groups., Conclusion: In the phase III clinical programme for RA, patients receiving upadacitinib had an increased risk of herpes zoster and CPK elevation versus adalimumab. Rates of malignancies, MACEs and VTEs were similar among patients receiving upadacitinib, methotrexate or adalimumab., Trial Registration Numbers: SELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847., Competing Interests: Competing interests: SBC received grants and consultation fees from Amgen, AbbVie, Boehringer Ingelheim, Gilead, Pfizer, Roche and Sandoz. RFvV received grants from AbbVie, Arthrogen, BMS, GSK, Lilly, Pfizer and UCB and personal fees from AbbVie, AstraZeneca, Biotest, BMS, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche and UCB. KLW received consulting fees and research grants from AbbVie, BMS, Lilly, Pfizer, Roche and UCB. CAFZ received research grants from Amgen, GSK, Lilly, Merck, Novartis, Pfizer, Sanofi-Aventis, Servier and Roche, participated on advisory boards and speaker’s bureau for Merck, Pfizer, and Sanofi-Aventis and served as a consultant for Pfizer. YT received speaking fees and/or honoraria from AbbVie, Asahi-Kasei, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Gilead, GSK, Janssen, Lilly, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi and YL Biologics and received research grants from Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Takeda and UCB. LB received speaking fees, consulting fees and research grants from AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB. YZ, NK, BH and JVE are full-time employees of AbbVie and may hold AbbVie stock or stock options. GRB received speaking or consulting fees from AbbVie, Gilead, Janssen, Lilly, MSD, Pfizer, Roche and UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 <1 year) enrolled in the Canadian Early Arthritis Cohort who initiated disease-modifying antirheumatic drugs and had completed HAQ data at baseline and 1 year were included in the study. Discrete-time proportional hazards models were used to estimate crude and multi-adjusted associations of baseline HAQ and HAQ at 1 year with all-cause mortality in each year of follow-up., Results: A total of 1,724 patients with early RA were included. The mean age was 55 years, and 72% were women. Over 10 years, 62 deaths (3.6%) were recorded. Deceased patients had higher HAQ scores at baseline (mean ± SD 1.2 ± 0.7) and at 1 year (0.9 ± 0.7) than living patients (1.0 ± 0.7 and 0.5 ± 0.6, respectively; P < 0.001). Disease Activity Score in 28 joints (DAS28) was higher in deceased versus living patients at baseline (mean ± SD 5.4 ± 1.3 versus 4.9 ± 1.4) and at 1 year (mean ± SD 3.6 ± 1.4 versus 2.8 ± 1.4) (P < 0.001). Older age, male sex, lower education level, smoking, more comorbidities, higher baseline DAS28, and glucocorticoid use were associated with mortality. Contrary to HAQ score at baseline, the association between all-cause mortality and HAQ score at 1 year remained significant even after adjustment for confounders. For baseline HAQ score, the unadjusted hazard ratio (HR) was 1.46 (95% confidence interval [95% CI] 1.02-2.09), and the adjusted HR was 1.25 (95% CI 0.81-1.94). For HAQ score at 1 year, the unadjusted HR was 2.58 (95% CI 1.78-3.72), and the adjusted HR was 1.75 (95% CI 1.10-2.77)., Conclusion: Our findings indicate that higher HAQ score and DAS28 at 1 year are significantly associated with all-cause mortality in a large early RA cohort., (© 2020, American College of Rheumatology.)

Objective: To examine the relationship between disease activity and fatigue over time in early rheumatoid arthritis (RA)., Methods: Data were from patients with early RA (duration of symptoms ≤12 months) enrolled in the Canadian Early Arthritis Cohort (CATCH). Patients rated their fatigue over the past week using an 11-point numerical rating scale (NRS) for up to 5 years of follow-up. Fatigue severity was classified as low (≤2), moderate (>2 but <5), or high (≥5). Differences in fatigue ratings in patients who achieved a low disease state (Disease Activity Score in 28 joints [DAS28] <3.2) and those who did not within 3-months of cohort entry were compared., Results: Of 1,864 patients included, 88% met RA criteria, and 72% were women. The mean ± SD baseline DAS28 was 4.9 ± 1.5. Nineteen percent of the patients reported moderate baseline fatigue, and 59% reported severe baseline fatigue. Fatigue was correlated with pain and patient global ratings (r = 0.56-0.67, P < 0.001), and was weakly correlated with DAS28, tender joint count, swollen joint count, physician global assessment of disease activity, erythrocyte sedimentation rate, and C-reactive protein level. Patients who reported low fatigue by 3 months had significantly lower fatigue throughout follow-up compared to those who had moderate or high fatigue at 3 months (P < 0.001). Patients who achieved a DAS28 <3.2 within 3 months had significantly lower fatigue ratings (mean ± SD 2.7 ± 2.6) than those with a DAS28 >3.2 (4.6 ± 3.0) (P < 0.001), with improvements in fatigue that persisted through 5 years of follow-up. Maximal improvements in fatigue lagged behind remission by 6 months., Conclusion: Fatigue is common in early RA, and improvements may occur after remission. Early treatment response within 3-months was associated with short-term and long-term benefits in fatigue over time., (© 2020, American College of Rheumatology.)

Objective: The objective of this study was to investigate whether diacerein has comparable efficacy with celecoxib in pain reduction for treatment in symptomatic knee OA patients., Methods: This randomized double-blind multicentre non-inferiority trial evaluated diacerein vs celecoxib treatment in patients with Kellgren-Lawrence grade 2-3 and pain scoring ≥4 (10-cm VAS). Patients were randomized to 6 months of treatment with diacerein 50 mg (n = 187) once daily for 1 month and twice daily thereafter, or celecoxib 200 mg (n = 193) once daily. The primary outcome was the change in WOMAC pain score (0-50 cm) at 6 months, and the secondary outcomes were WOMAC sub-scores, VAS pain score, and the OMERACT-OARSI responder rate., Results: In the per protocol population, the adjusted mean change from baseline in the WOMAC pain score was -11.1 ( 0.9) with diacerein (n = 140) and -11.8 (0.9) with celecoxib (n = 148). The intergroup difference was 0.7 (95% CI: -1.8, 3.2; P = 0.597), meeting the non-inferiority margin. Supportive analysis of the intention-to-treat population gave similar results. Other outcomes showed no significant difference between treatment groups. The incidence of treatment-related adverse events was low and balanced between groups, but a greater incidence of diarrhoea occurred with diacerein (10.2% vs 3.7%). Diarrhoea was considered mild-to-moderate in all but one case with complete resolution., Conclusions: Diacerein was non-inferior to celecoxib in reducing knee OA pain and improving physical function. Diacerein also demonstrated a good safety profile., Trial Registration: A multicentre study on the effect of DIacerein on Structure and Symptoms vs Celecoxib in Osteoarthritis is a National Institutes of Health (NCT02688400) and European Clinical Trial Database (2015-002933-23) registered phase III (Canada) or IV (Europe) study., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Patients with ankylosing spondylitis (AS) are burdened with symptoms impacting work productivity measured by presenteeism, absenteeism, overall work impairment, and activity impairment. Ixekizumab, a high-affinity monoclonal antibody selectively targeting interleukin-17A, has been demonstrated to improve disease signs and symptoms in two phase 3 trials of AS. This study investigated for 52 weeks the effect of ixekizumab treatment on work productivity in patients with active AS., Methods: COAST-V (NCT02696785) and COAST-W (NCT02696798) were phase 3, multicenter, randomized, controlled trials investigating the efficacy of ixekizumab 80 mg every 4 weeks (Q4W) and every 2 weeks (Q2W) in patients with AS naïve to biologic disease-modifying antirheumatic drugs (bDMARDs; COAST-V) or who were inadequate responders or intolerant to tumor necrosis factor inhibitors (TNFi; COAST-W). Work productivity was measured with the Work Productivity and Activity Impairment Questionnaire for Spondyloarthritis at weeks 16 and 52. Absenteeism, presenteeism, and overall work impairment were assessed for patients reporting paid work. Activity impairment was assessed regardless of work status., Results: At baseline, 66.2% (434/656) of patients reported paid work. At week 16, bDMARD-naïve patients treated with both ixekizumab dose regimens and TNFi-experienced patients treated with ixekizumab Q2W reported significant improvements in activity impairment (p < 0.01 and p < 0.05, respectively). TNFi-experienced patients treated with ixekizumab showed significant improvements versus placebo in presenteeism and overall work impairment (p < 0.05); bDMARD-naïve patients had numeric improvements. After week 16, patients initially on placebo switched to ixekizumab and patients already treated with ixekizumab continued treatment. Improvements in work productivity and daily activity were sustained through week 52 for both bDMARD-experienced and -naïve patients., Conclusion: Both bDMARD-naïve and TNFi-experienced patients with AS had greater improvements in work productivity and activity impairment when receiving ixekizumab compared to placebo at week 16. Improvements in work productivity and activity impairment achieved at week 16 were sustained through week 52 with ixekizumab treatment.

Background: The objectives of this study were to describe the profile of ankylosing spondylitis (AS) patients treated with either infliximab (IFX) or subcutaneous golimumab (GLM) treatment in Canadian routine care setting along with assessing long-term effectiveness and safety., Methods: AS patients who were eligible for treatment with IFX or subcutaneous GLM as per their respective Canadian product monographs were enrolled into the BioTRAC registry from 2005 to 2017. The study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed by changes in clinical outcomes and acute phase reactants. Safety was evaluated by assessing the incidence of adverse events (AEs) and drug survival rates., Results: A total of 389 IFX- and 421 GLM-treated patients were enrolled. A significant decrease in disease duration at baseline was observed in the IFX cohort, from a median of 8.0 in 2005-2008 to 1.0 years in 2009-2015 (p < 0.001). A reduction in baseline BASFI score (p = 0.011) and proportion of patients in ASDAS very high disease activity (p = 0.004) was also observed over time. Meanwhile, in the GLM cohort, most disease parameters remained similar from 2010 to 2017. Treatment with both agents significantly improved all disease parameters over time with similar efficacy between the two agents. The incidence of AEs and SAEs were 136 and 131 events/100 PYs and 10.5 and 8.45 events/100 PYs for IFX- and GLM-treated patients, respectively., Conclusion: Both IFX and GLM treatment in AS significantly reduced disease activity in most outcome measures in a similar fashion and were well tolerated in Canadian routine care., Trial Registration: NCT00741793 .

Background: In Canadian medicine faculties, an average of 2.3% of the medical curriculum is dedicated to musculoskeletal problems with a focus on orthopedic conditions. The goal of this descriptive study was to assess the educational preferences in rheumatology of family medicine residents and to identify their preferred methods of learning., Methods: From September 2017 to December 2017, two hundred and thirty-six first- and second-year family medicine residents from Université Laval were asked to complete an electronic anonymous survey assessing their confidence in doing different rheumatology tasks. They were also consulted on their favorite methods of learning and their preferred periods throughout their medical cursus to learn the different skills related to rheumatology., Results: Eighty-five family medicine residents completed the survey. The residents were rather confident when evaluating mono-arthritis but less confident for oligo/polyarthritis and even less confident with connective tissue diseases. The family medicine residents mentioned preferring traditional lecture classes and clinical cases. They wanted to learn the majority of rheumatology education during medical school training. As residents, they wanted only small capsules, seminars, or memory aids. Interestingly, men preferred learning rheumatology skills during the residency, whereas women preferred learning it in medical school., Conclusion: The lack of confidence of family medicine residents when evaluating systemic inflammatory diseases compared to mechanical musculoskeletal problems highlights the importance of rheumatology teaching through general medical training and through family medicine residency. Key Points • Family medicine residents are less confident when evaluating systemic inflammatory diseases than musculoskeletal disorders. • Family medicine residents prefer traditional lecture classes and clinical cases. • Family medicine residents prefer learning rheumatology during medical school training.

Objectives: The objective of this trial was to compare effectiveness of certolizumab pegol added to conventional synthetic DMARDs (csDMARDs) in RA patients, followed by continuing vs discontinuing background csDMARDs after treatment response., Methods: Patients with active RA who had certolizumab pegol added to their existing csDMARD regimen due to inadequate response were eligible. At 3 or 6 months, patients who achieved a change (Δ) in DAS28 of ⩾1.2 were randomized to continue combination therapy (COMBO) or withdraw csDMARD therapy (MONO) (unblinded). The primary outcome was non-inferiority of stopping vs continuing csDMARD(s) in terms of maintaining ΔDAS28 ⩾ 1.2 or achieving DAS28 low disease activity at 18 months (non-inferiority margin: 15 percentile units)., Results: A total of 125 patients were enrolled, 88 randomized to COMBO (n = 43) or MONO (n = 45). No significant differences were observed between groups in baseline age, gender, race, RF status or prior biologics (16% vs 11%). Although the rate of ΔDAS28 ⩾ 1.2 and/or DAS28 low disease activity achievement at 18 months was clinically comparable between the two groups (72% vs 69%), non-inferiority assumptions were not met [absolute risk difference (upper limit of 90% CI): 2.6% (19.1%)]. Similar baseline-adjusted improvements were seen in DAS28 (COMBO vs MONO: -2.3 vs -2.1; P = 0.49) and all endpoints were not statistically different including 59% vs 56% achieved DAS28 low disease activity, 69% vs 59% ΔDAS28 ⩾ 1.2, and 41% each remission., Conclusion: Among RA patients achieving a therapeutic response on combination therapy with certolizumab pegol and csDMARDs, withdrawing csDMARDs was not non-inferior to maintaining csDMARDs but improvements were sustained in both groups at 18 months., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To examine the onset and maintenance of efficacy of subcutaneous tanezumab for pain relief and functional improvement in difficult-to-treat patients with moderate-to-severe osteoarthritis (OA) in a 16-week dose-titration study (NCT02697773)., Methods: Patients were randomized to placebo (placebo group) or tanezumab 2.5 mg at baseline and week 8 (tanezumab 2.5 mg group), or tanezumab 2.5 mg at baseline and tanezumab 5 mg at week 8 (tanezumab 2.5/5 mg group). Analyses included change from baseline in average daily index joint pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and treatment responses (WOMAC Pain improvement criteria and Outcome Measures in Rheumatology-Osteoarthritis Research Society International [OMERACT-OARSI] criteria)., Results: The 696 patients received placebo (n = 232), tanezumab 2.5 mg (n = 231), or tanezumab 2.5/5 mg (n = 233). Average daily index joint pain was statistically significantly improved within the first week (day 3-5) with tanezumab 2.5 mg compared with placebo. On first post-randomization WOMAC measurement (week 2), both tanezumab groups had statistically significant improvements compared with placebo in WOMAC Pain and Physical Function, and more tanezumab-treated patients achieved treatment response criteria (≥30%, ≥50%, or ≥70% reduction in WOMAC Pain or OMERACT-OARSI response). Efficacy was generally maintained throughout the 16-week treatment period., Conclusion: Subcutaneous tanezumab provided statistically significant improvements compared with placebo in average daily index joint pain within the first week and WOMAC Pain and Physical Function (week 2) that were generally maintained throughout the 16-week treatment period. Tanezumab 5 mg provided only modest additional efficacy over tanezumab 2.5 mg., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To describe characteristics, treatment patterns and persistence in patients with RA treated with tofacitinib, an oral Janus kinase inhibitor, in Canadian clinical practice between 1 June 2014 and 31 May 2017., Methods: Data were obtained from the tofacitinib eXel support programme. Baseline demographics and medication history were collected via patient report/special authorization forms; reasons for discontinuation were captured by patient report. Treatment persistence was estimated using Kaplan-Meier methods, with data censored at last follow-up. Cox regression was applied to analyse baseline characteristics associated with treatment discontinuation., Results: The number of patients with RA enrolled from 2014 to 2017 was 4276; tofacitinib utilization increased during that period, as did the proportion of biologic (b) DMARD-naïve patients prescribed tofacitinib. Of patients who initiated tofacitinib, 1226/3678 (33.3%) discontinued, mostly from lack of efficacy (35.7%) and adverse events (26.9%). Persistence was 62.7% and 49.6% after 1 and 2 years of treatment, respectively. Prior bDMARD experience predicted increased tofacitinib discontinuation (vs bDMARD-naïve, P < 0.001). Increased retention was associated with older age (56-65 years and >65 years vs ⩽45 years; P < 0.05), and time since diagnosis of 15 to <20 years (vs <5 years; P < 0.01). In bDMARD-naïve, post-1 bDMARD, post-2 bDMARD and post-⩾3 bDMARD patients, median survival was >730, 613, 667 and 592 days, respectively., Conclusion: Since 2014, tofacitinib use in Canadian patients with RA increased, especially among bDMARD-naïve/post-1 bDMARD patients. Median drug survival was ∼2 years. Likelihood of persistence increased for bDMARD-naïve (vs bDMARD-experienced) patients and those aged ⩾56 (vs ⩽45) years., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)