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

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

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

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

Objective.To evaluate the prevalence and predictive factors of sustained remission in an early rheumatoid arthritis (ERA) population. Predictive factors of sustained remission in ERA are unknown. We hypothesized that a short time to remission is an important predictor of sustained clinical remission.Methods.Patients in the Canadian Early Arthritis Cohort were included. Remission was defined by Boolean-based American College of Rheumatology/European League Against Rheumatism clinical trial and clinical practice definitions and Simplified Disease Activity Index (SDAI). Logistic regression analysis identified predictors of sustained remission and influence of time to remission.Results.Of 1840 patients, 633 (34%) achieved clinical trial remission, 759 (41%) clinical practice remission, and 727 (39%) SDAI remission. Over half of those meeting remission criteria achieved sustained remission based on clinical trial (55%), clinical practice (60%), and/or SDAI (58%). Corticosteroid use and lack of initial disease-modifying antirheumatic drug (DMARD) were associated with decreased probability of sustained remission, while initial combination DMARD increased this probability. Female sex, greater pain, and longer time to first remission made sustained remission less likely.Conclusion.Female sex, greater pain, and lack of initial DMARD therapy reduced the probability of sustained remission. A shorter time to remission is related to sustainability and supports striving for early remission.

The 28-Joint Disease Activity Score (DAS28) using C-reactive protein (CRP) and DAS28 using erythrocyte sedimentation rate (DAS28-ESR) may not be interchangeable. We sought to compare and estimate optimal thresholds for the DA28-CRP for use in early rheumatoid arthritis (ERA).Patients from the Canadian Early Arthritis Cohort with baseline and 12 months' data for both DAS28-ESR and DAS28-CRP were examined for correlations and differences between DAS28-CRP and DAS28-ESR across their range of values. Receiver operating characteristic analysis identified thresholds for DAS28-CRP that best corresponded to established thresholds for the DAS28-ESR using the total sample, then stratified by age and sex. Agreement between DAS28-CRP and DAS28-ESR thresholds was assessed with the kappa statistic.The sample included 995 patients with mean (SD) age of 53.7 (14.5) years, 5.8 (2.9) months of symptom duration and 74% were female. DAS28-CRP and DAS28-ESR scores were highly correlated (r= 0.92, p0.0001), however DAS28-CRP values were consistently lower than DAS28-ESR values. Calculated thresholds for DAS28-CRP were lower with 2.5 for remission, 2.9 for low disease activity, and 4.6 for high disease activity but showed moderate agreement with the DAS28-ESR thresholds (kappa=0.70).In this large sample of ERA patients, newly estimated thresholds for DAS28-CRP were consistently lower than DAS28-ESR thresholds across the spectrum of disease activity. This may have important clinical implications if inflammatory markers are used interchangeably. Additional external validation of our findings is needed.

Objectives: To compare the EULAR and SDAI50 response measures (RMs) and their impact on future response to treatment in patients with early rheumatoid arthritis (ERA). Methods: Biologic naive ERA patients from the Canadian early ArThritis CoHort (CATCH) with complete data at baseline, 3 and 6 months were evaluated. Kappa statistics were used to evaluate the agreement between the EULAR (moderate or good response) and SDAI50 RMs. The RMs at 3 months were also compared for their ability to predict low disease activity state (LDAS) or remission (REM) at 6 months. Results: A total of 1124 patients were evaluated. Of those, 215 (30%) and 294 (45%) patients failed to achieve a EULAR and SDAI50 RMs respectively. There was a good agreement between EULAR and SDAI50 RMs with a Kappa of 0.59 (95% CI 0.53- 0.66). Throughout the range of disease activity, the SDAI50 response was shown to be more stringent than the EULAR response. Multivariable linear regression analysis demonstrated that both RMs at 3 months were associated with LDAS or REM at 6 months and SDAI50 had a more significant impact on the this outcome compared to the EULAR response. Conclusion: There is a good agreement between the EULAR and SDAI50 RMs. Although a minority of patients have discordant RMs at each end of the disease activity spectrum at baseline, the SDAI50 response at 3 month appears to be a more significant predictor of outcomes at 6 months than EULAR response. This article is protected by copyright. All rights reserved.

Objective.To determine the factors most strongly associated with an increase in therapy of early rheumatoid arthritis (ERA).Methods.Data from the Canadian Early Arthritis Cohort (CATCH) were included if the patient had ≥ 2 visits and baseline and 6 months data. A regression analysis was done to determine factors associated with treatment intensification.Results.Of 1145 patients with ERA, 790 met inclusion criteria; mean age was 53.4 years (SD 14.7), mean disease duration 6.1 months (SD 2.8), 75% were female, baseline Disease Activity Score-28 (DAS28) was 4.7 (SD 1.8) and 2.9 (SD 1.8) at 6 months for included patients. Univariate factors for intensifying treatment were physician global assessment (MDGA; OR 7.8 and OR 7.4 at 3 and 6 months, respectively, p < 0.0005), swollen joint count (SJC; OR 4.7 and OR 7.3 at 3 and 6 months, p < 0.0005), and DAS28 (OR 3.0 and OR 4.6 at 3 and 6 months, p < 0.0005). In the regression model only MDGA was strongly associated with treatment intensification (OR 1.5 and OR 1.2 at 3 and 6 months, p < 0.0005); DAS28 was not consistently predictive (OR 1.0, p = 0.987, and OR 1.2, p = 0.023, at 3 and 6 months). DAS28 was the reason for treatment intensification 2.3% of the time, compared to 51.7% for SJC, 49.9% for tender joint count, and 23.8% for MDGA. For the same SJC, larger joint involvement was more likely to influence treatment than small joints at 3 months (OR 1.4, p = 0.027).Conclusion.MDGA was strongly associated with an increase in treatment at 3 and 6 months in ERA, whereas DAS28 was not. Physicians rarely stated that DAS28 was the reason for increasing treatment.