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ObjectivesPatients with rheumatoid arthritis (RA) can test either positive or negative for anti-citrullinated protein antibodies (ACPA), and are thereby ACPA-positive (ACPA+) or ACPA-negative (ACPA–), respectively. Through comprehensive profiling of autoantibodies in serum, we aimed to identify autoantibodies that are differentially abundant between patients with ACPA+ RA and ACPA– RA, and also those that are significantly associated with clinical disease activity.MethodsSerum was collected from patients with ACPA+ RA (n= 32), ACPA– RA (n= 30), and healthy controls (n= 30). Sengenics Immunome™protein microarray was used to screen for over 1,600 IgG autoantibodies against native, unmodified human proteins from each serum sample. Autoantibody profiles were compared between each RA subgroup and controls to identify differentially abundant autoantibodies (P< 0.05, Mann–WhitneyUtest; |Cliff’s delta (d)| > 0.33). Additionally, the relationship between RA patients’ autoantibody abundances and Clinical Disease Activity Index (CDAI) was examined for correlations between serum autoantibodies and disease activity (|Spearman’sρ| > 0.4 andP< 0.01).ResultsWe identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA– RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies higher in ACPA+ RA patients and ACPA– RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons. On the other hand, we found 30 and 25 autoantibodies lower in ACPA+ RA and ACPA– RA, respectively, of which eight autoantibodies were common in both comparisons. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with CDAI, but associate differently depending on the presence or absence of ACPA.ConclusionsACPA status in patients with RA determines not only the composition of the serum autoantibody repertoire, but also the correlative relationships between autoantibodies and disease activity. Notably, many of the autoantibodies identified herein were reported for the first time. Our findings warrant further investigation into the immunological differences between these two RA subgroups, and shed new light on the possible need for different treatment approaches.

Objective To identify longitudinal predictors of discordance between patients with rheumatoid arthritis (RA) and their health care providers, where patient global assessment of disease activity is substantially higher than provider global assessment. Methods This retrospective case-control study included 102 cases with positive discordance (i.e., ≥25 mm between patient and provider global assessments) and 102 controls without discordance who were matched for age, sex, RA duration, and Clinical Disease Activity Index (CDAI) score. Data were collected at the baseline visit (date of diagnosis or earliest available visit), the index visit (participation in a previous cross-sectional study), and at up to 11 additional visits before the index visit. Data included patient characteristics, disease activity measures, Disease Activity Score in 28 joints (3-variable) using the C-reactive protein level (DAS28-CRP), and medications. Data were analyzed by using linear and logistic regression models with smoothing splines for nonlinear trends. Results Overall, the mean age was 63 years, 75% of patients were female, and the mean RA duration was 10 years. Compared with controls, cases had higher rates of discordant visits during the 4 years before the index visit, and they had a higher CDAI score and DAS28-CRP earlier in the disease course. Cases more frequently had antinuclear antibodies, nonerosive disease, prior depression, or prior use of antidepressants or fibromyalgia medications. Disease-modifying medication use was not different between cases and controls. Conclusion The findings inform new hypotheses about the relationships of disease activity and antinuclear antibodies to the later occurrence of positive discordance among patients with RA.

Objective Due to an aging population, increasing prevalence of rheumatic disease, and a growing supply and demand gap of rheumatology providers, innovative solutions are needed to meet the needs of persons with rheumatic conditions. Nurse practitioners (NPs) and physician assistants (PAs) have been identified as a group of health professionals who could help address the workforce shortage. The Executive Committee of the Association of Rheumatology Health Professionals (ARHP), a division of the American College of Rheumatology (ACR), charged a task force to facilitate the preparation of NPs/PAs to work in a rheumatology practice setting. Methods The task force, consisting of private practice and academic rheumatologists, and NPs and PAs, from both adult and pediatric settings, conducted a needs assessment survey of current NPs and PAs to identify mechanisms for acquiring rheumatology knowledge. Through face-to-face and webinar meetings, and incorporating stakeholder feedback, the task force designed a rheumatology curriculum outline to enrich the training of new NPs and PAs joining rheumatology practice. Results Informed by the needs assessment data and stakeholders, an NP/PA rheumatology curriculum outline was developed and endorsed by the ACR Board of Directors for use by community-based and academic rheumatology practices, whether pediatric or adult, who desire to add NPs and PAs to their practice setting. Conclusion As rheumatology is facing workforce shortages, the ACR/ARHP rheumatology curriculum outline can be utilized to train NPs and PAs and create more efficient integration of NPs and PAs into rheumatology practice.

Background Flares in rheumatoid arthritis (RA) are common [1]. The shortage of readily available specialized care may hinder early detection and timely management of RA flares. Engaging non-physician rheumatology providers in care of RA flares may be beneficial. Objectives To evaluate the effect of a nurse-led flare management intervention versus usual care between rheumatology visits on flare occurrence and RA disease activity in patients with RA. Methods Patients with established RA (2010 ACR criteria) were randomized to the intervention versus usual care. The Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire was administered monthly during the 24-month follow-up to all patients in the intervention arm to assess flare status. The results of the FLARE-RA questionnaire and patient’s response to the question “Are you currently in a flare of your RA?” were recorded. Telephone nurse-led counseling or a visit with a mid-level rheumatology provider within 7 days of detection of flare was offered to patients in the intervention arm who indicated they were in flare. Patients in the usual care arm were followed by their rheumatology providers according to standards of care. OMERACT9 definition of flare was used to compare flare occurrence between the study arms. All patients completed satisfaction surveys at baseline and at the end of the follow-up. Results 150 patients with RA were randomized to intervention (n=75) versus usual care (n=75). At baseline, the majority of patients in the intervention arm (51%) and in the usual care (60%, p=0.32) were interested in expedited appointments with a rheumatology provider if in RA flare. There were no differences between the study arms at baseline in age, sex, tender joint counts, pain intensity, patient and physician global assessments, C-reactive protein levels, DAS28-CRP, CDAI, or SDAI. Despite randomization, patients in the intervention arm had lower swollen joint counts (1.1±2.7 vs 2.4, p=0.003) and Health Assessment Questionnaire (HAQ) score (0.6±0.6 vs 0.9±0.6, p=0.005) than those in the usual care arm. The number of patients in the intervention arm who completed the FLARE-RA questionnaires at baseline, 6, 12, 18, and 24 months was 75, 37, 27, 13, and 23, respectively. Patients in the intervention arm completed a median of 8.5 (range 1-24) questionnaires. RA flare was reported on 122 (19%) of these questionnaires; average FLARE-RA score: 2.57. Patients agreed to have an expedited clinic visit with a rheumatology provider during 39 (32%) of flares. The majority of patients preferred to self-manage their flare (76, 62%) or receive nursing advice over the phone 7 (6%). There were no differences in DAS28-CRP, CDAI, SDAI, anti-rheumatic treatment change by rheumatology provider, RA flare by OMERACT9 definition, or remission by CDAI between the study arms over 24-month follow-up. At the end of the study, a higher proportion of patients in the intervention arm (44%) versus the usual care arm (21%, p=0.04) reported positive effect of participation in the study on the management of RA flares. Conclusion The majority of patients expressed interest in expedited rheumatology appointments for their RA flares on their baseline patient-satisfaction survey. However, during the study, patients in the intervention arm largely preferred self-management and/or over-the-phone counseling. The nurse-led flare management intervention had no major effect on RA disease activity metrics over the 24-month follow-up. However, patients in the intervention arm reported a positive effect of the intervention. More studies are needed to further understand patient preferences for optimal RA flare management and to design interventions to meaningfully address these preferences. Reference [1] Bechman, K., et al. J Rheumatol, 2018. 45(11): p. 1515-21. Disclosure of Interests Elena Myasoedova Grant/research support from: Pfizer, Cynthia S. Crowson: None declared, Rachel Giblon: None declared, Daniel Schaffer: None declared, Kerry Wright: None declared, Eric Matteson Grant/research support from: Eric Matteson has received research grants from Pfizer and Sun Pharmaceutical Industries, Ltd. for work on the pathobiology of rheumatoid arthritis., Consultant for: Eric Matteson has received consultancy fees from Boehringer Ingelheim for an advisory board., John Davis Grant/research support from: Pfizer

To evaluate the effect of a flare management intervention guided by non-physician providers versus usual care between rheumatology visits on flare occurrence and rheumatoid arthritis (RA) disease activity.Adult patients with established RA (per 2010 ACR criteria, n = 150) were randomized to the intervention arm (n = 75) versus usual care (n = 75). The Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire was administered monthly during 24 months to all patients in the intervention arm to assess flare status. Telephone nurse-led counseling or an expedited visit with a rheumatology provider was offered to patients in the intervention arm who indicated they were in flare.Patients in the intervention arm completed a median of 8.5 (range 1-24) questionnaires. RA flare was reported on 122 (19%) of these questionnaires; average FLARE-RA score, 4.72 on 0 (no flare) to 10 (maximum flare) scale. Patients preferred an expedited clinic visit with a rheumatology provider during 39 (32%) of flares. The majority of patients preferred to self-manage their flare (76, 62%); some patients received nursing advice on flare management over the phone (7, 6%). There were no differences in RA flare by OMERACT9 definition, DAS28-CRP, CDAI, SDAI, anti-rheumatic treatment change by rheumatology provider, or remission by CDAI between the study arms over 24-month follow-up.The flare management intervention did not have any major effect on flare occurrence or RA disease activity metrics over the 24-month follow-up. The majority of patients in the intervention arm preferred self-management to an expedited visit with their rheumatology provider.ClinicalTrials.gov Identifier: NCT02382783 ( https://clinicaltrials.gov/ct2/show/NCT02382783 ) Key Points • The flare management intervention had no effect on rheumatoid arthritis (RA) disease activity. • Patients preferred self-management of their RA flares to expedited rheumatology provider visits.

Background Discordance between patients with rheumatoid arthritis (RA) and their rheumatology health care providers is a common and important problem. The objective of this study was to perform a comprehensive clinical evaluation of patient-provider discordance in RA. Methods A cross-sectional observational study was conducted of consecutive RA patients in a regional practice with an absolute difference of ≥ 25 points between patient and provider global assessments (possible points, 0–100). Data were collected for disease activity measures, clinical characteristics, comorbidities, and medications. In a prospective substudy, participants completed patient-reported outcome measures and underwent ultrasonographic assessment of synovial inflammation. Differences between the discordant and concordant groups were tested using χ2 and rank sum tests. Multivariable logistic regression was used to develop a clinical model of discordance. Results Patient-provider discordance affected 114 (32.5%) of 350 consecutive patients. Of the total population, 103 patients (29.5%) rated disease activity higher than their providers (i.e., ‘positive’ discordance); only 11 (3.1%) rated disease activity lower than their providers and were excluded from further analysis. Positive discordance correlated with negative rheumatoid factor and anticyclic citrullinated peptide antibodies, lack of joint erosions, presence of comorbid fibromyalgia or depression, and use of opioids, antidepressants, or anxiolytics, or fibromyalgia medications. In the prospective study, the group with positive discordance was distinguished by higher pain intensity, neuropathic type pain, chronic widespread pain and associated polysymptomatic distress, and limited functional health status. Depression was found to be an important mediator of positive discordance in low disease activity whereas the widespread pain index was an important mediator of positive discordance in moderate-to-high disease activity states. Ultrasonography scores did not reveal significant differences in synovial inflammation between discordant and concordant groups. Conclusions The findings provide a deeper understanding of patient-provider discordance than previously known. New insights from this study include the evidence that positive discordance is not associated with unrecognized joint inflammation by ultrasonography and that depression and fibromyalgia appear to play distinct roles in determining positive discordance. Further work is necessary to develop a comprehensive framework for patient-centered evaluation and management of RA and associated comorbidities in patients in the scenario of patient-provider discordance.