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Introduction: The efficacy of sarilumab and upadacitinib, in combination with disease-modifying antirheumatic drugs (DMARDs), was demonstrated in phase 3 clinical trials of patients with rheumatoid arthritis (RA) refractive to previous biologic DMARDs. In the absence of head-to-head clinical trials, the matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) estimate the relative efficacy of sarilumab and upadacitinib in patients with RA who had an inadequate response to previous biologic DMARDs. Methods:Patient-level data for sarilumab were obtained from the TARGET trial (NCT01709578) and published aggregate data for upadacitinib were obtained from the SELECT-BEYOND trial (NCT02706847). For the MAIC, individual patient data from the TARGET trial were assigned weights such that weighted mean baseline characteristics of the treatment effect modifiers matched those from SELECT-BEYOND. For the STC, the TARGET patient-level data and mean baseline values from SELECT-BEYOND were used to simulate sarilumab treatment effects for a SELECT-BEYOND population. Endpoints evaluated included the American College of Rheumatology (ACR) response criteria ACR20/50/70, Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS28-CRP) < 3.2, DAS28-CRP < 2.6, Simple Disease Activity Index (SDAI) < 3.3, and Clinical Disease Activity Index (CDAI) < 2.8 at 12 weeks. Results: The analysis included 365 patients from TARGET and aggregated data of 333 patients from SELECT-BEYOND. Matching for potential treatment effect baseline modifiers (i.e., age, oral glucocorticoid use, tender joint count of 68 counts, swollen joint count of 66 counts, serum CRP level, and patient global assessment of disease activity) resulted in a reduction of the effective sample size of TARGET population to 166. Following MAIC and STC analysis, the odds of achieving all aforementioned clinical outcomes versus placebo at week 12 were similar for sarilumab and upadacitinib. Conclusion: In the MAIC and STC analyses from TARGET and SELECT-BEYOND trials, the efficacy of sarilumab and upadacitinib were comparable.

The effect of treatment withdrawal on patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) whose disease is in sustained remission has not been well described. This analysis aimed to compare PRO changes in patients with RA following medication withdrawal and disease worsening.SEAM-RA (Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis) was a phase 3, multicenter, randomized withdrawal, double-blind controlled study in patients with RA taking methotrexate plus etanercept and in remission (Simple Disease Activity Index ≤3.3). Patient's Global Assessment of Disease Activity, Patient's Assessment of Joint Pain, Health Assessment Questionnaire-Disability Index, and 36-Item Short-Form Health Survey were evaluated for 48 weeks following methotrexate or etanercept withdrawal. Treatment differences for patients with versus without disease worsening were evaluated using a 2-sample t test for continuous end points and log-rank test for time-to-event end points.Of 253 patients, 121 experienced disease worsening and 132 did not. All PRO scores were similar to those of a general population at baseline and deteriorated over time across the study population. The PtGA and Patient's Assessment of Joint Pain values deteriorated less in those on etanercept monotherapy compared with methotrexate monotherapy. More patients with versus without disease worsening experienced deterioration that was greater than the minimal clinically important difference (MCID) for all PROs tested. In patients with disease worsening, PtGA deterioration more than the MCID preceded Simple Disease Activity Index disease worsening.Etanercept monotherapy showed benefit over methotrexate in maintaining PRO scores. Patients with disease worsening experienced a more rapid worsening of PtGA beyond the MCID versus patients without disease worsening.Categories: autoinflammatory disease, biological therapy, DMARDs, rheumatoid arthritis.

Patient-reported outcome (PRO) data have assumed increasing importance in the care of patients with rheumatoid arthritis (RA), yet physician-derived disease activity measures, such as Clinical Disease Activity Index (CDAI), remain the most accepted metrics to assess disease activity. The possibility that newer longitudinal PRO data might be used as a proxy for the CDAI has not been evaluated.Using data from a large pragmatic trial, we evaluated patients with RA initiating golimumab intravenous or infliximab. The classification target was low disease activity (LDA) (CDAI ≤10) at the first visit between months 3 and 12. Data were randomly partitioned into training (80%) and test (20%) data sets. Multiple machine learning (ML) methods (eg, random forests, gradient boosting, support vector machines) were used to classify CDAI disease activity category, conduct feature selection, and assess feature importance. Model performance evaluated cross-validated error, comparing different ML approaches using both training and test data.A total of 494 patients were analyzed, and 36.4% achieved LDA. The most important classification features included several Patient-Reported Outcomes Measurement Information System measures (social participation, pain interference, pain intensity, and physical function), patient global, and baseline CDAI. Among all ML methods, random forests performed best. Overall model accuracy and positive predictive values for all ML methods were approximately 80%.ML methods coupled with longitudinal PRO data appear useful and can achieve reasonable accuracy in classifying LDA among patients starting a new biologic. This approach has promise for real-world evidence generation in the common circumstance when physician-derived disease activity data are not available yet PRO measures are.

To determine whether multimorbidity is associated with treatment changes and achieving target disease activity thresholds in patients with active rheumatoid arthritis (RA).We conducted a retrospective cohort study of adults with active RA within the Rheumatology Informatics System for Effectiveness (RISE) registry. Multimorbidity was measured using RxRisk, a medication-based index of chronic disease. We used multivariable logistic regression models to assess the associations of multimorbidity with the odds of initiating a new disease-modifying antirheumatic drug (DMARD) in active RA, and among those initiating a new DMARD, the odds of achieving low disease activity or remission.We identified 15,626 patients using the Routine Assessment of Patient Index Data 3 (RAPID3) cohort and 5,733 patients using the Clinical Disease Activity Index (CDAI) cohort. All patients had active RA, of which 1,558 (RAPID3) and 834 (CDAI) initiated a new DMARD and had follow-up disease activity measures. Patients were middle aged, female, and predominantly White, and on average received medications from 6 to 7 RxRisk categories. Multimorbidity was not associated with new DMARD initiation in active RA. However, a greater burden of multimorbidity was associated with lower odds of achieving treatment targets (per 1-unit RxRisk: RAPID3 cohort odds ratio [OR] 0.95 [95% confidence interval (95% CI) 0.91, 0.98]; CDAI cohort OR 0.94 [95% CI 0.90, 0.99]). Those with the highest burden of multimorbidity had the lowest odds of achieving target RA disease activity (RAPID3 cohort OR 0.54 [95% CI 0.34, 0.85]; CDAI cohort OR 0.65 [95% CI 0.37, 1.15]).These findings from a large, real-world registry illustrate the potential impact of multimorbidity on treatment response and indicate that a more holistic management approach targeting multimorbidity may be needed to optimize RA disease control in these patients.

In patients with rheumatoid arthritis (RA), attaining remission or low disease activity (LDA), as recommended by the treat-to-target approach, has shown to yield improvement in symptoms and quality of life. However, limited evidence from real-world settings is available to support the premise that better disease control is associated with lower healthcare costs. This study fills in evidence gaps regarding the cost of care by RA disease activity (DA) states and by therapy.This retrospective cohort study linked medical and prescription claims from Optum Clinformatics Data Mart to electronic health record data from Illumination Health over 1/1/2010-3/31/2020. Mean annual costs for payers and patients were examined, stratifying on DA state and baseline use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics, and targeted synthetic (ts)DMARDs. Subgroup analysis examining within-person change in costs pre- and post-initiation of new therapy was also performed. Descriptive statistics, means, and boot-strapped confidence intervals were analyzed by DA state and by RA therapy. Furthermore, multivariate negative binomial regression analysis adjusting for key baseline characteristics was conducted.Of 2339 eligible patients, 19% were in remission, 40% in LDA, 29% in moderate DA (MDA), and 12% in high DA (HDA) at baseline. Mean annual costs during follow-up were substantially less for patients in remission ($40,072) versus those in MDA ($56,536) and HDA ($59,217). For patients in remission, csDMARD use was associated with the lowest mean annual cost ($25,575), tsDMARD was highest ($75,512), and tumor necrosis factor inhibitor (TNFi) ($69,846) and non-TNFi ($57,507) were intermediate. Among new TNFi (n = 137) and non-TNFi initiators (n = 107), 31% and 26% attained LDA/remission, respectively, and the time to achieve remission/LDA was numerically shorter in TNFi vs. non-TNFi initiators. For those on biologics, mean annual within-person medical and inpatient costs were lower after achieving LDA/remission, although pharmacy costs were higher.Cost of care increased with increasing DA state, with patients in remission having the lowest costs. Optimizing DA has the potential for substantial savings in healthcare costs, although may be partially offset by the high cost of targeted RA therapies.

Despite proven benefits, less than half of patients with rheumatoid arthritis (RA) are treated using a treat-to-target (TTT) strategy. Our objective was to identify critical discrepancies between rheumatologist and patient mental models related to the treatment of RA to inform interventions designed to increase implementation of TTT.We developed rheumatologist and patient mental models using the Mental Models Approach to Risk Communication. We conducted semistructured interviews to elicit views related to RA treatment decisions with 14 rheumatologists and 30 patients with RA. We also included responses (n = 284) to an open-ended question on a survey fielded to augment qualitative descriptions from the interviews. Interviews were transcribed and coded independently by two members of the research team.Rheumatologist and patient mental models for RA treatment are significantly more complex than the TTT model. Both consider domains (system factors and patient readiness) outside of disease activity measurement, target setting, and risk versus benefit assessment in their decision-making. Furthermore, specific factors were found to be unique to each model. For example, the physician model stresses the importance of evaluating disease activity over time and patient adherence. In contrast, patients discussed the impact of chronic disease weariness, medication-related fatigue, the importance of feeling adequately informed, and stress associated with changing medications.We found several discrepancies primarily related to information gaps and differences in how patients and physicians value trade-offs that can serve as specific targets to improve patient-physician communication and ultimately inform interventions to improve uptake of TTT.

Objective: The study objective was to prioritize topics for future patient-centered research to increase uptake of common vaccines, such as for pneumococcal pneumonia, influenza, herpes zoster, human papillomavirus, and severe acute respiratory syndrome coronavirus 2, among adults living with autoimmune conditions. Methods: A steering committee (SC) was formed that included clinicians, patients, patient advocates, and researchers associated with rheumatic diseases (psoriatic arthritis, rheumatoid arthritis, vasculitis), inflammatory bowel disease, and multiple sclerosis. Through a scoping review and discussions, SC members identified research topics regarding vaccine uptake and/or hesitancy for prioritization. A larger multistakeholder alliance that included patients and patient advocates, clinicians, researchers, policy makers, regulators, and vaccine manufacturers conducted a modified Delphi exercise online with three rating rounds and one ranking round. Frequency analysis and comparisons across stakeholder groups were conducted. A weighted ranking score was generated for each item in the ranking round for final prioritization. Results: Through the Delphi process, 33 research topics were identified, of which 13 topics were rated as critical by more than 70% of all stakeholders (n = 31). The two highest ranked critical topics per the full stakeholder group were “How well a vaccine works for adults with autoimmune conditions” and “How beliefs about vaccine safety affect vaccine uptake.”. Conclusion: A multistakeholder group identified key topics as critically important priorities for future research to decrease vaccine hesitancy and improve uptake of vaccines for adults with autoimmune conditions.

Background Biologic therapies are often prescribed for patients with rheumatoid arthritis (RA) who have inadequate responses to or are intolerant of methotrexate (MTX) and patients with poor prognostic indicators. This post hoc analysis evaluated effectiveness and safety of intravenous golimumab + MTX vs golimumab without MTX in RA patients. Methods AWARE, a real-world, prospective and pragmatic, Phase 4 study, compared effectiveness and safety of golimumab and infliximab in biologic-naïve and biologic-experienced patients. All treatment decisions were at the discretion of the treating rheumatologist. Effectiveness was evaluated by mean change in CDAI scores at Months 6 and 12. Safety was monitored through approximately 1 year. Results Among 685 golimumab-treated patients, 420 (61%) received concomitant MTX during the study and 265 (39%) did not receive MTX after enrollment; 63% and 72%, respectively, discontinued the study. Relative to golimumab without MTX, golimumab + MTX patients had shorter mean disease duration (8.7 vs 10.0 years) and a lower proportion received prior biologics (60% vs 72%); mean ± standard deviation (SD) baseline CDAI scores were similar (30.8 ± 15.1 and 32.6 ± 15.4). Mean ± SD changes from baseline in CDAI scores at Months 6 and 12, respectively, were similar with golimumab + MTX (− 10.2 ± 14.2 and − 10.8 ± 13.8) and golimumab without MTX (− 9.6 ± 12.9 and − 9.9 ± 13.1). The incidence of adverse events/100 patient-years (PY) (95% confidence interval [CI]) was 155.6 (145.6, 166.1) for golimumab + MTX and 191.2 (176.2, 207.1) for golimumab without MTX; infections were the most common type. The incidence of infusion reactions/100PY (95% CI) was 2.1 (1.1, 3.6) for golimumab + MTX versus 5.1 (2.9, 8.3) for golimumab without MTX; none were considered serious. For golimumab + MTX versus golimumab without MTX, rates/100PY (95% CI) of serious infections, opportunistic infections, and malignancies were 2.6 (1.5, 4.3) versus 7.0 (4.4, 10.6), 0.9 (0.3, 2.0) versus 2.6 (1.1, 5.0), and 3.0 (1.7, 4.7) versus 1.0 (0.2, 2.8), respectively. Conclusions Mean change in CDAI score in the golimumab without MTX group was generally similar to that of the golimumab + MTX group through 1 year, regardless of prior biologic therapy. Adverse events were consistent with the known IV golimumab safety profile. These results provide real world evidential data that may assist healthcare providers and patients with RA in making informed treatment decisions. Trial registration: clinicaltrials.gov NCT02728934 05/04/2016.

The association between disease activity and infection risk among patients with rheumatoid arthritis (RA) is not clear, and it is challenging to determine because of confounding due to the effects of RA treatments and comorbidities.Using RA patients in the CorEvitas registry with Medicare coverage in 2006-2019, we identified eligible patients who had at least one visit with moderate disease activity based on the clinical disease activity index (CDAI10 and=22). Follow-up started at the subsequent CorEvitas visit. Hospitalized infection during follow-up was assessed in linked Medicare data. We calculated the incidence rate of hospitalized infection for patients in remission, low, and moderate disease activity and estimated the effect of time-varying CDAI on hospitalized infection by controlling for baseline and time-dependent confounders using marginal structural models (MSM).A total of 3,254 RA patients were eligible for analysis, among which 529 hospitalized infections were identified during follow-up. The crude incidence of hospitalized infection was 3.8 per 100 person years for patients in remission, 6.6 for low disease activity and 8.0 for moderate disease activity. Using MSMs, and compared to being in remission, the hazard ratio of hospitalized infection associated with low disease activity was 1.60 (95% CI: 1.13-2.28) and for moderate disease activity was 1.83 (95% CI: 1.30-2.64).The risk of hospitalized infection was higher for RA patients in low or moderate disease activity compared to those in remission after accounting for the interplay of disease activity, RA treatments, treatment switching, and other potential confounders.

To assess the perceptions and preferences of telemedicine among patients with autoimmune rheumatic diseases during the COVID-19 pandemic.We conducted an online survey among patients with autoimmune rheumatic diseases. Attitudes about telemedicine (i.e., telemedicine acceptability), evaluated using the validated Telemedicine Perception Questionnaire (TMPQ), and visit satisfaction were assessed for different telemedicine experiences and types of autoimmune rheumatic disease.Of 3,369 invitations, 819 responses were received. Participants had a mean ± SD age of 58.6 ± 11.6 years and were mostly White (n = 759, or 92.7%) and female (n = 702, or 85.7%). Of the 618 participants who said that telemedicine was available to them, 449 (72.7%) reported having a telemedicine visit, with 303 (67.5%) reporting attending a telemedicine video visit. On a 0 to 10 scale, the mean ± SD visit satisfaction score was 7.3 ± 1.8, with 25.8% of respondents being very satisfied (scores of 9 or 10). Video visits and higher TMPQ scores were associated with higher satisfaction. Compared to those who did not experience a telemedicine visit, patients who did were more likely to prefer telemedicine (video or phone) for routine visits (73.7% versus 44.3%; P 0.001), reviewing test results (64.8% versus 53.8%; P 0.001), when considering changing medications (40.5% versus 26.8%; P 0.001), and when starting a new injectable medication (18.9% versus 12.7%; P = 0.02).During the COVID-19 pandemic, patients with autoimmune rheumatic diseases frequently had telemedicine visits, with the majority held via video, and were satisfied with these visits. These results suggest that because patients prefer telemedicine for certain visit reasons, maximizing effective use of telemedicine will require personalized patient scheduling.

The aim of this study was to characterize employment, work productivity, and biologic disease-modifying anti-rheumatic drug (bDMARD) treatment in a predominantly female population of axial spondyloarthritis (axSpA) patients in a real-world setting.This was a cross-sectional study of axSpA participants within the ArthritisPower registry. Outcomes were assessed with surveys (Work Productivity and Activity Impairment [WPAI], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], and Patient-Reported Outcomes Measurement Information System instruments) and compared between subgroups (employed vs. not employed; taking vs. not taking a bDMARD).Among the 195 participants, 117 (60.0%) were employed and 78 (40.0%) were not employed entirely or partially due to axSpA. The mean age of the participants was 47.6 years and 86.7% were female. Current bDMARD use was reported by 57.4% of those surveyed (59.8% employed vs. 53.9% not employed; p = 0.408). Compared to not employed participants, employed participants had more favorable disease activity (BASDAI 6.0 vs. 7.6; p 0.001) and overall health (self-rated health 2.5 vs. 1.8; p 0.001). Employed participants, compared to not employed participants, were diagnosed at an earlier age (36.0 vs. 42.5 years, respectively) and experienced a shorter time between symptom onset and diagnosis (9.5 vs. 13.6 years, respectively). Employed participants reported missing on average 6.5 days of work and experienced a 52.7% impairment on work productivity due to axSpA over a 3-month period. Absenteeism and presenteeism were statistically similar between participants taking a bDMARD versus those not taking a bDMARD.Although bDMARD treatment rates were similar between employed and not employed participants, disease activity and overall health were better in employed than non-employed participants. Employed participants experienced substantial work productivity impairment due to axSpA.

The risk of herpes zoster (HZ) and HZ-related complications is increased in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) relative to the general population; therefore, HZ vaccination is recommended in these patient groups. In this literature-based review, we summarise the available evidence on the use of HZ vaccines in patients with RA and PsA, and discuss strategies for managing breakthrough infection. Currently available data show suboptimal rates of HZ vaccination among these patients and highlight a need for strategies to improve HZ vaccination programmes in clinical practice. Further clinical studies are also required to optimise the use of HZ vaccines in patients with RA and PsA, particularly with regard to determining the impact of different immunosuppressive therapy regimens on vaccine immunogenicity and, ultimately, efficacy, as well as the impact of vaccination on disease activity and safety.

Frailty is associated with disability and mortality independent of age. Although studies have evaluated frailty in rheumatoid arthritis (RA), information on the prevalence of frailty in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) is limited. We aimed to determine the prevalence of frailty in AS and PsA and to evaluate whether characteristics known to be associated with frailty, including anxiety, differ among these three types of inflammatory arthritis.We performed a cross sectional study of Centers for MedicareMedicaid Services (CMS) beneficiaries aged 65 years or older with AS, PsA, or RA enrolled in 2014. We operationalized frailty using a validated claims-based frailty index. We also explored the prevalence of frailty among CMS beneficiaries younger than age 65 years with work disability, a younger population that also may be at risk of frailty.The prevalence of frailty in beneficiaries aged 65 years or older with AS and PsA was 45.2% and 46.7%, respectively, significantly lower than in RA (65.9%, P 0.05). The prevalence of frailty in beneficiaries less than 65 years old was much lower overall, though still highest in RA; 11.7%, 4.4%, and 7.0% in RA, AS, and PsA, respectively (P 0.05). Anxiety was significantly associated with frailty in subjects of all ages, particularly among those less than 65 years old (P 0.05).Almost half of beneficiaries with AS or PsA aged 65 years old or older were frail, higher than in younger disabled beneficiaries. Further studies are needed to understand the risks of developing frailty in these diseases. Frailty was associated with anxiety, particularly in the younger age groups.

Objective B cells can become activated in germinal center (GC) reactions in secondary lymphoid tissue and ectopic GCs in synovium in RA that may be TNF and lymphotoxin (LT) dependent. Here we characterized the peripheral B cell compartment longitudinally during anti-TNF therapy in RA. Methods Participants were randomized in a 2:1 ratio to receive standard dosing regimens of etanercept (n=43) or adalimumab (n=20) for 24 weeks. Eligible participants met the 1987 ACR criteria for RA, clinically active (DAS28>4.4), and on stable doses of methotrexate. The primary mechanistic endpoint was the change in switched memory B cell fraction from baseline to week 12 in each treatment group. Results B cell subsets remained surprisingly stable over the course of the study regardless of treatment group, with no significant change in memory B cells. Blockade of TNF and LT with etanercept compared to TNF blockade alone with adalimumab did not translate into significant differences in clinical response. Multiple activated B cell populations including CD21- double negative memory and activated naive were higher in RA non-responders (NR) at all time points, and CD95+ activated B cells increased with anti-TNF in the NR group. In contrast, transitional B cells- a putative regulatory subset- were lower in the NRs. Conclusions Overall, our results support that peripheral blood B cell subsets are remarkably stable in RA and not differentially impacted by dual blockade of TNF and LT with etanercept or single blockade of TNF with adalimumab. Activated B cells do associate with a less robust response.

This study's objective was to test whether an online video intervention discussing appropriate treatment escalation improves willingness to change treatment in people living with rheumatoid arthritis (RA).We conducted a controlled, randomized trial among patients with RA enrolled in ArthritisPower, a United States patient registry. We recruited participants by email and surveyed their assessment of disease activity (patient global), satisfaction with disease control (patient acceptable symptom state), attitudes about RA medications, decisional conflict (decisional conflict scale), and willingness to modify RA treatment (choice predisposition scale, higher scores are better) if or when recommended by their rheumatologist. Intervention groups watched educational videos relevant to a treat-to-target (T2T) strategy, whereas control groups viewed vaccination-related videos as an "attention control." We compared the between-group difference in patients' willingness to modify RA treatment (primary outcome) and difference in decisional conflict about changing RA treatment (secondary outcome) after watching the videos using t tests.Participants with self-reported RA (n = 208) were 90% White and 90% women, with a mean (standard deviation) age of 50 (11) years, and 52% reported familiarity with the RA T2T strategy. We found a significant improvement in between-group difference in willingness to change RA treatment among intervention versus control participants (0.49 [95% confidence interval 0.09-0.88], P = 0.02). The effect size (Glass's delta) for the intervention was 0.48. Decisional conflict about treatment change decreased, but the between-group difference was not significant.This novel educational patient-directed intervention discussing appropriate treatment escalation was associated with improved willingness to change RA treatment if or when recommended by a rheumatologist. Further studies should evaluate whether this change in patients' predisposition translates into actual treatment escalation.

To evaluate the effectiveness of 2 interventions, including the DrugFactsBox format for presenting written medication information and the SMART (Strategic Memory Advanced Reasoning Training) program designed to enhance gist (i.e., "bottom-line" meaning) reasoning ability.We used a 2 × 2 factorial research design. A total of 286 patients with rheumatoid arthritis were randomly assigned to 1 of 4 groups, including DrugFactsBox with the SMART program, DrugFactsBox without the SMART program, other consumer medication information (CMI) with the SMART program, and other CMI without the SMART program. Data were collected via telephone interviews and online questionnaires at 4 time points, including baseline and 6-week, 3-month, and 6-month time points following baseline. The primary outcome variable was informed decision-making, which was defined as making a value-consistent decision concerning use of disease-modifying antirheumatic drugs based on adequate knowledge.We found no main effects for the 2 interventions, either alone or in combination. However, there was a significant interaction between assignment to the SMART/no SMART groups and informed decision-making at baseline. Among participants in the SMART groups who did not meet the criteria for informed decision-making at baseline, 42.5% met the criteria at the 6-month follow-up, compared to 23.6% of participants in the no SMART groups (mean difference 18.9 [95% confidence interval 5.6, 32.2]; P = 0.007). This difference was driven by increased knowledge in the SMART groups. Among participants who met the criteria for informed decision-making at baseline, the difference between the SMART and no SMART groups was not statistically significant.Participation in a theory-driven program to enhance gist reasoning may have a beneficial effect on informed decision-making among patients with inadequate knowledge concerning therapeutic options.

Risk of herpes zoster (HZ) is increased with Janus kinase inhibitor use. We evaluated clinical study data relating to HZ management in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) receiving tofacitinib.This post hoc analysis included data from 21 RA and 3 PsA clinical studies; data were pooled for tofacitinib doses. Outcomes of HZ events (serious and non-serious) and tofacitinib treatment changes were evaluated in response to first and second HZ events. Median time to resolution was stratified by dermatomal involvement, history of HZ prior to tofacitinib, changes to tofacitinib treatment, anti-viral and corticosteroid use, and tofacitinib dose.Seven hundred eighty-three (11.1%, N = 7061) patients with RA experienced ≥ 1 HZ event, 63 (8.0%) of whom had ≥ 2 HZ events. In patients with PsA, 36 (4.6%, N = 783) experienced ≥ 1 HZ event, 1 (2.8%) of whom had ≥ 2 HZ events. For most HZ events, tofacitinib treatment was unchanged or temporarily discontinued. The majority of patients received anti-viral treatment, most within 3 days of onset. Post-herpetic neuralgia developed in 6.9% and 3.2% of patients with RA with first and second events, respectively, and in 2.8% of patients with PsA with a first event. Most first and second events resolved (RA: 97.6% and 96.8%, respectively; PsA: 94.4% and 100%, respectively). Median time to resolution was 22.0 days for first and 15.0 days for second events for RA and 20.5 days for first and 11.0 days for second events (n = 1) for PsA. Time to resolution of first events for RA and PsA was generally numerically shorter for patients with single dermatomal HZ, history of HZ, or anti-viral use versus those without.Among patients receiving tofacitinib, recurrent events were more common in patients with RA versus PsA; HZ duration was shorter for repeat events.NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02187055, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364.Patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) have weakened immune responses and are more likely to get herpes zoster (HZ; also known as shingles) infections compared with the general population. Patients who receive treatments for RA or PsA that have an effect on their immune system are more likely to get HZ. Here, we assessed how common HZ was in patients with RA or PsA who were given tofacitinib during clinical trials, the management of these infections, and how this affected the course of the infection. Approximately 1 in 10 patients with RA and 1 in 20 patients with PsA had HZ. Of those patients who had HZ, 1 in 12 with RA and 1 in 36 with PsA were infected again at a later point. A small number of patients also had long-lasting pain after HZ infection. When patients had a HZ infection, most either continued treatment with tofacitinib or paused treatment for a period of time. Pausing or continuing treatment did not appear to affect how long the infection lasted or whether patients had another infection. Most patients received treatment for HZ infection, and patients who were treated had shorter infections. In most patients, infections cleared up and were more likely to clear up more quickly when patients had HZ previously.

Introduction The magnitude and frequency of temporally related methotrexate (MTX)-associated side effects in rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients are difficult to quantify using traditional research methods. As proof of concept designed in part to implement digital data collection for remote patient monitoring, we conducted a study implementing self-controlled case series analytic methods to understand MTX-related symptoms in RA or PsA. Methods In study phase 1, adults with RA or PsA from the ArthritisPower® Registry (past or current oral MTX users) participated in a cross-sectional survey. In phase 2, current MTX users participated in a longitudinal study and completed the Patient-Reported Outcomes Measurement Information System (PROMIS®) 1-day nausea/vomiting and fatigue measure. Within-person change in PROMIS scores between risk (6–36 h post-dose) and control (96–144 h post-dose) windows were compared using mixed models. Results The baseline survey was completed by 671 participants (mean age: 54 years, 88% female, 92% white, 79% with RA). Among current MTX users (353/671 [53%]), most reported MTX-associated side effects (216/353 [61%]), most frequently fatigue (161/353 [46%]). Among phase 2 participants with (n = 39) and without (n = 84) baseline nausea, mean increase in PROMIS nausea was 5.1 units (P

Objective Aims were to 1) to characterize patient decision-making with treatment for axial spondyloarthritis (axSpA) and 2) to explore relationships among decision-making, treatment satisfaction, and biologic disease modifying antirheumatic drugs (bDMARDs). Methods ArthritisPower participants with physician-diagnosed axSpA were invited to complete an online survey about their treatment and their most recent physician visit. Analysis compared treatment decision by satisfaction and bDMARD status. Results Among the 274 participants, 87.2% were female, and the mean age was 50 years. Of participants, 79.5% had researched treatment before their most recent physician visit, and 56.9% discussed treatment change at their most recent physician visit. Of treatment-change discussions, 69.2% of them were related to escalation, compared with deescalation (27.6%) and/or switching (39.1%). Among those participants who discussed a change, 73.7% agreed to it because they felt that their disease was not being controlled (54.9%) or felt that it could be better controlled on new treatment (20.3%). Top symptoms prompting change were back/buttock pain (63.3%), other joint pain (55.1%), and fatigue (54.1%). Among bDMARD-treated participants (n = 128), important factors for treatment decisions were prevention of long-term axSpA consequences (92.9%) and doctor's advice (87.5%). Among 43.4% of participants reporting treatment dissatisfaction, 37% did not discuss treatment change. Current bDMARD use was more common in satisfied (61.9%) than dissatisfied participants (26.9%). Conclusion In this cross-sectional study of a predominantly female axSpA population, patients frequently researched treatment options and discussed escalation with their providers. Under two-thirds of participants who were dissatisfied with treatment discussed changes at their most recent visit. Current bDMARD use was associated with higher satisfaction, and bDMARD users considered prevention of long-term consequences and doctor's advice to be very important for decision-making.

OBJECTIVE Glucocorticoids are recommended for short-term use in rheumatoid arthritis (RA), but many patients continue receiving long-term therapy. We evaluated the variability in glucocorticoid prescribing across rheumatologists to inform interventions to limit long-term glucocorticoid use to the lowest dose necessary. METHODS Two cohorts were created using Medicare data from 2006 to 2015. Using cohort 1 (RA patients receiving disease-modifying antirheumatic drugs [DMARDs]), we calculated each rheumatologist's "provider preference" for glucocorticoids (frequency of use compared to other providers), using the ratio of observed to expected number of patients receiving glucocorticoids to account for case mix. In cohort 2 (RA patients receiving stable DMARD therapy), we evaluated whether provider preference for glucocorticoids could independently predict use of ≥5 mg/day of glucocorticoids 6-9 months after initiation of DMARD therapy. RESULTS Using cohort 1 (1,272,644 yearly observations; 385,597 patients), we calculated provider preference among 6,875 rheumatologists (28,936 yearly observations). Provider preference was highly variable, with physicians at the lowest and upper quartiles prescribing glucocorticoids 33% less often to 31% more often (25th and 75th percentiles, respectively) than expected. In cohort 2 (155,539 patients receiving stable DMARD therapy), provider preference was strongly associated with glucocorticoid use ≥5 mg/day at 6-9 months, with a predicted probability of use of 22% (95% confidence interval [95% CI] 21.7-22.7) versus 11% (95% CI 10.2-10.9) for a patient seeing a provider in the highest versus lowest quintile of preference. CONCLUSION Glucocorticoid prescribing for RA varies greatly among rheumatologists, and provider preference is one of the strongest predictors of a patient's long-term glucocorticoid use. These findings raise quality of care concerns and highlight the need for stronger evidence to guide RA treatment.

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

Introduction Although short-term clinical trials have demonstrated that switching from infliximab (INF) bio-originator to its biosimilar is safe with no significant loss of efficacy, there are limited real-world data comparing their patterns of use and adherence. Methods Using 2015–2018 IBM Marketscan data, we established 4 cohorts of patients with at least one administration or pharmacy claim for INF bio-originator or biosimilar in 2017, including INF naïve biosimilar users, INF prevalent biosimilar users, INF naïve bio-originator users, and INF prevalent bio-originator users, defined according to their prior use of INF from 2015 to their first INF administration in 2017. The proportion of days covered (PDC) was calculated for patients with at least 6, 12, or 18 months of follow-up time. Factors associated with optimal adherence (PDC > 80%) were evaluated using log-binomial models. Results We identified 96 INF naïve biosimilar users, 223 INF prevalent biosimilar users, 2,149 INF naïve bio-originator users, and 10,970 INF prevalent bio-originator users. At the end of 18 months of follow-up, 64% of INF prevalent bio-originators, 48% of INF naïve biosimilars, 41% of INF naïve bio-originators, and 36% of INF prevalent biosimilars had optimal adherence. Depression, previous hospitalization, and greater use of prior biologics were negatively associated with adherence, whereas IBD diagnoses (referent to RA) and age 55–64 (referent to Conclusion INF prevalent users had higher adherence in our analyses than INF naïve users. However, further studies with larger sample size are needed to evaluate INF biosimilar users’ adherence.

Objective Evaluate tolerability and effectiveness of golimumab-IV versus infliximab in patients with rheumatoid arthritis (RA) in a real-world setting. Methods AWARE, a prospective, real-world, pragmatic, observational, multicenter, phase 4 study, enrolled RA patients when initiating golimumab-IV or infliximab. Treatment decisions were made by the treating rheumatologist. The approved doses for RA are 2 mg/kg at weeks 0, 4, then Q8W for golimumab-IV and 3 mg/kg at weeks 0, 2, 6, then Q8W (dose escalation permitted) for infliximab. A prespecified formal interim analysis was conducted. The primary endpoint was the incidence of infusion reactions (any adverse event that occurred during or within 1 h of infusion) through week 52. Major secondary endpoints were mean change from baseline in CDAI at months 6 and 12 in biologic-naïve patients (non-inferiority margin in the CDAI = 6). Baseline characteristics were adjusted using propensity scores with inverse probability of treatment weights (IPTW). Results In the formal interim analysis (golimumab-IV, n = 479; infliximab, n = 354), the incidence of infusion reactions was significantly lower with golimumab-IV vs. infliximab (3.6 vs. 17.6%, p

The SARS-CoV-2 global pandemic resulted in major disruptions to medical care. We aimed to understand changes in outpatient care delivery and use of telemedicine in U.S. rheumatology practices during this period. Rheumatology Informatics System Effectiveness (RISE) is a national, EHR-enabled registry that passively collects data on all patients seen by participating practices. Included practices were required to have been participating in RISE from January 2019 through August 2020 (N = 213). We compared total visit counts and telemedicine visits during March-August 2020 to March-August 2019 and stratified by locations in states with shelter-in-place (SIP) orders. We assessed characteristics of patients within each practice, including primary rheumatic diagnosis and disease activity scores, where available. We included 213 practices with 945,160 patients. Overall, we found visit counts decreased by 10.9% (from 1,302,455 to 1,161,051) between March and August 2020 compared to 2019; this drop was most dramatic during the month of April (-22.3%). Telemedicine visits increased from 0% to a mean of 12.1%. Practices in SIP states had more dramatic decreases in visits, (11.5% vs. 5.3%). We found no major differences in primary diagnoses or disease activity across the two periods. We detected a meaningful decrease in rheumatology visits in March-August 2020 during the SARS-CoV-2 global pandemic compared to the year prior with a concomitant increase in the use of telemedicine. Future work should address possible adverse consequences to patient outcomes due to decreased contact with clinicians.

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

Introduction Timely matching of patients to beneficial targeted therapy is an unmet need in rheumatoid arthritis (RA). A molecular signature response classifier (MSRC) that predicts which patients with RA are unlikely to respond to tumor necrosis factor-α inhibitor (TNFi) therapy would have wide clinical utility. Methods The protein–protein interaction map specific to the rheumatoid arthritis pathophysiology and gene expression data in blood patient samples was used to discover a molecular signature of non-response to TNFi therapy. Inadequate response predictions were validated in blood samples from the CERTAIN cohort and a multicenter blinded prospective observational clinical study (NETWORK-004) among 391 targeted therapy-naïve and 113 TNFi-exposed patient samples. The primary endpoint evaluated the ability of the MSRC to identify patients who inadequately responded to TNFi therapy at 6 months according to ACR50. Additional endpoints evaluated the prediction of inadequate response at 3 and 6 months by ACR70, DAS28-CRP, and CDAI. Results The 23-feature molecular signature considers pathways upstream and downstream of TNFα involvement in RA pathophysiology. Predictive performance was consistent between the CERTAIN cohort and NETWORK-004 study. The NETWORK-004 study met primary and secondary endpoints. A molecular signature of non-response was detected in 45% of targeted therapy-naïve patients. The MSRC had an area under the curve (AUC) of 0.64 and patients were unlikely to adequately respond to TNFi therapy according to ACR50 at 6 months with an odds ratio of 4.1 (95% confidence interval 2.0–8.3, p value 0.0001). Odds ratios (3.4–8.8) were significant (p value, Plain Language Summary A blood-based molecular signature response classifier (MSRC) integrating next-generation RNA sequencing data with clinical features predicts the likelihood that a patient with rheumatoid arthritis will have an inadequate response to TNFi therapy. Treatment selection guided by test results, with likely inadequate responders appropriately redirected to a different therapy, could improve response rates to TNFi therapies, generate healthcare cost savings, and increase rheumatologists’ confidence in prescribing decisions and altered treatment choices. The MSRC described in this study predicts the likelihood of inadequate response to TNFi therapies among targeted therapy-naïve and TNFi-exposed patients in a multicenter, 24-week blinded prospective clinical study: NETWORK-004. Patients with a molecular signature of non-response are less likely to have an adequate response to TNFi therapies than those patients lacking the signature according to ACR50, ACR70, CDAI, and DAS28-CRP with significant odds ratios of 3.4–8.8 for targeted therapy-naïve patients and 3.3–26.6 for TNFi-exposed patients. This MSRC provides a solution to the long-standing need for precision medicine tools to predict drug response in rheumatoid arthritis—a heterogeneous and progressive disease with an abundance of therapeutic options. These data validate the performance of the MSRC in a blinded prospective clinical study of targeted therapy-naïve and TNFi therapy-exposed patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00330-y.

Objective.To determine the association of serum urate (SU) levels with sudden cardiac death and incident coronary heart disease (CHD), separately, among adults without a history of CHD.Methods.We conducted a case-cohort analysis of Black and White participants aged ≥ 45 years enrolled in the REason for Geographic And Racial Differences in Stroke (REGARDS) study without a history of CHD at baseline between 2003 and 2007. Participants were followed for sudden cardiac death or incident CHD (i.e., myocardial infarction [MI] or death from CHD excluding sudden cardiac death) through December 31, 2013. Baseline SU was measured in a random sample of participants (n = 840) and among participants who experienced sudden cardiac death (n = 235) or incident CHD (n = 851) during follow-up.Results.Participants with higher SU levels were older and more likely to be male or Black. The crude HR (95% CI) per 1 mg/dL higher SU level was 1.26 (1.14–1.40) for sudden cardiac death and 1.17 (1.09–1.26) for incident CHD. After adjustment for age, sex, race, and cardiovascular risk factors, the HR (95% CI) per 1 mg/dL higher SU level was 1.19 (1.03–1.37) for sudden cardiac death and 1.05 (0.96–1.15) for incident CHD. HRs for sudden cardiac death were numerically higher among participants aged 45–64 vs ≥ 65 years, without vs with diabetes, and among those of White vs Black race, although P values for effect modification were all ≥ 0.05.Conclusion.Higher SU levels were associated with an increased risk for sudden cardiac death but not with incident CHD.

Objective This study explored how women's beliefs about drug safety and interactions with their health care providers influenced their decisions to continue arthritis medications during pregnancy and lactation. Methods We collaborated with ArthritisPower, a patient-powered research network, and CreakyJoints, its partner online community, to develop and disseminate a survey among members with inflammatory arthritis who had at least one pregnancy after diagnosis. Participants' free-text responses were evaluated by using thematic analysis. Results Women in the sample were 40 years old on average (N = 66). Nineteen of their pregnancies had ended in fetal loss. Fifteen percent of all pregnancies were exposed to methotrexate. Among women who used safe arthritis medications, up to 80% discontinued treatment either in preparation for pregnancy or during pregnancy or lactation. Women's decisions to continue medications during pregnancy were influenced by their perceptions of safety and advisement from health care providers, although they often described that advice about medication safety was inconsistent between providers. Conclusion Women often chose to endure active inflammatory arthritis rather than to use disease-modifying antirheumatic drugs because of concerns about medication safety during pregnancy and lactation. Conflicting medical advice from health care providers undermined patients' trust in their providers and in the safety of their medications. The high rate of peripartum exposure to methotrexate, a fetotoxic drug, underscores the need for better family planning care for women with childbearing potential.

OBJECTIVE. To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS. This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS. This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION. Application of these recommendations should consider patients’ individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.

The efficacy and safety of coronavirus disease 2019 (COVID-19) vaccination in patients with autoimmune inflammatory diseases (AIRDs) who are treated with immunomodulatory therapies was the focus of a symposium at the 2021 virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). The keynote address was delivered by Dr. Jeffrey Curtis, chair of the American College of Rheumatology COVID-19 Vaccine Clinical Guidance task force, detailing what we do and do not know about vaccine efficacy and safety in patients with AIRDs and providing guidance about the need for modification of dosing in some immunomodulatory medications for optimal vaccine response. A consensus of the task force was that all patients with AIRDs should be vaccinated as soon as it is allowed in their respective locations, since the benefits of increased protection against COVID-19 infection outweigh the potential for vaccination reactions, including flares of underlying disease, or for reduced efficacy of vaccination because of disease state or medications. Key issues among patient research partners with psoriatic disease expressed in the premeeting survey and panel discussion/question-and-answer period included: vaccine efficacy and safety, the need to continue safe social habits and masking, how to assess efficacy of vaccination, how to deal with vaccine hesitancy among social contacts, medication management relative to vaccination, and concerns about the adequacy of ongoing telehealth visits vs the convenience of that technology.

BACKGROUND: We aimed to compare concerns, social distancing, health care disruptions, and telemedicine use in patients with autoimmune rheumatic disease (ARD) and non-ARD and to evaluate factors associated with immunomodulatory medication interruptions. METHODS: Patients in a multistate community rheumatology practice network completed surveys from April 2020 to May 2020. Adults with common ARD (rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus) or non-ARD (gout, osteoarthritis, osteoporosis) were evaluated. Concerns about coronavirus disease 2019 (COVID-19), social distancing, health care disruptions, and telemedicine use were compared in patients with ARD versus non-ARD, adjusting for demographics, rural residence, and zipcode-based measures of socioeconomic status and COVID-19 activity. Factors associated with medication interruptions were assessed in patients with ARD. RESULTS: Surveys were completed by 2319/36 193 (6.4%) patients with non-ARD and 6885/64 303 (10.7%) with ARD. Concerns about COVID-19 and social distancing behaviors were similar in both groups, although patients receiving a biologic or Janus kinase (JAK) inhibitor reported greater concerns and were more likely to avoid friends/family, stores, or leaving the house. Patients with ARD were less likely to avoid office visits (45.2% vs. 51.0%, odds ratio [OR] 0.79 [0.70-0.89]) with similar telemedicine use. Immunomodulatory medications were stopped in 9.7% of patients with ARD, usually (86.9%) without a physician recommendation. Compared with patients with an office visit, the likelihood of stopping medication was higher for patients with a telemedicine visit (OR 1.54 [1.19-1.99]) but highest for patients with no visits (OR 2.26 [1.79-2.86]). CONCLUSION: Patients with ARD and non-ARD reported similar concerns about COVID-19 and similar social distancing behaviors. Missed office visits were strongly associated with interruptions in immunomodulatory medication.

Objective To provide guidance to rheumatology providers on the use of coronavirus disease 2019 (COVID-19) vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). Methods A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9-point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings. Results Despite a paucity of direct evidence, 74 draft guidance statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. Conclusion These guidance statements, made in the context of limited clinical data, are intended to provide direction to rheumatology health care providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.

Objective Patients with rheumatoid arthritis (RA) in whom remission is achieved following combination therapy with methotrexate plus etanercept face an ongoing medication burden. This study was undertaken to investigate whether sustained remission achieved on combination therapy can be maintained with either methotrexate or etanercept monotherapy, as assessed following discontinuation of one or the other medication from the combination. Methods Of the 371 adult patients with RA who received combination therapy with methotrexate plus etanercept, remission (defined as a Simplified Disease Activity Index [SDAI] score of ≤3.3) was sustained in 253 patients through a 24‐week open‐label period. These 253 patients then entered a 48‐week, double‐blind period and were randomized to receive either 1) methotrexate monotherapy (n = 101), 2) etanercept monotherapy (n = 101), or 3) methotrexate plus etanercept combination therapy (n = 51). Patients who subsequently experienced disease‐worsening received rescue therapy with the combination regimen at the same dosages as used in the initial run‐in period. The primary end point was the proportion of patients in whom SDAI‐defined remission was maintained without disease‐worsening at week 48 in the etanercept monotherapy group as compared to the methotrexate monotherapy group. Secondary end points included time to disease‐worsening, and the proportion of patients in whom SDAI‐defined remission was recaptured after initiation of rescue therapy. Results Baseline demographic and clinical characteristics of the RA patients were similar across the treatment groups. At week 48, SDAI‐defined remission was maintained in significantly more patients in the etanercept monotherapy group than in the methotrexate monotherapy group (49.5% versus 28.7%; P = 0.004). Moreover, as a secondary end point, sustained SDAI‐defined remission was achieved in significantly more patients who received combination therapy than in those who received methotrexate monotherapy (52.9% versus 28.7%; P = 0.006). Time to disease‐worsening was shorter in those who received methotrexate monotherapy than in those who received etanercept monotherapy or those who received combination therapy (each P < 0.001 versus methotrexate monotherapy). Among the patients who received rescue therapy, SDAI‐defined remission was recaptured in 70–80% in each treatment group. No new safety signals were reported. Conclusion The efficacy of etanercept monotherapy was superior to that of methotrexate monotherapy and similar to that of combination therapy in maintaining remission in patients with RA. SDAI‐defined remission was recaptured in most of the patients who were given rescue therapy. These data could inform decision‐making when withdrawal of therapy is being considered to reduce treatment burden in patients with well‐controlled RA.

ObjectiveWe estimated meaningful change thresholds (MCTs) for Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue and Pain Interference in rheumatoid arthritis (RA).MethodsThe responsiveness of several patient-reported outcomes (PROs) was assessed among 521 patients with RA in the Arthritis, Rheumatism, and Aging Medical Information Systems (ARAMIS) cohort. PROMIS Fatigue (7-item) and Pain Interference (6-item) short form instruments were administered at baseline, 6 months, and 12 months. Self-reported retrospective changes over the previous 6 months (a lot better/worse, a little better/worse, stayed the same) were obtained at 6 and 12 months’ follow-up. We estimated MCTs using the mean change in PROMIS scores for patients who rated their change “a little better” or “a little worse.”ResultsBaseline fatigue and pain interference scores were near normal (median 54 and 56, respectively). At 6 months, 7.9% of patients reported their fatigue was a little better compared to baseline (mean change [SD]: –2.6 [4.8]) and 22.8% a little worse (1.7 [5.6]). Pain was a little better for 11.5% of patients (–1.9 [6.1]) and a little worse for 24.2% of patients (0.6 [5.7]). At 12 months, results were similar. Thus, the MCT range was 1–2 points for both fatigue and pain interference. Correlations between change scores and retrospective ratings were low (0.13–0.29), indicating possible underestimation of MCT.ConclusionThe group-level MCT for PROMIS Fatigue and Pain Interference is roughly 2–3 points and corresponds to a small effect size, which is consistent with earlier work demonstrating an MCT of 2 points for PROMIS Physical Functioning.

ObjectiveSome patients with rheumatoid arthritis (RA) who persist in remission may decide to stop their therapy. We evaluated baseline characteristics associated with remaining in remission or low disease activity (LDA) following medication withdrawal.MethodsSEAM-RA was a phase 3, multicenter, randomized withdrawal, double-blind, controlled study in patients with RA on methotrexate + etanercept. If remission (Simplified Disease Activity Index [SDAI] ≤3.3) was sustained through a 24-week run-in period, patients then entered a 48-week double-blind period and were randomized 2:2:1 to receive methotrexate monotherapy, etanercept monotherapy, or continue combination therapy. Multivariate logistic regression analysis was performed to identify baseline factors associated with remission or LDA at the end of both periods.ResultsOf 371 patients enrolled, 253 entered the double-blind period. After adjusting for other factors, covariates associated with achieving SDAI remission at the end of the run-in period included younger age, longer duration of methotrexate treatment, and less severe clinical disease parameters. Covariates associated with maintaining remission/LDA at the end of the 48-week double-blind period included lower Patient Global Assessment of Disease Activity (PtGA), lower C-reactive protein, rheumatoid factor (RF) negativity, longer RA duration in the methotrexate arm, shorter duration of etanercept treatment, and lower magnesium.ConclusionThese findings indicate patients with overall lower disease activity are more likely to remain in SDAI remission/LDA after switching from combination therapy to monotherapy. RF-negative status and lower PtGA scores were strongly associated with likelihood of remaining in remission/LDA with methotrexate or etanercept monotherapy.

Background Patient-reported outcomes (PROs) are increasingly used to track symptoms and to assess disease activity, quality of life, and treatment effectiveness. It is therefore important to understand which PROs patients with rheumatic and musculoskeletal disease consider most important to track for disease management. Methods Adult US patients within the ArthritisPower registry with ankylosing spondylitis, fibromyalgia syndrome, osteoarthritis, osteoporosis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus were invited to select between 3 and 10 PRO symptom measures they felt were important to digitally track for their condition via the ArthritisPower app. Over the next 3 months, participants (pts) were given the option to continue tracking their previously selected measures or to remove/add measures at 3 subsequent monthly time points (month [m] 1, m2, m3). At m3, pts prioritized up to 5 measures. Measures were rank-ordered, summed, and weighted based on pts rating to produce a summary score for each PRO measure. Results Among pts who completed initial selection of PRO assessments at baseline (N = 253), 140 pts confirmed or changed PRO selections across m1–3 within the specified monthly time window (28 days ± 7). PROs ranked as most important for tracking were PROMIS Fatigue, Physical Function, Pain Intensity, Pain Interference, Duration of Morning Joint Stiffness, and Sleep Disturbance. Patient’s preferences regarding the importance of these PROs were stable over time. Conclusion The symptoms that rheumatology patients prioritized for longitudinal tracking using a smartphone app were fatigue, physical function, pain, and morning joint stiffness.

Objective To determine the incidence of dementia in patients with rheumatoid arthritis (RA) 65 years and older, and compare the incidence of dementia in patients with RA with prevalent cardiovascular (CV) disease (CVD), CV risk factors but no prevalent CVD and neither (referent group). Methods We analyzed claims data from the Center for Medicare & Medicaid Services (CMS) from 2006–2014. Eligibility criteria included continuous medical and pharmacy coverage for ≥ 12 months (baseline period 2006), > 2 RA diagnoses by a rheumatologist and at least 1 medication for RA. CVD and CV risk factors were identified using codes from the Chronic Condition Data Warehouse. Incident dementia was defined by 1 inpatient or 2 outpatient claims, or one dementia specific medication. Age-adjusted incident rates were calculated within each age strata. Univariate and multivariate Cox proportional hazard models were used to calculate Hazard Ratios (HR) and 95% confidence intervals. Results Among 56,567 patients with RA, 11,789 (20.1%) incident cases of dementia were included in the main analysis. Age adjusted incident rates were high among all groups and increased with age. After adjustment for age, sex, comorbidities and baseline CV and RA medications, patients with CVD and CV risk factors between 65 and 74 years had an increased risk for incident dementia compared to those without CVD and without CV risk factors (HR 1.18 (95% CI 1.04–1.33) and HR 1.03 (95% CI 1.00–1.11), respectively). We observed a trend towards increased risk in patients between 75 and 84 years with CVD at baseline. Conclusion Patients with RA with both CVD and CV risk factors alone are at an increased risk for dementia compared to those with neither CVD nor CV risk factors; however, this risk is attenuated with increasing age. The impact of RA treatment and CV primary prevention strategies in the prevention of dementia in patients with RA warrants further studies.

BackgroundRheumatoid arthritis (RA) patients have increased risk for cardiovascular disease (CVD). Accurate CVD risk prediction could improve care for RA patients. Our goal is to develop and validate a biomarker-based model for predicting CVD risk in RA patients.MethodsMedicare claims data were linked to multi-biomarker disease activity (MBDA) test results to create an RA patient cohort with age ≥ 40 years that was split 2:1 for training and internal validation. Clinical and RA-related variables, MBDA score, and its 12 biomarkers were evaluated as predictors of a composite CVD outcome: myocardial infarction (MI), stroke, or fatal CVD within 3 years. Model building used Cox proportional hazard regression with backward elimination. The final MBDA-based CVD risk score was internally validated and compared to four clinical CVD risk prediction models.Results30,751 RA patients (904 CVD events) were analyzed. Covariates in the final MBDA-based CVD risk score were age, diabetes, hypertension, tobacco use, history of CVD (excluding MI/stroke), MBDA score, leptin, MMP-3 and TNF-R1. In internal validation, the MBDA-based CVD risk score was a strong predictor of 3-year risk for a CVD event, with hazard ratio (95% CI) of 2.89 (2.46–3.41). The predicted 3-year CVD risk was low for 9.4% of patients, borderline for 10.2%, intermediate for 52.2%, and high for 28.2%.Model fit was good, with mean predicted versus observed 3-year CVD risks of 4.5% versus 4.4%. The MBDA-based CVD risk score significantly improved risk discrimination by the likelihood ratio test, compared to four clinical models. The risk score also improved prediction, reclassifying 42% of patients versus the simplest clinical model (age + sex), with a net reclassification index (NRI) (95% CI) of 0.19 (0.10–0.27); and 28% of patients versus the most comprehensive clinical model (age + sex + diabetes + hypertension + tobacco use + history of CVD + CRP), with an NRI of 0.07 (0.001–0.13). C-index was 0.715 versus 0.661 to 0.696 for the four clinical models.ConclusionA prognostic score has been developed to predict 3-year CVD risk for RA patients by using clinical data, three serum biomarkers and the MBDA score. In internal validation, it had good accuracy and outperformed clinical models with and without CRP. The MBDA-based CVD risk prediction score may improve RA patient care by offering a risk stratification tool that incorporates the effect of RA inflammation.

Objective This study aimed to analyze the concerns and health-related behaviors in patients with vasculitis during the early phase of the coronavirus disease 2019 (COVID-19) pandemic in North America. Methods Patients with vasculitis in North America were invited to complete an online survey through the Vasculitis Patient-Powered Research Network in collaboration with the Vasculitis Foundation and the Relapsing Polychondritis Foundation. Questions focused on concerns and behaviors related to doctors' visits, tests, medication, and telehealth use. Factors affecting their concern and health-related behaviors were determined. Results Data from 662 patients were included: 90% of patients were White, 78% were women, 83% expressed moderate or high levels of concern about COVID-19, and 87% reported that their vasculitis moderately or extremely affected their level of concern. Older age, female sex, lung disease, and immunosuppression were associated with greater concern. Doctors' visits, laboratory tests, and other tests were avoided by 66%, 46%, and 40% of patients, respectively. Younger age, urban location, higher income, higher concern levels, and prednisone use (>10 mg/day) were associated with greater likelihood of avoiding visits or tests. Ten percent of patients on immunosuppressive therapy stopped their medication. Twenty-nine percent patients on rituximab avoided an infusion. Forty-four percent of patients had telehealth visits; more visits were reported for younger patients, for patients on glucocorticoids, and in Canada versus the United States. Conclusion During the COVID-19 pandemic, patients with vasculitis have high levels of concern and exhibit potentially harmful health-related behaviors. Health care use varies across different demographic groups and geographic regions. Specific strategies are warranted to facilitate engagement of these patients with the health care system during the pandemic.

To provide guidance to rheumatology providers on the use of COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases (RMDs).A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9-point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings.Despite a paucity of direct evidence, statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines, including supplemental/booster dosing, in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination.These guidance statements are intended to provide direction to rheumatology health care providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.