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The effect of the COVID-19 pandemic on community-based rheumatology care and the use of telehealth is unclear. We undertook this study to investigate the impact of the pandemic on rheumatology care delivery in a large community practice-based network.Using a community practice-based rheumatologist network, we examined trends in in-person versus telehealth visits versus canceled visits in 3 time periods: pre-COVID-19, COVID-19 transition (6 weeks beginning March 23, 2020), and post-COVID-19 transition (May-August). In the transition period, we compared patients who received in-person care versus telehealth visits versus those who cancelled all visits. We used multivariable logistic regression to identify factors associated with canceled or telehealth visits.Pre-COVID-19, there were 7,075 visits/week among 60,002 unique rheumatology patients cared for by ~300 providers practicing in 92 offices. This number decreased substantially (24.6% reduction) during the COVID-19 transition period for in-person visits but rebounded to pre-COVID-19 levels during the post-COVID-19 transition. There were almost no telehealth visits pre-COVID-19, but telehealth increased substantially during the COVID-19 transition (41.4% of all follow-up visits) and slightly decreased during the post-COVID-19 transition (27.7% of visits). Older age, female sex, Black or Hispanic race/ethnicity, lower socioeconomic status, and rural residence were associated with a greater likelihood of canceling visits. Most factors were also associated with a lower likelihood of having telehealth versus in-office visits. Patients living further from the rheumatologists' office were more likely to use telehealth.COVID-19 led to large disruptions in rheumatology care; these disruptions were only partially offset by increases in telehealth use and disproportionately affected racial/ethnic minorities and patients with lower socioeconomic status. During the COVID-19 era, telehealth continues to be an important part of rheumatology practice, but disparities in access to care exist for some vulnerable groups.

Background Although previous studies suggested that rituximab increases the risk of Pneumocystis jirovecii pneumonia (PJP), it is uncertain whether its primary prophylaxis for PJP is justified. Research Question Does the benefit of primary prophylaxis for PJP in patients receiving rituximab treatment outweigh the potential risk of the prophylaxis? Study Design and Methods This retrospective study included 3524 patients (hematologic diseases=2500; rheumatic diseases=559; pre/post-solid organ transplantation=465) first exposed to rituximab between 2002 and 2018 in a tertiary referral center in South Korea. Patients were classified into a control group (n=2523) and a prophylaxis group (n=1001) according to the administration of prophylactic TMP-SMX during the first 28 days after the start of rituximab (intention-to-treat analysis). In addition, exposure to TMP-SMX was examined as a time-varying variable (time-varying analysis). Primary outcome was the prophylactic effect of TMP-SMX on the 1-year incidence of PJP. Inverse probability of treatment weights was applied to minimize the baseline imbalance. Secondary outcome included the incidence of adverse drug reactions (ADRs) related to TMP-SMX. Results Over 2759.9 person-years, 92 PJP infections occurred, with a mortality rate of 27.2%. The prophylaxis group showed a significantly lower incidence of PJP (adjusted sub-distribution hazard ratio (aSHR), 0.20 [95% CI, 0.10–0.42]) than the control group. This result was consistent with the results of time-varying analysis, in which only one PJP infection occurred during TMP-SMX administration (aSHR, 0.01 [0.003–0.16]). The incidence of adverse drug reactions (ADRs) related to TMP-SMX was 18.1 (14.6–22.2)/100 person-years, and most were of mild-to-moderate severity. Based on ten severe ADRs, the number needed to harm was 101 (61.9–261.1), whereas the number needed to prevent one PJP infection was 32 (24.8–39.4). Interpretation TMP-SMX prophylaxis significantly reduces PJP incidence with a tolerable safety profile in patients receiving rituximab treatment.

ObjectivesRheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals.MethodsPatients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year.Results19 902 patients met criteria. 1106 CVE occurred (1.66/100 person-years). Increased aHR occurred at current doses of ≥5–9 mg 1.56 (1.18–2.06) and ≥10 mg 1.91 (1.31–2.79), without increased risk at 0–4 mg 1.04 (0.55–1.59). Cumulative dose over preceding 6 months showed increased aHR at 751–1100 mg 1.43 (1.04–1.98) and >1100 mg 2.05 (1.42–2.94), without increased risk at lower doses; duration of use over preceding 6 months exhibited increased aHR for >81 days of use 1.54 (1.08–2.32), without increased risk at shorter durations. One-year analyses were consistent.ConclusionsOver preceding 6-month and 1-year intervals, initiating glucocorticoids in steroid-naïve RA patients is associated with increased risk of CVE at daily doses ≥5 mg and increased cumulative dose and duration of use. No association with risk for CVE was found with daily prednisone of ≤4 mg or shorter cumulative doses and durations.

ObjectiveTo quantify comparative effectiveness of interleukin (IL)−12/23 antagonist (ustekinumab), IL-17A antagonists (secukinumab and ixekizumab), PDE4 inhibitor (apremilast) and tumour necrosis factor-alpha (TNF-α) inhibitors (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) for psoriatic arthritis (PsA).MethodsWe adapted a deidentified claims-based algorithm validated for inflammatory arthritis treatments to compare treatments among a retrospective cohort of commercially insured and Medicare Advantage beneficiaries with PsA from October 2013 to April 2019 in the OptumLabs Data Warehouse. Main outcomes include (1) treatment effectiveness, based on: adherence, adding or switching biologic or PDE4, addition of new non-biologic disease-modifying antirheumatic drug, increase in biologic or PDE4 dose or frequency and glucocorticoid use and (2) percentage of each group fulfilling the effectiveness algorithm. We used Poisson regression with robust variance stratified by prior PsA biologic exposure and adjusted for potential confounders.ResultsOf 2730 individuals with PsA, 327 received IL-12/23, 138 IL-17A’s, 624 PDE4 and 1641 TNF-α’s. Effectiveness criteria were fulfilled among 63 (19.3%) IL-12/23 recipients, 40 (29.0%) IL-17A recipients, 160 (25.6%) PDE4 recipients and 530 (32.3%) TNF-α recipients. Among biologic-naïve individuals, IL-12/23 was less effective than TNF-α’s with fully adjusted relative risk (aRR) compared with TNF-α’s of 0.63 (95% CI 0.45 to 0.89). Among biologic-experienced individuals, PDE4 recipients were less effective than TNF-α’s (aRR 0.67, 95% CI 0.46 to 0.96).ConclusionsTNF-α’s appeared more effective than IL-12/23’s for biologic-naïve individuals, and PDE4’s for biologic-experienced individuals. These results may help inform treatment choice for individuals with PsA.

In rheumatoid arthritis (RA), respiratory manifestations include chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). We assessed whether baseline COPD and smoking were associated with RA-ILD onset.We identified new-onset ILD in incident RA subjects within the MarketScan Commercial Claims database, using physician and/or hospitalisation diagnostic codes. Smoking data (current, past, never) were available for a subset via a health questionnaire. Kaplan-Meier analyses assessed time to ILD onset, stratified by prior COPD and smoking. Multivariate Cox regression models were adjusted for age, sex, and (in the subset) smoking. Sensitivity analyses adjusted for past RA drugs.Among 373,940 new RA subjects, 6343 (1.7%) developed ILD (8.1 events per 1000 person-year, 95% CI 7.9, 8.3). ILD was more common among subjects with baseline COPD. Adjusting for age and sex, the hazard ratio (HR) between baseline COPD and incident ILD was 2.15, 95% CI 1.93, 2.39. We could not establish a clear relationship between current smoking and ILD; in the subset with smoking data, the HR point estimate for COPD was similar but the 95% CI was wider (due to fewer subjects) and included the null value. Adjusting for baseline RA drugs did not change results.Pre-existing COPD in incident RA subjects was associated with higher risk of future ILD. While a trend persisted after adjusting for smoking, we were limited by reduced sample size. Our study highlights the importance of ongoing assessments of potentially complicated relationships between smoking, COPD, and other factors in RA-associated ILD.

OBJECTIVE Comparative effectiveness research can inform treatment decisions regarding the choice of biologics for rheumatoid arthritis (RA). The objective of this study is to compare the efficacy of tumor necrosis factor inhibitors (TNFis) and non-TNFis (nTNFis) in real-world patients with RA and past TNFi experience. METHODS Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) was nested within the United States Corrona registry. Adult patients with RA with moderate to high disease activity (Clinical Disease Activity Index [CDAI] >10) with exposure to one or more prior TNFis who were switching to a new TNFi or nTNFi (choice of therapy per physician choice) were enrolled. The primary outcome was the achievement of low disease activity (LDA) at 12 months (CDAI ≤10; disease activity score in 28 joints based on C-reactive protein [DAS28-CRP]

In rheumatoid arthritis, time spent using ineffective medications may lead to irreversible disease progression. Despite availability of targeted treatments, only a minority of patients achieve sustained remission, and little evidence exists to direct the choice of biologic disease-modifying antirheumatic drugs in individual patients. Machine learning was used to identify a rule to predict the response to sarilumab and discriminate between responses to sarilumab versus adalimumab, with a focus on clinically feasible blood biomarkers. The decision tree model GUIDE was trained using a data subset from the sarilumab trial with the most biomarker data, MOBILITY, to identify a rule to predict disease activity after sarilumab 200 mg. The training set comprised 18 categorical and 24 continuous baseline variables; some data were omitted from training and used for validation by the algorithm (cross-validation). The rule was tested using full datasets from four trials (MOBILITY, MONARCH, TARGET, and ASCERTAIN), focusing on the recommended sarilumab dose of 200 mg. In the training set, the presence of anti-cyclic citrullinated peptide antibodies, combined with C-reactive protein > 12.3 mg/l, was identified as the “rule” that predicts American College of Rheumatology 20% response (ACR20) to sarilumab. In testing, the rule reliably predicted response to sarilumab in MOBILITY, MONARCH, and ASCERTAIN for many efficacy parameters (e.g., ACR70 and the 28-joint disease activity score using CRP [DAS28-CRP] remission). The rule applied less to TARGET, which recruited individuals refractory to tumor necrosis factor inhibitors. The potential clinical benefit of the rule was highlighted in a clinical scenario based on MONARCH data, which found that increased ACR70 rates could be achieved by treating either rule-positive patients with sarilumab or rule-negative patients with adalimumab. Well-established and clinically feasible blood biomarkers can guide individual treatment choice. Real-world validation of the rule identified in this post hoc analysis is merited. NCT01061736, NCT02332590, NCT01709578, NCT01768572.

Incidence proportions of hospitalization, intensive care unit admission, in-hospital death, all-cause mortality, and clinical manifestations of interest were calculated. Baseline Characteristics and IPs of Clinical Manifestations/Outcomes in the RA, PsA, UC, and Comparator Cohorts. a.At least 1 diagnosis of RA, PsA, or UC, and treatment with IM therapy (JAK inhibitor, TNFi, non-TNFi biologic, or csDMARD) within 2 yrs prior to SARS-CoV-2 diagnosis date;b.Absence of a diagnosis of RA, PsA, or UC, and no treatment with IM therapy within 2 yrs prior to SARS-CoV-2 diagnosis date;c.Baseline was defined as within 6 months prior to SARS-CoV-2 diagnosis date;d.csDMARDs included auranofin, aurothioglucose, azathioprine, chloroquine hydrochloride, chloroquine phosphate, cyclophosphamide, cyclosporine, gold sodium thiomalate, hydroxychloroquine sulfate, leflunomide, mercaptopurine, mesalamine, methotrexate, minocycline hydrochloride, n-acetylpenicillamine, penicillamine, primaquine, sulfasalazine, tacrolimus, and thalidomide;e.Within 90 days prior to SARS-CoV-2 diagnosis date;f.Denominator is the number of pts hospitalized within 30 days of SARS-CoV-2 diagnosis;defined as death during hospitalization;g.Within 90 days of SARS-CoV-2 diagnosis date;h.Within 30 days of SARS-CoV-2 diagnosis date. ARDS, acute respiratory distress syndrome;CI, confidence interval;csDMARD, conventional synthetic disease-modifying antirheumatic drug;ECMO, extracorporeal membrane oxygenation;ICU, intensive care unit;IM, immunomodulatory;IP, incidence proportion;IV, intravenous;JAK, Janus kinase;N, number of pts in the cohort;n, number of pts in the specified category;PsA, psoriatic arthritis;pts, patients;RA, rheumatoid arthritis;TNFi, tumor necrosis factor inhibitor;UC, ulcerative colitis.

Background & Aims This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. Methods Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC 50% among those with baseline FC >250 μg/g) and C-reactive protein (CRP) response (high-sensitivity CRP 50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). Results The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). Conclusions The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679

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 The objective of this study was to investigate the diagnostic prevalence of ankylosing spondylitis (AS) and axial spondyloarthritis (axSpA) in the United States and examine treatment patterns for these diseases. Methods This retrospective observational cohort study drew from 2006-2014 data in the US Medicare Fee-for-Service and IBM MarketScan databases. AS and axSpA diagnoses were identified through International Classification of Diseases, Ninth Revision [ICD-9] codes. Diagnostic prevalence (per 10,000 patients) was calculated as patients with AS and axSpA with full insurance coverage in each calendar year divided by the total patients with full insurance coverage in the same year. Two diagnosis definitions were used: definition 1 (D1), one or more relevant ICD-9 codes from hospital claims or two or more relevant ICD-9 codes from outpatient claims; definition 2 (D2), one or more codes from hospital/outpatient claims. Primary analyses assessed annual AS and axSpA prevalence (D1); sensitivity analyses assessed annual (D2) and 2-year prevalence. Patterns in prevalence and treatment use were analyzed descriptively; no statistical tests were performed. Results An increase in AS prevalence (per 10,000 patients) was seen from 2006 to 2014 in primary analyses (Medicare: 2.12-3.60; MarketScan: 0.85-1.42) and sensitivity analyses. A similar trend occurred for axSpA (Medicare: 4.39-6.52; MarketScan: 1.33-2.21). For Medicare, the proportion of patients with AS (D1) using tumor necrosis factor α inhibitors (TNFis), conventional synthetic antirheumatic drugs (csARDs), nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and glucocorticoids remained relatively stable; for MarketScan, TNFi-treated patients increased (51.7% to 65.7%) and NSAID-treated patients decreased (63.5% to 55.7%). Conclusion AS and axSpA prevalence may have increased in the United States between 2006 and 2014. Reasons are unknown, but this may be due to increased disease awareness, among other factors.

Objective.The management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) has evolved substantially over the last 2 decades. We sought to characterize AAV treatment patterns in the United States.Methods.We identified patients with AAV in the Rheumatology Informatics System for Effectiveness (RISE) registry who had at least 2 rheumatology clinician visits between January 1, 2015, and December 31, 2017. Demographics, medications, laboratory test results, and billing codes were extracted from the medical record. Demographic and prescription trends were assessed overall and across US regions.Results.We identified 1462 patients with AAV, 259 (18%) with new or relapsing AAV. The majority were classified as having granulomatosis with polyangiitis (75%). The mean age was 59.8 years and 59% were female. The majority of patients were in the South (45%) followed by the Mid-West (32%), West (12%), and Northeast (8%). Patients had a median of 3 visits and follow-up of 579 days. The most commonly prescribed medications during the study period were glucocorticoids (86%) followed by rituximab (45%), methotrexate (33%), azathioprine (32%), and mycophenolate mofetil (18%); cyclophosphamide (CYC) was rarely used (7%). At the most recent visits in RISE, 47% of patients were on glucocorticoids. Prescription trends were similar across regions.Conclusion.To our knowledge, this is the first study to evaluate the demographics and management of AAV by rheumatologists outside of major referral centers. Management strategies vary widely, but CYC is rarely used. These observations can be used to inform future research priorities. Additional studies are needed to characterize AAV severity in RISE as well as patient and provider treatment preferences.

International audience; Objective: To investigate the impact of baseline and time-varying factors on the risk of serious adverse events (SAEs) in patients during long-term certolizumab pegol (CZP) treatment.Methods: Safety data were pooled across 34 CZP clinical trials in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PSO). Cox proportional hazards modeling was used to investigate the association of baseline patient characteristics with risk of serious infectious events (SIEs), malignancies, and major adverse cardiac events (MACEs). Cox modeling for recurrent events assessed the impact of time-varying body mass index (BMI), systemic corticosteroid (CS) use, and disease activity on SIE risk in RA and SAE risk in PSO.Results: Data were pooled from 8747 CZP-treated patients across indications. Cox models reported a 44% increase in SIE risk associated with a baseline BMI of 35 kg/m2 or more versus a baseline BMI of 18.5 kg/m2 to less than 25 kg/m2 . Baseline systemic CS use, age of 65 years or more, and disease duration of 10 years or longer also increased SIE risk. Older age was the only identified risk factor for malignancies. The risk of MACEs increased 107% for BMI of 35 kg/m2 or more versus BMI of 18.5 kg/m2 to less than 25 kg/m2 and increased 51% for men versus women. Higher disease activity, older age, systemic CS use, BMI of 35 kg/m2 or more, and baseline comorbidities were SIE risk factors in RA. Age and systemic CS use were risk factors for SAEs in PSO.Conclusion: Age, BMI, systemic CS use, and disease activity were identified as SIE risk factors in CZP-treated patients. Risk of malignancies was greater in older patients, whereas obesity and male sex were MACE risk factors.

Background The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors. Methods Four cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression. Results Univariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from Conclusion The adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI.

Rheumatoid arthritis (RA) is a systemic and incurable autoimmune disease characterized by chronic inflammation in synovial lining of joints. To identify the signaling pathways involved in RA, its disease activity, and treatment response, we adapted a systems immunology approach to simultaneously quantify 42 signaling nodes in 21 immune cell subsets (e.g., IFNα→p-STAT5 in B cells) in peripheral blood mononuclear cells (PBMC) from 194 patients with longstanding RA (including 98 patients before and after treatment), and 41 healthy controls (HC). We found multiple differences between patients with RA compared to HC, predominantly in cytokine-induced Jak/STAT signaling in many immune cell subsets, suggesting pathways that may be associated with susceptibility to RA. We also found that high RA disease activity, compared to low disease activity, was associated with decreased (e.g., IFNα→p-STAT5, IL-10→p-STAT1) or increased (e.g., IL-6→STAT3) response to stimuli in multiple cell subsets. Finally, we compared signaling in patients with established, refractory RA before and six months after initiation of methotrexate (MTX) or TNF inhibitors (TNFi). We noted significant changes from pre-treatment to post-treatment in IFNα→p-STAT5 signaling and IL-10→p-STAT1 signaling in multiple cell subsets; these changes brought the aberrant RA signaling profiles toward those of HC. This large, comprehensive functional signaling pathway study provides novel insights into the pathogenesis of RA and shows the potential of quantification of cytokine-induced signaling as a biomarker of disease activity or treatment response.

ObjectiveTofacitinib is an oral Janus kinase for the treatment of rheumatoid arthritis (RA). This post hoc analysis assessed whether baseline body mass index (BMI) impacts tofacitinib efficacy in patients with RA.MethodsPooled data from six phase 3 studies in patients receiving tofacitinib 5 mg (N=1589) or 10 mg (N=1611) twice daily or placebo (advancing to active treatment at months 3 or 6; N=680), ±conventional synthetic disease-modifying antirheumatic drugs, were stratified by baseline BMI (2). Endpoints (through to month 6) were assessed descriptively: American College of Rheumatology 20/50/70 response rates; changes from baseline (∆) in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), DAS28-4(C-reactive protein), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI) and pain; and proportions of patients achieving DAS28-4(ESR) ≥1.2 and HAQ-DI ≥0.22 decreases from baseline, low disease activity (DAS28-4(ESR) ≤3.2 or CDAI ≤10) and radiographic non-progression (Δmodified Total Sharp Score ≤0.5; months 12 and 24). Estimates were adjusted using multivariable models for selected outcomes. Univariate/multivariable regression analyses determined predictors of month 6 outcomes.ResultsOf 3880 patients included, 1690 (43.6%), 1173 (30.2%) and 1017 (26.2%) had baseline BMI 2, respectively. Tofacitinib showed greater efficacy improvements versus placebo in each BMI category. Differences in efficacy outcomes (adjusted and unadjusted) were generally not clinically meaningful across BMI categories within treatment groups. In regression analyses, BMI was not consistently associated with selected outcomes.ConclusionsBaseline BMI did not consistently affect tofacitinib response suggesting that tofacitinib is an effective oral treatment option for adults with moderate to severe RA regardless of baseline BMI, including patients with BMI ≥30 kg/m2.Trial registration numbersNCT00814307, NCT01039688; NCT00960440; NCT00847613; NCT00856544; NCT00853385.

We appreciate the letter by Mortezavi et. al. describing vaccine response and the frequency of disease worsening in patients receiving tofacitinib. The ACR COVID Vaccine Guidance Task Force was aware of the two studies cited and appreciate their summary of the results. We would point out that in the rheumatoid arthritis study by Winthrop et. al., patients receiving tofacitinib in Study A had a lower likelihood of a satisfactory response to pneumococcal vaccination (45.1%) compared to placebo‐treated patients (68.4%), a difference of 23.3%, 95% CI −36.6 to −9.6%. The differences were numerically even larger for patients receiving concomitant tofacitinib and methotrexate (31.6% of patients with a satisfactory response, difference of −30.2%, 95% CI −47.3 to −11.4%) compared to methotrexate monotherapy.

Objective.Patients with rheumatoid arthritis (RA) who also have diabetes mellitus (DM) might have worse clinical outcomes and adverse events compared to patients with RA who do not have DM. We evaluated the effects of DM on Health Assessment Questionnaire (HAQ) changes and outpatient infection rates in patients with RA.Methods.Using the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness (RISE) electronic health record–based registry, we identified patients with RA who had ≥ 1 rheumatologist visit with a HAQ measured in 2016 (index visit), ≥ 1 previous visit, and a subsequent outcome visit with the same HAQ measured at 12 months (± 3 months). We identified DM by diagnosis codes, medications, or laboratory values. Outpatient infection was defined by diagnosis codes or antiinfective medications. We calculated mean HAQ change and incidence rate (IR) of outpatient infections among patients with and without DM. Generalized linear models and Cox regression were used to calculate the adjusted mean HAQ change and HRs.Results.We identified 3853 RA patients with DM and 18,487 without DM. The mean HAQ change between index and outcome visit among patients with DM was 0.03 and without DM was 0.002 (P < 0.01). We identified 761 outpatient infections for patients with DM with an IR of 22.6 (95% CI 21.0–24.2) per 100 person-years and 3239 among patients without DM with an IR of 19.8 (95% CI 19.1–20.5). The adjusted HR of outpatient infections among patients with DM was 0.99 (95% CI 0.91–1.07), compared to patients without DM.Conclusion.Patients with RA with concomitant DM had greater worsening, or less improvement, in their functional status, suggesting additional interventions may be needed for RA patients with DM to optimize treatment and management of other comorbidities.

IntroductionBronchiectasis is an increasingly common chronic inflammatory airway disease. We evaluated secondary safety outcomes in a comparative effectiveness study of chronic inhaled corticosteroids (ICS) and macrolide monotherapy in bronchiectasis patients.MethodsWe conducted a retrospective study using US Medicare Parts A, B and D (but not C) 2006–2014 datasets. Among those with a pulmonologist-associated bronchiectasis claim (ICD-9-CM 494.0 or 494.1), without cystic fibrosis, we identified the first new use of either chronic (>28 days) ICS or macrolide monotherapy. For each drug exposure, we calculated crude incidence rates of the secondary safety outcomes: arrhythmia, myocardial infarction, sensorineural hearing loss, hip fracture and opportunistic infections. We calculated a propensity score (PS) for ICS use using demographic, clinical and utilisation characteristics and compared risks of macrolides versus ICS for each outcome using PS decile-adjusted Cox regression models.ResultsOf 285 043 Medicare patients with bronchiectasis, we identified 6500 (2%) macrolide and 83 589 (29%) ICS new users. Key covariates were balanced across exposure groups within decile. Myocardial infarction, hip fracture and opportunistic infection were not significantly associated with treatment. Macrolides were associated with a decreased risk of arrhythmia (adjusted hazard ratio (aHR) 0.87, 95% CI 0.80–0.94) and an increased risk of sensorineural hearing loss (aHR 1.38, 95% CI 1.56–1.22) compared to ICS.ConclusionsMacrolides were not associated with an elevated risk of acute cardiac events compared to ICS. The increased risk of hearing loss in macrolide users compared to ICS users in older bronchiectasis patients should be balanced against known benefits of macrolides.

ObjectiveTo assess concerns and healthcare-related behaviors of patients with autoimmune rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic.MethodsAdults from the United States with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE) from the ArthritisPower Patient-Powered Research Network and CreakyJoints patient community completed surveys. Concerns and behaviors were compared among patients with different autoimmune conditions, disease-modifying antirheumatic drug (DMARD) use, and geographic measures of urban status, income, education, and COVID-19 activity.ResultsAmong 1517 participants (925 RA, 299 PsA, 185 AS, 108 SLE), mean age was 55.1 years, 88.3% were female, and 89.5% were White. COVID-19 concerns were similar across the country and were higher in biologic users (P < 0.001). Avoidance of doctor’s office visits (56.6%) or laboratory testing (42.3%) and use of telehealth (29.5%) were more common in urban areas. Among participants receiving a DMARD without COVID-19 or other respiratory illness, 14.9% stopped a DMARD, with 78.7% of DMARD interruptions not recommended by a physician. DMARD stopping was more common in participants with lower socioeconomic status (SES) and in participants who avoided an office visit (OR 1.46, 95% CI 1.04–2.04) or reported lack of telehealth availability OR 2.26 (95% CI 1.25–4.08).ConclusionIn the early months of the COVID-19 pandemic, patients with RA, PsA, AS, and SLE frequently avoided office visits and laboratory testing. DMARD interruptions commonly occurred without the advice of a physician and were associated with SES, office visits, and telehealth availability, highlighting the need for adequate healthcare access and attention to vulnerable populations during the pandemic.

PURPOSE: We assessed the impact of adjustment of the multi-biomarker disease activity score (MBDA) for age, sex, and leptin, over the range of age and adiposity, and assessed relationships with clinical disease activity. METHODS: Patients with RA, ages 18–75 years, were recruited from clinical practices and completed whole-body DXA to quantify fat mass indices (FMI, kg/m(2)). FMI Z-scores were calculated based on distributions in a reference population. Descriptive statistics described relationships between age, FMI Z-score, and the original MBDA and adjusted MBDA (aMBDA). Swollen joint counts (SJC) and the clinical disease activity index (CDAI) were assessed over MBDA categories. RESULTS: There were 104 participants (50% female) with mean (SD) age of 56.1 (12.5) and body mass index (BMI) of 28.8 (6.9). Older age was associated with higher MBDA scores in men. The aMBDA was not associated with age. The original MBDA score was associated with FMI Z-score among women (Rho = 0.42, p = 0.002) but not men. The aMBDA was not associated with FMI Z-score in either women or men. The aMBDA score was lower than the original MBDA in the highest quartile of FMI in women and was higher in the lowest FMI quartiles in women and men. CDAI, SJC, and radiographic scores were similar across activity categories for the original MBDA score and aMBDA. CONCLUSIONS: The aMBDA demonstrated reduced associations with adiposity, particularly among women. The aMBDA may be less likely to overestimate disease activity in women with greater adiposity and to underestimate disease activity in men and women with lesser adiposity.

Rheumatoid arthritis (RA) is chronic, painful, disabling condition resulting in significant impairments in physical, emotional, and social health. Our objective was to use different methods and perspectives to evaluate the responsiveness of Patient-Reported Outcomes Measurement Information System (PROMIS) short forms (SFs) and to identify minimal and meaningful score changes.Adults with RA who were enrolled in a multisite prospective observational cohort completed PROMIS physical function, pain interference, fatigue, and participation in social roles/activities SFs, the PROMIS 29-item form (PROMIS-29), and pain and patient global assessment, and rated change in specific symptoms and RA (a little versus lot better or worse) at the second visit. Physicians recorded joint counts, physician global assessment, and change in RA at visit 2. We compared mean score differences for minimal and meaningful improvement/worsening using patient and physician change ratings and distribution-based methods, and we visually inspected empirical cumulative distribution function curves by change categories.The 348 adults were mostly female (81%) with longstanding RA. Using patient ratings, generally 1-3-point differences were observed for minimal change and 3-7 points for meaningful change. Larger differences were observed with patient versus physician ratings and for symptom-specific versus RA change. Mean differences were similar among SF versions. Prespecified hypotheses about change in PROMIS physical function, pain interference, fatigue, and participation and legacy scales were supported.PROMIS SFs and the PROMIS-29 profiles are responsive to change and generally distinguish between minimal and meaningful improvement and worsening in key RA domains. These data add to a growing body of evidence demonstrating the robust psychometric properties of PROMIS and supporting its use in RA care, research, and decision-making.

ObjectiveTofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). We report the largest integrated safety analysis of tofacitinib, as of March 2017, using data from phase I, II, III, IIIb/IV and long-term extension studies in adult patients with RA.MethodsData were pooled for patients with RA who received ≥1 tofacitinib dose. Incidence rates (IRs; patients with events/100 patient-years [PY]; 95% CIs) of first-time occurrences were obtained for adverse events (AEs) of interest.Results7061 patients received tofacitinib (total exposure: 22 875 PY; median [range] exposure: 3.1 [0 to 9.6] years). IRs (95% CI) for serious AEs, serious infections, herpes zoster (all), opportunistic infections (excluding tuberculosis [TB]) and TB were 9.0 (8.6 to 9.4), 2.5 (2.3 to 2.7), 3.6 (3.4 to 3.9), 0.4 (0.3 to 0.5) and 0.2 (0.1 to 0.2), respectively. IRs (95% CI) for malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC and lymphomas were 0.8 (0.7 to 0.9), 0.6 (0.5 to 0.7) and 0.1 (0.0 to 0.1), respectively. IRs (95% CI) for gastrointestinal perforations, deep vein thrombosis, pulmonary embolism, venous thromboembolism, arterial thromboembolism and major adverse cardiovascular events were 0.1 (0.1 to 0.2), 0.2 (0.1 to 0.2), 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.3), 0.4 (0.3 to 0.5) and 0.4 (0.3 to 0.5), respectively. IR (95% CI) for mortality was 0.3 (0.2 to 0.3). IRs generally remained consistent across 6-month intervals to >78 months.ConclusionThis represents the largest clinical dataset for a JAK inhibitor in RA to date. IRs remained consistent with previous reports from the tofacitinib RA clinical development programme, and stable over time.Trial registration numbersNCT01262118;NCT01484561;NCT00147498;NCT00413660;NCT00550446;NCT00603512;NCT00687193;NCT01164579;NCT00976599;NCT01059864;NCT01359150;NCT02147587;NCT00960440;NCT00847613;NCT00814307;NCT00856544;NCT00853385;NCT01039688;NCT02187055;NCT00413699;NCT00661661.For summary of phase I, phase II, phase III, phase IIIb/IV and LTE studies included in the integrated safety analysis, see online supplemental table 1.

Objective.Methotrexate (MTX) has been associated with reduced risk for cardiovascular disease (CVD) events among patients with rheumatoid arthritis (RA) not exposed to biologic disease-modifying antirheumatic drugs (bDMARDs). The effect of concomitant MTX on CVD risk among RA patients initiating bDMARDs remains unknown.Methods.A retrospective cohort study was conducted to assess the effect of MTX on CVD risk using 2006–2015 Medicare claims data for patients with RA initiating bDMARD. The main exposure was current use of MTX, updated in a time-varying fashion. The primary outcome was a composite of incident myocardial infarction (MI), stroke, and fatal CVD. Secondary outcomes were each event that comprised the primary outcome. Incidence rates (IR) and 95% CI were calculated using Poisson regression. Associations between MTX and risk of CVD were assessed using Cox regression.Results.A total of 88,255 bDMARD initiations and 1861 CVD events were included in this study. Mean age was 64.6 (12.3) years, 84.0% were female, and 68.2% were non-Hispanic White. The crude IRs (95% CI) for CVD were 17.9 (16.9–18.8) and 12.1 (11.1–13.2) per 1000 patient-years among MTX unexposed and exposed, respectively. The multivariable adjusted HR (95% CI) for CVD events associated with MTX was 0.76 (0.68–0.85). Multivariable adjusted HRs were 0.78 (0.66–0.91), 0.74 (0.62–0.88), 0.77 (0.68–0.86), and 0.82 (0.73–0.93) for MI, stroke, MI or stroke, and a composite CVD outcome, respectively. Results were robust in sensitivity and subgroup analyses.Conclusion.Among patients with RA receiving biologics, concomitant MTX use was associated with a 24% lower risk for CVD events.

BACKGROUND Low-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain. OBJECTIVE To quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy. DESIGN Retrospective cohort study. SETTING Medicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015. PATIENTS Adults with RA receiving a stable DMARD regimen for more than 6 months. MEASUREMENTS Associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models. RESULTS 247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). The 1-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0% versus 5.2% (CI, 4.7% to 5.8%) for glucocorticoid dose of 5 mg or less per day, 8.1% (CI, 7.0% to 9.3%) for greater than 5 to 10 mg/d, and 10.6% (CI, 8.5% to 13.2%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). LIMITATION Potential for residual confounding and misclassification of glucocorticoid dose. CONCLUSION In patients with RA receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day. Clinicians should balance the benefits of low-dose glucocorticoids with this potential risk. PRIMARY FUNDING SOURCE National Institute of Arthritis and Musculoskeletal and Skin Diseases.

ObjectivesTo determine if plasma microbial small RNAs (sRNAs) are altered in patients with rheumatoid arthritis (RA) compared with control subjects, associated with RA disease-related features, and altered by disease-modifying antirheumatic drugs (DMARDs).MethodssRNA sequencing was performed on plasma from 165 patients with RA and 90 matched controls and a separate cohort of 70 patients with RA before and after starting a DMARD. Genome alignments for RA-associated bacteria, representative bacterial and fungal human microbiome genomes and environmental bacteria were performed. Microbial genome counts and individual sRNAs were compared across groups and correlated with disease features. False discovery rate was set at 0.05.ResultsGenome counts of Lactobacillus salivarius, Anaerobaculum hydrogeniformans, Staphylococcus epidermidis, Staphylococcus aureus, Paenisporosarcina spp, Facklamia hominis, Sphingobacterium spiritivorum, Lentibacillus amyloliquefaciens, Geobacillus spp, and Pseudomonas fluorescens were significantly decreased in the plasma of RA compared with control subjects. Three microbial transfer RNA-derived sRNAs were increased in RA versus controls and inversely associated with disease activity. Higher total microbial sRNA reads were associated with lower disease activity in RA. Baseline total microbial sRNAs were threefold higher among patients who improved with DMARD versus those who did not but did not change significantly after 6 months of treatment.ConclusionPlasma microbial sRNA composition is altered in RA versus control subjects and associated with some measures of RA disease activity. DMARD treatment does not alter microbial sRNA abundance or composition, but increased abundance of microbial sRNAs at baseline was associated with disease activity improvement at 6 months.

The ‘real-world’ patient population of metastatic melanoma is not fully represented in clinical trials investigating checkpoint inhibitors. We described therapy discontinuation in an unselected population-based cohort of adults with metastatic melanoma who started therapy with pembrolizumab, nivolumab, or nivolumab/ipilimumab from January 2015 to August 2017. Therapy discontinuation was defined as a gap between doses beyond 120 days, and/or initiation of another cancer therapy. We estimated drug-specific rate ratios for therapy discontinuation adjusted for age, sex, comorbidities, health care use, and past cancer therapies. We included 876 metastatic melanoma patients initiating pembrolizumab (44.3%), nivolumab/ipilimumab (31.2%), and nivolumab (24.5%). At 12 months of follow-up, the probabilities of therapy discontinuation were 49.9% (95% confidence interval, CI 43.6–56.5) for pembrolizumab, 58.8% (95% CI 50.5–67.3) for nivolumab, and 59.2% (95% CI 51.7–66.8) for nivolumab/ipilimumab. Stratified analyses based on prior cancer therapy, brain metastases at baseline, and sex showed similar trends. In multivariable analyses, compared with pembrolizumab, patients starting nivolumab (rate ratio 1.38, 95% CI 1.08–1.77) or nivolumab/ipilimumab (rate ratio 1.30, 95% CI 1.02–1.65) were more likely to discontinue therapy. Our findings indicate frequent discontinuations of checkpoint inhibitors at one year. The lower discontinuation associated with pembrolizumab should be confirmed in further studies.

The risk of coronavirus disease 2019 (COVID-19) and disease progression among patients using immunomodulatory therapy is unclear. Accordingly, we implemented an active surveillance project with USA/Canada Infectious Disease specialists via the Emerging Infections Network (EIN) to identify COVID-19 cases occurring in patients who use immunomodulatory therapy and to describe their clinical outcomes. EIN listserv members include 2396 infectious disease physicians in the USA/Canada linked via a moderated listserv. On 8 April via listserv, we requested reports of COVID-19 cases among patients receiving immunomodulatory therapy. Two weekly reminders were later sent and case reports were collected until 22 May. We collected information regarding patient demographics, COVID-19 test results, symptoms, hospitalisation details, complications, treatment, pre-existing conditions, concomitant therapies, and patient outcomes. We conducted descriptive analyses of these patient factors and compared differences between survivors and non-survivors. We grouped immunosuppressive therapies by class (table 1). View this table: Table 1 COVID-19 outcomes among autoimmune patients receiving immunomodulatory therapy Thirty-eight physicians screened over 2500 COVID-19 cases from which 77 (3%) were identified using immunomodulatory drugs. Of these, 52% were female, median age of 60 years (range, 16–84) and 83.1% had autoimmune disease (rheumatoid arthritis (19, 24.7%), ulcerative colitis (5, 6.5%) and sarcoidosis (5, 6.5%) were most common). Comorbidities included hypertension (26, 33.8%), diabetes (19, 24.7%), underlying chronic kidney disease (11, 14.3%) and others. All patients had PCR-confirmed COVID-19. Symptoms included dyspnoea (70.1%), fever (68.8%) and cough (64.9%). At time of COVID-19 diagnosis, 31 (40%) were using biologic therapies including anti tumor necrosis factor (anti-TNF) therapies (n=16), rituximab (n=6), abatacept (n=2), tocilizumab (n=2) and other (n=5). Among those using non-biologics at baseline (46, 60%), the following therapies were in use: janus kinase (JAK) inhibitors (3, 6.5%), non-biologic disease-modifying antirheumatic drugs (DMARDs) (11, 24%), prednisone alone (5, 11%) or other (27, 59%). Among …

Aim: Treatment switching and healthcare costs were compared among biologic-naive psoriasis patients initiating apremilast or biologics with ≥12 months pre-/post-index continuous enrollment in Optum Clinformatics™ Data Mart. Methods: After propensity score matching, switch rates (new therapy post-index) and days between index and switch were assessed. Total and per-patient per-month costs by service type were assessed. Results: Apremilast initiators (n = 533) were matched and compared with biologic initiators (n = 955). Twelve-month cumulative switch rates and days to switch were similar. Apremilast initiators had significantly lower total healthcare costs than biologic initiators; apremilast switchers and nonswitchers had significantly lower per-patient per-month costs than biologic switchers and nonswitchers, driven mainly by reduced outpatient pharmacy costs. Conclusion: Apremilast initiators had lower healthcare costs even with treatment switching.

OBJECTIVE To identify and prioritize patient- and rheumatologist-perceived barriers to achieving disease control. METHODS Patients with rheumatoid arthritis (RA) and rheumatologists from the Corrona registry were invited by e-mail to participate in nominal groups. Two separate lists of barriers were created, 1 from RA patient-only nominal groups and the other from rheumatologist-only nominal groups, and barriers were sorted into themes. Next, using an online survey, a random sample of RA patients from the Corrona registry were asked to rank their top 3 barriers to achieving disease control. RESULTS Four nominal groups totaling 37 RA patients identified patient barriers to achieving control of RA activity that were classified into 17 themes. Three nominal groups totaling 25 rheumatologists identified barriers that were classified into 11 themes. The financial aspects of RA care ranked first for both types of nominal groups, while medication risk aversion ranked second among the perceived barriers of the physician nominal group and third among those of the RA patient nominal group. Among the 450 RA patients surveyed, 77% considered RA a top health priority, and 51% reported being aware of the treat-to-target strategy for RA care; the 3 most important patient-perceived challenges to achieving disease control were RA prognosis uncertainty, medication risk aversion, and the financial/administrative burden associated with RA care. CONCLUSION There are common, potentially modifiable, patient- and rheumatologist-reported barriers to achieving RA disease control, including perceived medication risk aversion, suboptimal treatment adherence, and suboptimal patient-physician communication regarding the benefits of tight control of disease activity in RA. Addressing these obstacles may improve adherence to goal-directed RA care.

Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to estimate the overall incidence of safety events in patients with UC in a real-life population cohort for comparison with the tofacitinib UC clinical trial program. Methods Clinical trial-like criteria were applied to an IBM MarketScan® claims database population-based cohort (n = 22,967) of patients with UC (October 2010 to September 2015) to identify a UC trial-like cohort treated with tumor necrosis factor inhibitors (TNFi; n = 6366) to compare with the tofacitinib UC clinical trial cohort (n = 1157). Results Incidence rates (events per 100 patient-years; [95% confidence interval]) in the UC trial-like cohort were as follows: serious infections, 3.33 (2.73–4.02); opportunistic infections (OIs; excluding herpes zoster [HZ]), 1.45 (1.06–1.93); HZ, 1.77 (1.34–2.29); malignancies (excluding nonmelanoma skin cancer [NMSC]), 0.63 (0.43–0.90); NMSC, 1.69 (1.35–2.10); major adverse cardiovascular events (MACE), 0.51 (0.31–0.79); pulmonary embolism (PE), 0.54 (0.30–0.89); deep vein thrombosis (DVT), 1.41 (1.00–1.93); and gastrointestinal perforations, 0.31 (0.16–0.54). Compared with the UC trial-like cohort, tofacitinib-treated patients had numerically lower incidence rates for serious infections (1.75 [1.27–2.36]), OIs (excluding HZ; 0.16 [0.04–0.42]), NMSC (0.78 [0.47–1.22]), PE (0.16 [0.04–0.41]), and DVT (0.04 [0.00–0.23]), and a higher rate for HZ (3.57 [2.84–4.43]); rates for malignancies (excluding NMSC), MACE, and gastrointestinal perforations were similar. Conclusions When acknowledging limitations of comparing claims data with controlled clinical trial data, incidence rates for HZ among TNFi-treated patients in the UC trial-like cohort were lower than in the tofacitinib UC clinical trial cohort; rates for serious infections, OIs, NMSC, PE, and DVT were numerically higher. ClinicalTrials.gov NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612.

Objectives To examine healthcare resource utilization (HRU) and costs in a population of managed care enrollees who experienced an osteoporotic fracture. Study design Retrospective cohort study using the Optum Research Database (January 2007 to May 2017). Methods All-cause and osteoporosis-related HRU and costs were analyzed in patients 50 years and older with a qualifying index fracture and continuous enrollment with medical and pharmacy benefits for 12 months preindex (baseline period). Results Of 1,841,263 patients with fractures during the identification period, 302,772 met eligibility criteria. Two-thirds (66.6%) were 65 years and older, 71.6% were women, and 41.2% were commercial (not Medicare Advantage) enrollees. The most common fracture sites were spine (21.9%), radius/ulna (19.5%), and hip (13.7%). Mean (SD) total all-cause healthcare cost was $34,855 ($56,094), with most paid by health plans ($31,863 [$55,025]) versus patients ($2992 [$2935]). Most healthcare costs were for medical ($31,766 [$54,943]) versus pharmacy ($3089 [$6799]) services. Approximately 75% of patients received rehabilitation services (mean [SD] cost = $18,025 [$41,318]). Diagnosis of index fracture during an inpatient stay versus an outpatient visit (cost ratio, 2.16; 95% CI, 2.13-2.19) and fractures at multiple sites (cost ratio, 1.23; 95% CI, 1.21-1.26) were the leading predictors of cost. Kaplan-Meier estimated cumulative second-fracture rates were 6.6% at 1 year, 12.3% at 2 years, 16.9% at 3 years, and 20.9% at 4 years after index fracture. Conclusions These findings suggest a significant economic burden associated with fractures, including a high total all-cause cost of care. Early identification and treatment of patients at high risk of fractures are of paramount importance to reduce fracture risk and associated healthcare costs.

Background Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody tests are often measured at the time of rheumatoid arthritis (RA) diagnosis but may not be repeated and therefore not available in electronic health record (EHR) data; lab test results are unavailable in most administrative claims databases. ICD10 coding allows discrimination between rheumatoid factor positive (M05) (“seropositive”) and seronegative (M06) patients, but the validity of these codes has not been examined. Methods Using the ACR’s Rheumatology Informatics System for Effectiveness (RISE) EHR-based registry and U.S. MarketScan data where some patients have lab test results, we assembled two cohorts. Seropositive RA was defined having a M05 diagnosis code on the second rheumatologist encounter, M06 similarly identified seronegative RA, and RF and anti-CCP lab test results were the gold standard. We calculated sensitivity (Se) and positive predicted value (PPV) of the M05/M06 diagnosis codes. Results We identified 43,581 eligible RA patients (RISE) and 1185 (MarketScan) with RF or anti-CCP lab test results available. Using M05 as the proxy for seropositive RA, sensitivity = 0.76, PPV = 0.82 in RISE, and Se = 0.73, PPV = 0.84 in MarketScan. Results for M06 as a proxy for seronegative RA were comparable in RISE, albeit somewhat lower in MarketScan. Over 3 consecutive visits, approximately 90% of RA patients were coded consistently using either M05 or M06 at each visit. Conclusion Under ICD10, M05 and M06 diagnosis codes are reasonable proxies to identify seropositive and seronegative RA with high sensitivity and positive predictive values if lab test results are not available.

Background Little is known about PRO measures patients find most important for disease, treatment effectiveness/health outcomes. In this study, we examined PROs selected by patients with rheumatologic conditions to further elucidate which disease symptoms they found most important to track within ArthritisPower registry. As the study is ongoing, we discuss initial PRO selections of study participants. Methods Adult US patients with self-reported rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), osteoporosis (OP), osteoarthritis (OA), fibromyalgia syndrome (FMS) in ArthritisPower were invited to participate and prompted to select up to ten PRO (symptom) measures they felt were important to track their condition at baseline via ArthritisPower smartphone and Web-based app. PROs Measurement Information System (PROMIS) instruments focusing on symptoms of pain, physical and cognitive function, mental health, fatigue, social function, work impact, sexual function, and sleep, and Outcomes Measures in Rheumatology (OMERACT) RA flare instrument (only for those with RA) and Lilly-developed morning joint-stiffness duration question were offered. At Month (m)1, m2, m3, participants were given the option to continue tracking their selected PRO measures or change. At m3, participants complete an exit survey prioritizing all measures selected during participation and specifying other symptoms not available they would have wanted to track. Descriptive statistics were conducted on baseline data. Results As of May 2019, 292 participants enrolled (251 completed baseline assessments). Mean age was 55.6 (9.2) years, 89.6% female, 91.2% White, mean disease duration of 12 (10.7) years; similar to the overall ArthritisPower population. Majority (64.1%) self-reported OA, followed by RA (49.0%), FMS (40.6%), PsA (26.3%), OP (20.3%), AS (15.5%), SLE (5.6%), not mutually exclusive. Top 3 PRO domains chosen at baseline were fatigue, mental health, pain (Table 1). Average number of instruments selected for baseline completion was 6.9 (2.4). Conclusion Participants prioritised tracking fatigue, aspects of mental health, pain, physical function, social function, sleep, morning stiffness. These findings provide insights into symptoms rheumatology patients find most important; useful to inform the design of future patient-centric clinical trials and real-world evidence generation. Disclosures T. Daud (Non-Author Presenter) None. W.B. Nowell: Shareholder/stock ownership; WN has Ownership Interest (stocks, stock options, or other ownership interest excluding diversified mutual funds). C.L. Kannowski Corporate appointments; CLK is an employee of Eli Lilly and Company. Shareholder/stock ownership; CLK owns stock options at Eli Lilly and Company. K. Gavigan: None. Z. Cai: Corporate appointments; ZC is an employee of Eli Lilly and Company. Shareholder/stock ownership; shareholder of Eli Lilly and Company. A. Cardoso: Corporate appointments; AC is an employee of Eli Lilly and Company. Shareholder/stock ownership; AC is a stockholder of Eli Lilly and Company. T. Hunter: Corporate appointments; TH is an employee of Eli Lilly and Company. Shareholder/stock ownership; TH is a shareholder of Eli Lilly and Company. J. Birt: Corporate appointments; JB is an employee of Eli Lilly and Company. Shareholder/stock ownership; JB is a shareholder of Eli Lilly and Company. J. Workman: Corporate appointments; JW is an employee of Eli Lilly and Company. J. Curtis: Consultancies; JC has received Consulting Fees from AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, UCB. Grants/research support; JC has received grants/research support from AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, UCB.

ObjectivesThe impact of immunosuppression on postoperative outcomes has primarily been studied in patients undergoing joint replacement surgery. We aimed to evaluate the impact of biologics and glucocorticoids on outcomes after other major surgeries.MethodsThis retrospective cohort study used Medicare data 2006–2015 to identified adults with rheumatoid arthritis undergoing hip fracture repair, abdominopelvic surgery (cholecystectomy, hysterectomy, hernia, appendectomy, colectomy) or cardiac surgery (coronary artery bypass graft, mitral/aortic valve). Logistic regression with propensity-score-based inverse probability weighting compared 90-day mortality and 30-day readmission in patients receiving methotrexate (without a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD)), a tumour necrosis factor inhibitor (TNFi) or a non-TNFi biologic/tsDMARD ResultsWe identified 10 777 eligible surgeries: 3585 hip fracture, 5025 abdominopelvic and 2167 cardiac surgeries. Compared with patients receiving methotrexate, there was no increase in the risk of 90-day mortality or 30-day readmission among patients receiving a TNFi (mortality adjusted OR (aOR) 0.83 (0.67 to 1.02), readmission aOR 0.86 (0.75 to 0.993)) or non-TNFi biologic/tsDMARD (mortality aOR 0.78 (0.49 to 1.22), readmission aOR 1.02 (0.78 to 1.33)). Analyses stratified by surgery category were similar. Risk of mortality and readmission was higher with 5–10 mg/day of glucocorticoids (mortality aOR 1.41 (1.08 to 1.82), readmission aOR 1.26 (1.05 to 1.52)) or >10 mg/day (mortality aOR 1.64 (1.02 to 2.64), readmission aOR 1.60 (1.15 to 2.24)) versus no glucocorticoids, although results varied when stratifying by surgery category.ConclusionsRecent biologic or tsDMARD use was not associated with a greater risk of mortality or readmission after hip fracture, abdominopelvic or cardiac surgery compared with methotrexate. Higher dose glucocorticoids were associated with greater risk.

Purpose: In contrast to randomized clinical trials, comparative safety and effectiveness assessments of osteoporosis medications in clinical practice may be subject to confounding by indication. We used negative control outcomes to detect residual confounding when comparing osteoporosis medications. Methods: Using MarketScan Commercial and Supplemental claims, we identified women aged ≥55 years who initiated an oral bisphosphonate (BP) (risedronate, alendronate, or ibandronate), denosumab (an injected biologic), or intravenous zoledronic acid (ZA) from October 1, 2010 to September 30, 2015. Women with Paget's disease or cancer were excluded. We compared individual oral BPs to each other, denosumab to ZA, denosumab to oral BPs, and ZA to oral BPs, with respect to 11 negative control outcomes identified by subject matter experts. We estimated the 12-month cumulative risk difference (RD) using inverse probability of treatment and censoring weights. Results: Among 148 587 women, most initiated alendronate (57%), followed by ibandronate (12%), ZA (11%), risedronate (10%), and denosumab (10%). Compared with denosumab, patients initiating ZA had similar risks of all negative control outcomes. Compared with oral BPs, patients initiating denosumab had a higher risk of a wellness visit (RD = 1.2%, 95% CI: 0.4, 1.9) and a lower risk of receiving herpes zoster vaccine (RD = −0.6%, 95% CI: −1.1, −0.2). Comparing ZA with oral BP initiators resulted in two outcomes with positive associations. Conclusions: Caution is warranted when comparing injectable vs oral osteoporosis medications, given the potential for unmeasured confounding. Evaluating negative control outcomes could be a standard validity check prior to conducting comparative studies.

We sought to characterized patterns of aPL testing in a large general population sample from the United States. Using Truven Health MarketScan laboratory data from 2010–2015 we identified individuals tested for lupus anticoagulant(LA), anti-cardiolipin (aCL), and anti-beta2-glycoprotein1(aGP1). Our research was approved by the McGill institutional review board (A04-M47-12B). We identified 33,456 individuals with at least one aPL test. Among these, only 6,391 (19%) had all three tests (LA, aCL, aGP1) performed. Confirmatory aPL testing was performed at least 12 weeks later in 77%, 45%, and 41% of initially positive LA, aCL, and aGP1, respectively. Of those re-tested after ≥12 weeks, only 255 (10.6%) were found to have a confirmatory positive aPL test. These findings highlight that aPL testing may often be incompletely performed. Further investigations will be required to better understand the low rate of a confirmatory positive aPL test ≥12 weeks after the initial test.

BACKGROUND: Discontinuation of bisphosphonates (BP) or a “drug holiday” after several years of treatment is increasingly common. However, the association of drug holiday duration with future fracture risk is unclear. OBJECTIVES: We evaluated the rate of fracture in relation to various lengths of drug holidays among women receiving long-term BP therapy. RESEARCH DESIGN: Observational cohort study using US Medicare data 2006–2016. Incidence rates (IRs) and Cox proportional hazards models were used to evaluate the rate and adjusted hazard ratios (aHRs) controlling for potential confounders. SUBJECTS: Women aged 65 years and above enrolled in fee-for-service Medicare who had been adherent (≥ 80%) to alendronate, risedronate, or zoledronate for ≥ 3 years. MEASURES: Hip, humerus, distal forearm, and clinical vertebral fracture. RESULTS: Among 81,427 eligible women observed for a median (interquartile range) of 4.0 (2.5, 5.3) years, 28% of women underwent a drug holiday. In the alendronate cohort (73% overall), the IR of hip fracture among women who discontinued BP for > 2 years was 13.2 per 1000 person-years. Risk was increased (aHR =1.3, 1.1–1.4) versus continuing therapy (IR =8.8, referent). Rates were elevated for humerus fracture with discontinuation >2 years (aHR =1.3, 1.1–1.66) and for clinical vertebral fracture with discontinuation > 2 years (aHR =1.2, 1.1–1.4). Results were similar for risedronate, zoledronate, and ibandronate for hip and clinical vertebral fracture. CONCLUSION: Discontinuing alendronate beyond 2 years was associated with increased risk of hip, humerus, and clinical vertebral fractures.

We investigated the factors associated with readiness for initiating osteoporosis treatment in women at high risk of fracture. We found that women in the contemplative stage were more likely to report previously being told having osteoporosis or osteopenia, acknowledge concern about osteoporosis, and disclose prior osteoporosis treatment. Understanding factors associated with reaching the contemplative stage of readiness to initiate osteoporosis treatment may inform the design of behavioral interventions to improve osteoporosis treatment uptake in women at high risk for fracture. We measured readiness to initiate osteoporosis treatment using a modified form of the Weinstein Precaution Adoption Process Model (PAPM) among 2684 women at high risk of fracture from the Activating Patients at Risk for OsteoPOroSis (APROPOS) clinical trial. Pre-contemplative participants were those who self-classified in the unaware and unengaged stages of PAPM (stages 1 and 2). Contemplative participants were those in the undecided, decided not to act, or decided to act stages of PAPM (stages 3, 4, and 5). Using multivariable logistic regression, we evaluated participant characteristics associated with levels of readiness to initiate osteoporosis treatment. Overall, 24% (N = 412) self-classified in the contemplative stage of readiness to initiate osteoporosis treatment. After adjusting for age, race, education, health literacy, and major osteoporotic fracture in the past 12 months, contemplative women were more likely to report previously being told they had osteoporosis or osteopenia (adjusted odds ratio [aOR] (95% CI) 11.8 (7.8–17.9) and 3.8 (2.5–5.6), respectively), acknowledge concern about osteoporosis (aOR 3.5 (2.5–4.9)), and disclose prior osteoporosis treatment (aOR 4.5 (3.3–6.3)) than women who self-classified as pre-contemplative. For women at high risk for future fractures, ensuring women’s recognition of their diagnosis of osteoporosis/osteopenia and addressing their concerns about osteoporosis are critical components to consider when attempting to influence stage of behavior transitions in osteoporosis treatment.

Objective.The clinical utility of the multibiomarker disease activity (MBDA) test for rheumatoid arthritis (RA) management in routine care in the United States has not been thoroughly studied.Methods.Using 2011–2015 Medicare data, we linked each patient with RA to their MBDA test result. Initiation of a biologic or Janus kinase (JAK) inhibitor in the 6 months following MBDA testing was described. Multivariable adjustment evaluated the likelihood of adding or switching biologic/JAK inhibitor, controlling for potential confounders. For patients with high MBDA scores who added a new RA therapy and were subsequently retested, lack of improvement in the MBDA score was evaluated as a predictor of future RA medication failure, defined by the necessity to change RA medications again.Results.Among 60,596 RA patients with MBDA testing, the proportion adding or switching biologics/JAK inhibitor among those not already taking a biologic/JAK inhibitor was 9.0% (low MBDA), 11.8% (moderate MBDA), and 19.7% (high MBDA, p < 0.0001). Similarly, among those already taking biologics/JAK inhibitor, the proportions were 5.2%, 8.3%, and 13.5% (p < 0.0001). After multivariable adjustment, referent to those with low disease MBDA scores, the likelihood of switching was 1.51-fold greater (95% CI 1.35–1.69) for patients with moderate MBDA scores, and 2.62 (2.26–3.05) for patients with high MBDA scores. Among those with high MBDA scores who subsequently added a biologic/JAK inhibitor and were retested, lack of improvement in the MBDA score category was associated with likelihood of future RA treatment failure (OR 1.61, 95% CI 1.27–2.03).Conclusion.The MBDA score was associated with both biologic and JAK inhibitor medication addition/switching and subsequent treatment outcomes.

Summary Among 377,561 female Medicare beneficiaries who sustained a fracture, 10% had another fracture within 1 year, 18% within 2 years, and 31% within 5 years. Timely management to reduce risk of subsequent fracture is warranted following all nontraumatic fractures, including nonhip nonvertebral fractures, in older women. Introduction Prior fracture is a strong predictor of subsequent fracture; however, postfracture treatment rates are low. Quantifying imminent (12–24 month) risk of subsequent fracture in older women may clarify the need for early postfracture management. Methods This retrospective cohort study used Medicare administrative claims data. Women ≥ 65 years who sustained a clinical fracture (clinical vertebral and nonvertebral fracture; index date) and were continuously enrolled for 1-year pre-index and ≥ 1-year (≥ 2 or ≥ 5 years for outcomes at those time points) post-index were included. Cumulative incidence of subsequent fracture was calculated from 30 days post-index to 1, 2, and 5 years post-index. For appendicular fractures, only those requiring hospitalization or surgical repair were counted. Death was considered a competing risk. Results Among 377,561 women (210,621 and 10,969 for 2- and 5-year outcomes), cumulative risk of subsequent fracture was 10%, 18%, and 31% at 1, 2, and 5 years post-index, respectively. Among women age 65–74 years with initial clinical vertebral, hip, pelvis, femur, or clavicle fractures and all women ≥ 75 years regardless of initial fracture site (except ankle and tibia/fibula), 7–14% fractured again within 1 year depending on initial fracture site; risk rose to 15–26% within 2 years and 28–42% within 5 years. Risk of subsequent hip fracture exceeded 3% within 5 years in all women studied, except those

To examine the importance of recent fracture as a predictor of imminent fracture risk, review the importance of prior fracture type and timing, and identify risk factors for recurrent osteoporotic fracture. Prior fracture type and timing impact risk of subsequent fracture that is largely independent of bone mineral density. Site of re-fracture is similar to original major osteoporotic fracture. Incidence of recurrent major osteoporotic fracture is greatest within the first year. Other risk factors include those that pertain to individual characteristics. Approved osteoporosis therapies reduce risk of recurrent fracture. Prior fracture timing, type, and individual characteristics are important components of predicting the risk of future fracture. Initiation of osteoporosis medication therapy should be started after initial fracture to reduce the risk of future fracture, though these medications typically take 6–12 months to have an effect, during which time is the highest rate of imminent re-fracture.

Background Patient-Powered Research Networks (PPRNs) are a unique type of patient-powered patient registry for patient-centered outcomes research requiring that stakeholder engagement play a key role in governance (eg, research guidance and decision making). The purpose of this report is to describe the governance structure of a newly formed PPRN and the activities undertaken prelaunch and postlaunch to evaluate and improve the engagement of patient stakeholders in governance. Methods During the 18-month start-up period of ArthritisPower, a PPRN for adult rheumatologic conditions, 12 members of the patient body of the PPRN governance completed a 12-item preassessment and postassessment based on the Patient-Centered Outcomes Research Institute (PCORI) Engagement Rubric. The assessment was intended to measure Patient Governor (PG) perceptions of their engagement in governance within the first 3 months of their involvement at an in-person orientation. Six months later, the PG Chair initiated a mid-year evaluation with the same group to identify areas for improvement. Semistructured phone interviews were conducted with 11 PGs who were asked to rate and explain their perceptions about their participation in PPRN governance, the progress of the PPRN toward conducting research, the support they receive from staff, and the support they receive from other PGs. Results were compiled and interpreted by the Chair with help from the coprincipal investigator. Results Preassessment/postassessments indicated that PGs understood their governance role and decision-making authority after in-person orientation and felt that major PPRN decisions were being made with their input. Feedback and scores from the PG-led mid-year evaluation coalesced around 3 themes: a preference for receiving news and updates via email to allow more discussion and decision making during conference calls, a desire for guidance about how best to help advance the PPRN toward the conduct of research, and a need to communicate with each other as a group outside of monthly conference calls. Suggested activities to support patient engagement in PPRN governance include communicating clear expectations, providing well-prepared tools for engagement, and conducting regular assessments. Conclusions Members of an online patient community are willing to share their expertise to participate in and shape research governance and bring both their professional and lived health experience to the development and improvement of PPRN governance structure. A patient-initiated and patient-led evaluation of governance communication procedures within the PPRN provided more specific recommendations for improvement than did an investigator-led preevaluation/postevaluation based on the PCORI Engagement Rubric.

OBJECTIVE Identifying incident rheumatoid arthritis (RA) is desirable in order to create inception cohorts. We evaluated an approach to identify incident RA in health plan claims data. METHODS Both Medicare and commercial claims data were linked to Corrona, a US RA registry. We evaluated the accuracy of year of RA onset in the registry (gold standard) versus different claims algorithms, varying International Classification of Diseases, Ninth Revision codes for RA/arthritis, duration of health plan enrollment preceding diagnosis (minimum of 1 versus 2 years), and use of RA medications. Results were reported as positive predictive values (PPVs) of the claims-based algorithm for incident RA. RESULTS Depending on the algorithm tested and whether patients were enrolled in Medicare or the commercial health plan, the PPVs for incident RA ranged from 68-81%. A 2-year clean period free of all RA-related diagnoses and medications was somewhat more optimal although, by comparison, a 1-year clean period yielded similar PPVs and retained approximately 90% more RA patients for analysis. CONCLUSION Claims-based algorithms can accurately identify incident RA.

The Multi-Biomarker Disease Activity (MBDA) score is a validated rheumatoid arthritis (RA) disease activity measure based on 12 serum biomarkers. Here, we evaluate short-term biological variability of MBDA scores to determine the magnitude of change that might be considered clinically meaningful. Twenty-eight adult seropositive RA patients with clinically stable disease and no changes in RA medications for 4 weeks prior to study were enrolled. Nine serum samples were obtained over four consecutive days (non-fasting). MBDA score variation was assessed day-to-day (daily) and within 24 h (diurnal). The standard deviation (SD) of MBDA scores was calculated by a linear mixed model including random effects for patient, day, and time of day. The minimally important difference (MID) was calculated as [Formula: see text]. A subgroup analysis was performed for patients with active RA (moderate or high MBDA score). The SD of MBDA score change in the full cohort was 4.7 in a combined daily-diurnal variation analysis, which corresponds with an MID of 11. The SD of MBDA score change in the subset of patients with active RA (moderate/high MBDA scores) was 3.6. This corresponds with an MID of 8 units in patients with active RA for whom clinicians are most likely to need guidance with respect to therapeutic decisions. Changes in MBDA score ≥ 8 represent a change in RA disease activity that clinicians can use as a benchmark for therapeutic drug efficacy and can be incorporated into a treat-to-target strategy.