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The article critiques a study on the effectiveness of herpes zoster vaccination in patients with diabetes mellitus, pointing out limitations such as the use of electronic health records for vaccination status estimation, lack of individual follow-up data, and potential biases in study design. The study's results are questioned due to database issues, missing information, methodological problems, demographic imbalances, and inconsistencies with existing evidence, suggesting that the estimates may not accurately reflect the true association. The authors recommend evaluating dataset limitations for specific analyses and using claims datasets or combined electronic health records/claims data for more accurate vaccine efficacy estimates. [Extracted from the article]

Objective: The objective of this study was to ascertain pegloticase persistence and adverse events associated with concomitant immunomodulatory drug treatment in patients with gout. Methods: We conducted a retrospective analysis of patients with gout using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness registry from January 2016 through June 2020. The first pegloticase infusion defined the index date. Based on concomitant immunomodulatory drug treatment, we identified three exposure groups: (1) immunomodulatory drug initiators (patients initiating an immunomodulatory prescription ±60 days from the index date), (2) prevalent immunomodulatory drug recipients (patients receiving their first immunomodulatory drug prescription >60 days before the index date with at least one prescription within ±60 days of the index date), and (3) immunomodulatory nonrecipients (patients receiving pegloticase without concomitant immunomodulatory drugs). We calculated the proportion of patients who achieved serum urate levels ≤6 mg/dL and who had laboratory abnormalities (white blood cell count <3.4 x 109/L, platelet count <135,000, hematocrit level <30%, alanine aminotransferase or aspartate aminotransferase level ≥1.5 times the upper limit normal value) within 180 days after the index date. Cox regression analyzed time to pegloticase discontinuation, controlling for potential confounders. Results: We identified 700 pegloticase recipients (91 immunomodulatory drug initiators, 33 prevalent immunomodulatory drug recipients, and 576 nonrecipients), with a median follow‐up of 14 months. Immunomodulatory drug recipients were less likely to discontinue pegloticase. The adjusted hazard ratios of pegloticase discontinuation associated with concomitant immunomodulatory drug initiation and prevalent treatment were 0.52 (95% confidence interval [CI] 0.37–0.75) and 0.69 (95% CI 0.42–1.16), respectively. Laboratory abnormalities were uncommon (<5%) and were not higher in concomitant immunomodulatory drug treatment. Conclusion: Consistent with clinical trials, results from this large observational registry suggest that concomitant immunomodulatory drug treatment improves pegloticase persistence. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to update a method to identify comorbid conditions using only medication information in circumstances in which diagnosis codes may be undercaptured, such as in single‐specialty electronic health records (EHRs), and to compare the distribution of comorbidities across Rx‐Risk versus other traditional comorbidity indices. Methods: Using First Databank, RxNorm, and its web‐based clients, RxNav and RxClass, we mapped Drug Concept Unique Identifiers (RxCUIs), National Drug Codes (NDCs), and Anatomical Therapeutic Chemical (ATC) codes to Rx‐Risk, a medication‐focused comorbidity index. In established rheumatoid arthritis (RA) and osteoarthritis (OA) cohorts within the Rheumatology Informatics System for Effectiveness registry, we then compared Rx‐Risk with other comorbidity indices, including the Charlson Comorbidity Index, Rheumatic Disease Comorbidity Index (RDCI), and Elixhauser. Results: We identified 965 unique ingredient RxCUIs representing the 46 Rx‐Risk comorbidity categories. After excluding dosage form and ingredient related RxCUIs, 80,911 unique associated RxCUIs were mapped to the index. Additionally, 187,024 unique NDCs and 354 ATC codes were obtained and mapped to the index categories. When compared to traditional comorbidity indices in the RA cohort, the median score for Rx‐Risk (median 6.00 [25th percentile 2, 75th percentile 9]) was much greater than for Charlson (median 0 [25th percentile 0, 75th percentile 0]), RDCI (median 0 [25th percentile 0, 75th percentile 0]), and Elixhauser (median 1 [25th percentile 1, 75th percentile 1]). Analyses of the OA cohort yielded similar results. For patients with a Charlson score of 0 (85% of total), both the RDCI and Elixhauser were close to 1, but the Rx‐Risk score ranged from 0 to 16 or more. Conclusion: The misclassification and under‐ascertainment of comorbidities in single‐specialty EHRs can largely be overcome by using a medication‐focused comorbidity index. [ABSTRACT FROM AUTHOR]

Purpose: Inpatient mortality is an important variable in epidemiology studies using claims data. In 2016, MarketScan data began obscuring specific hospital discharge status types for patient privacy, including inpatient deaths, by setting the values to missing. We used a machine learning approach to correctly identify hospitalizations that resulted in inpatient death using data prior to 2016. Methods: All hospitalizations from 2011 to 2015 with discharge status of missing, died, or one of the other subsequently obscured values were identified and divided into a training set and two test sets. Predictor variables included age, sex, elapsed time from hospital discharge until last observed claim and until healthcare plan disenrollment, and absence of any discharge diagnoses. Four machine learning methods were used to train statistical models and assess sensitivity and positive predictive value (PPV) for inpatient mortality. Results: Overall 1 307 917 hospitalizations were included. All four machine learning approaches performed well in all datasets. Random forest performed best with 88% PPV and 93% sensitivity for the training set and both test sets. The two factors with the highest relative importance for identifying inpatient mortality were having no observed claims for the patient on days 2–91 following hospital discharge and patient disenrollment from the healthcare plan within 60 days following hospital discharge. Conclusion: We successfully developed machine learning algorithms to identify inpatient mortality. This approach can be applied to obscured data to accurately identify inpatient mortality among hospitalizations with missing discharge status. [ABSTRACT FROM AUTHOR]

Objectives: 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. Methods: Using patients with RA in the CorEvitas registry with Medicare coverage in 2006–2019, we identified eligible patients who had at least 1 visit with moderate disease activity based on the Clinical Disease Activity Index (CDAI; CDAI >10 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, and 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 (MSMs). Results: A total of 3,254 patients with RA 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 with being in remission, the hazard ratio of hospitalized infection associated with low disease activity was 1.60 (95% confidence interval [95% CI] 1.13–2.28) and with moderate disease activity was 1.83 (95% CI 1.30–2.64). Conclusion: The risk of hospitalized infection was higher for patients with RA in low or moderate disease activity than for those in remission after accounting for the interplay of disease activity, RA treatments, treatment switching, and other potential confounders. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trial findings may not be generalizable to routine practice. This study evaluated sarilumab effectiveness in patients with rheumatoid arthritis (RA) and tested the real-world applicability of a response prediction rule, derived from trial data using machine learning (based on C-reactive protein [CRP] > 12.3 mg/l and seropositivity [anticyclic citrullinated peptide antibodies, ACPA +]). Methods: Sarilumab initiators from the ACR-RISE Registry, with ≥ 1 prescription on/after its FDA approval (2017–2020), were divided into three cohorts based on progressively restrictive criteria: Cohort A (had active disease), Cohort B (met eligibility criteria of a phase 3 trial in RA patients with inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi]), and Cohort C (characteristics matched to the phase 3 trial baseline). Mean changes in Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were evaluated at 6 and 12 months. In a separate cohort, predictive rule was tested based on CRP levels and seropositive status (ACPA and/or rheumatoid factor); patients were categorized into rule-positive (seropositive with CRP > 12.3 mg/l) and rule-negative groups to compare the odds of achieving CDAI low disease activity (LDA)/remission and minimal clinically important difference (MCID) over 24 weeks. Results: Among sarilumab initiators (N = 2949), treatment effectiveness was noted across cohorts, with greater improvement noted for Cohort C at 6 and 12 months. Among the predictive rule cohort (N = 205), rule-positive (vs. rule-negative) patients were more likely to reach LDA (odds ratio: 1.5 [0.7, 3.2]) and MCID (1.1 [0.5, 2.4]). Sensitivity analyses (CRP > 5 mg/l) showed better response to sarilumab in rule-positive patients. Conclusions: In real-world setting, sarilumab demonstrated treatment effectiveness, with greater improvements in the most selective population, mirroring phase 3 TNFi-refractory and rule-positive RA patients. Seropositivity appeared a stronger driver for treatment response than CRP, although optimization of the rule in routine practice requires further data. Plain Language Summary: Rheumatoid arthritis (RA) is a condition that may cause joint damage, if untreated. Sarilumab is an advanced medication, approved for treating moderate-to-severe RA in patients not responding to initial standard medicines. Clinical trials have shown that sarilumab improves RA symptoms; however, some people do not respond. This is a common problem in RA treatment. Physicians measure proteins in people's blood (called biomarkers; e.g., anticyclic citrullinated peptide antibodies [ACPA], C-reactive protein [CRP], and rheumatoid factor [RF]) to predict a medicine's response. A previous study showed that people with positive blood tests for ACPA and CRP (> 12.3 mg/l) responded well to sarilumab; this study was based on machine learning (a branch of science using computers) and identified factors that could be linked to treatment benefits. The present study analyzed routine data of 2949 people from the ACR-RISE Registry and showed an improvement in RA symptoms after 6 and 12 months of sarilumab, with a greater improvement noted in patients previously treated with other medicines. Biomarkers were tested in 205 people to check whether they could predict treatment response in day-to-day life. People were called rule-positive if they tested positive for RF and/or ACPA with CRP > 12.3 mg/l, and otherwise rule-negative. After 24 weeks of treatment, rule-positive people had a greater chance of disease improvement than rule-negative people. These results showed the benefits of sarilumab in RA in routine care and suggested the usefulness of machine learning in identifying biomarkers that physicians can use to make treatment decisions. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to evaluate the factors associated with regional variation of rheumatoid arthritis (RA) disease burden in the US. Methods: In a retrospective cohort analysis of Rheumatology Informatics System for Effectiveness (RISE) registry data, seropositivity, RA disease activity (Clinical Disease Activity Index [CDAI], Routine Assessment of Patient Index Data–version 3 [RAPID3]), socioeconomic status (SES), geographic region, health insurance type, and comorbidity burden were recorded. An Area Deprivation Index score of more than 80 defined low SES. Median travel distance to practice sites' zip codes was calculated. Linear regression was used to analyze associations between RA disease activity and comorbidity adjusting for age, sex, geographic region, race, and insurance type. Results: Enrollment data for 184,722 patients with RA from 182 RISE sites were analyzed. Disease activity was higher in African American patients, in those from Southern regions, and in those with Medicaid or Medicare coverage. Greater comorbidity was prevalent in patients in the South and those with Medicare or Medicaid coverage. There was moderate correlation between comorbidity and disease activity (Pearson coefficient: RAPID3 0.28, CDAI 0.15). High‐deprivation areas were mainly in the South. Less than 10% of all participating practices cared for more than 50% of all Medicaid recipients. Patients living more than 200 miles away from specialist care were located mainly in Southern and Western regions. Conclusion: A disproportionately large portion of socially deprived, high comorbidity, and Medicaid‐covered patients with RA were cared for by a minority of rheumatology practices. Studies are needed in high‐deprivation areas to establish more equitable distribution of specialty care for patients with RA. [ABSTRACT FROM AUTHOR]

Objective: To determine whether multimorbidity is associated with treatment changes and achieving target disease activity thresholds in patients with active rheumatoid arthritis (RA). Methods: 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. Results: 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]). Conclusion: 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. [ABSTRACT FROM AUTHOR]

As the scientific research community along with healthcare professionals and decision makers around the world fight tirelessly against the coronavirus disease 2019 (COVID‐19) pandemic, the need for comparative effectiveness research (CER) on preventive and therapeutic interventions for COVID‐19 is immense. Randomized controlled trials markedly under‐represent the frail and complex patients seen in routine care, and they do not typically have data on long‐term treatment effects. The increasing availability of electronic health records (EHRs) for clinical research offers the opportunity to generate timely real‐world evidence reflective of routine care for optimal management of COVID‐19. However, there are many potential threats to the validity of CER based on EHR data that are not originally generated for research purposes. To ensure unbiased and robust results, we need high‐quality healthcare databases, rigorous study designs, and proper implementation of appropriate statistical methods. We aimed to describe opportunities and challenges in EHR‐based CER for COVID‐19‐related questions and to introduce best practices in pharmacoepidemiology to minimize potential biases. We structured our discussion into the following topics: (1) study population identification based on exposure status; (2) ascertainment of outcomes; (3) common biases and potential solutions; and (iv) data operational challenges specific to COVID‐19 CER using EHRs. We provide structured guidance for the proper conduct and appraisal of drug and vaccine effectiveness and safety research using EHR data for the pandemic. This paper is endorsed by the International Society for Pharmacoepidemiology (ISPE). [ABSTRACT FROM AUTHOR]

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 < 0.0001) and 0.7 units (P = 0.135), respectively; among those with (n = 51) and without (n = 72) baseline fatigue, mean increase in PROMIS fatigue was 3.9 units (P = 0.0003) and 0.4 units (P = 0.554), respectively. Conclusions: Digital remote patient monitoring presents an opportunity to detect and address medication tolerability in real time. Using a novel study design to control for between-person confounding, the magnitude of nausea and fatigue experienced by participants with RA and PsA temporally related to weekly MTX use was substantial. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We estimated meaningful change thresholds (MCTs) for Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue and Pain Interference in rheumatoid arthritis (RA).Methods: The 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."Results: Baseline 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.Conclusion: The 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this study authors aimed to investigate the barriers to participation of a sample of Jamaican women in mammography screening. The data were obtained from a previous survey that was conducted in Jamaica from June to August 2013 in the four parishes (Hanover, St. James, Trelawny, and Westmoreland) served by the Western Regional Health Authority (WRHA). WRHA served four hospitals, five non-randomized health centers, and five sites of community events. The sample consisted of women ranging in age between 35 and 83 years, with the mean age of 50.2 (SD = 10.6). The authors used a logistic regression to determine the extent to which variables were associated with breast cancer screening. The level of significace was 0.1 for the bivariate and multivariable analysis. The main factors associated with the lack of breast cancer screening among the women were: being less than 50 years old, single, never thought about breast cancer screening, in need of childcare, and having more than three children. We identified significant barriers to participation in mammography screening experienced by a sample of Jamaican women. Our results suggest that it is necessary to increase the awareness of the importance of breast screening importance among the women who may never have thought about mammography. [ABSTRACT FROM AUTHOR]

Purpose To assess the capture of biologics (originator and biosimilar) in the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) Distributed Research Network (DRN), with a focus on medical claim National Drug Code (NDC), a new data field, and Healthcare Common Procedure Coding System (HCPCS) modifier. Methods: We conducted a repeated cross‐sectional study among patients with medical and pharmacy benefits enrolled in insurance plans participating in the BBCIC DRN between 1 January 2013 and 30 September 2017. We calculated the proportion of medical claims with ≥1 NDC and identified select biologics using four different approaches: (a) specific HCPCS alone, (b) specific HCPCS and NDC, (c) non‐specific HCPCS with NDC, and (d) HCPCS with modifiers (applicable to biosimilars). Numbers of dispensings were calculated for each biologic by approach and select patient and claim characteristics. Results: More than 1.5 million eligible participants contributed approximately 4 million person‐years of data, including 1.2 billion medical claims. The proportion of medical claims with ≥1 NDC increased from 1.2% in 2013 to 3.0% in 2017. Medical claim NDCs identified 39% and 28% of vedolizumab dispensed in 2014 and 2015 and 30% of Epogen/Procrit dispensed overall. Out of 26,381 filgrastim biosimilar dispensings identified, 51% had a HCPCS modifier and 12% had a medical claim NDC for Zarxio. HCPCS modifiers and medical claim NDCs were present for 38% and 3% of all infliximab biosimilars dispensed (total n = 1,244). Conclusions: Medical claim NDC and HCPCS modifier improves identification of select biologics without product‐specific HCPCS code, thereby facilitating product‐specific biologic research. [ABSTRACT FROM AUTHOR]

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA).Objective: Our objective was to compare the incidence rates (IRs) of adverse events in tofacitinib clinical trials and real-world observational data for alternative treatments.Methods: The tofacitinib "dose-comparison cohort" included months 0-12 of two phase III studies (tofacitinib 5 [n = 238] and 10 [n = 236] mg twice daily [BID]); the "all-tofacitinib comparison cohort" (n = 783) included two phase III and one ongoing long-term extension study (data cutoff May 2016). An "observational comparison cohort" (n = 5799) comprised patients initiating a conventional synthetic disease-modifying antirheumatic drug (DMARD), biologic DMARD, or apremilast in the US Truven MarketScan database from 2010 to 2015. IRs for serious infections (SIEs; requiring hospitalization), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, and major adverse cardiovascular events (MACE) across cohorts were qualitatively compared.Results: IRs (patients with events/100 patient-years) for SIEs were similar between the tofacitinib dose-comparison cohort (5 mg BID: 1.3; 10 mg BID: 2.0) and the observational comparison cohort (1.1-7.9; treatment dependent). The tofacitinib dose-comparison cohort had a higher rate of HZ (5 mg BID: 2.0; 10 mg BID: 2.7) than did the observational comparison cohort (0.8-2.0). IRs for NMSC were generally lower in the all-tofacitinib comparison cohort (0.5) than in the observational comparison cohort (0.4-6.0). IRs for MACE, malignancies excluding NMSC, and NMSC were similar between cohorts.Conclusion: In patients with PsA, tofacitinib had a safety profile similar to that of other systemic therapies in real-world settings, except for the risk of HZ, a known risk of tofacitinib.Trial Registration: ClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364. [ABSTRACT FROM AUTHOR]

Objective: Health information technology has enabled efficient measurement of patient-reported outcomes (PROs). The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) is becoming more widely adopted for research and routine care, and some PROMIS instruments might be substituted for lengthier, legacy PRO instruments.Methods: Four PROMIS computer-adaptive testing (CAT) instruments (pain interference, physical function, sleep disturbance, and fatigue) and the Routine Assessment of Patient Index Data 3 (RAPID3), along with pain intensity and patient global assessment score, were administered to participants in the ArthritisPower registry. The RAPID3 was predicted using different combinations of these variables to create a new score (CAT-PROMIS RAPID3). Kappa statistics and Bland-Altman 95% limits of agreement were used to measure agreement between the observed versus predicted RAPID3.Results: A total of 6,154 eligible patients contributed 11,275 observations. The mean ± SD age was 52.7 ± 10.5 years, and 93% of patients were women. The median assessment times ranged from 29 seconds (PROMIS sleep disturbance) to 116 seconds (RAPID3). As single pairwise comparisons, the PROMIS CATs examined were modestly correlated (r approximately 0.4-0.7) to one other and RAPID3. Together with the pain intensity and patient global assessment, the PROMIS instruments explained a high fraction of total variance (R2 = 0.97) of the RAPID3 score. In the model with the highest agreement (κ = 0.93) between the observed RAPID3 and the CAT-PROMIS predicted RAPID3, Bland-Altman 95% limits of agreement showed minimal residual differences and no systematic biases.Conclusion: There was excellent agreement between the observed RAPID3 and predicted RAPID3 scores estimated using several PROMIS instruments. The Multidimensional Health Assessment Questionnaire and patient global assessment components of RAPID3 may be unnecessary if PROMIS scores are available. [ABSTRACT FROM AUTHOR]

Marginal structural models incorporate not only current disease activity and GC dose, but also previous disease activity and other treatments. While Dr. Boers raises concerns that patients taking GCs may have "hidden" disease activity, incorporating previous disease activity and treatments should help address this concern. We thank Dr. Boers for his interest and comments ([1]) on our recently published study evaluating the association between disease activity and hospitalized infection among patients with RA in the CorEvitas registry ([2]). [Extracted from the article]

Objectives. To determine rates of human papillomavirus (HPV) vaccine adherence to the 2011 and 2016 Advisory Committee for Immunization Practices (ACIP) recommendations in the United States. Methods. We conducted a retrospective cohort study by using the 2011 to 2017 Marketscan data for beneficiaries aged 9 to 26 years who had at least 1 claim for HPV vaccination between January 1, 2011, and January 1, 2017. According to the 2011 ACIP recommendation, adherence is defined as 30 to 90 days between the first and second vaccination and 168 to 212 days between the first and third vaccination. According to the 2016 recommendation, preadolescents are classified as adherent if they had 2 claims of vaccination within 168 to 212 days. We calculated proportions of completion and adherence by recommendation. Results. Among patients classified under the 2011 ACIP recommendation (n = 2 164 096), 8.3% completed all 3 doses of the vaccine series. Of those who completed, 69.6% were considered adherent to the recommended schedule. Completion and adherence increased to 9.6% and 70.8%, respectively, among patients who were classified under the 2016 ACIP recommendation. Conclusions. Simpler recommendations lead to better adherence to the HPV vaccination schedule. [ABSTRACT FROM AUTHOR]

Adverse events related to long‐term use of bisphosphonates have raised interest in temporary drug discontinuation. Trends in bisphosphonate discontinuation and restart, as well factors associated with these decisions, are not fully understood at a population level. We investigated temporal trends of bisphosphonate discontinuation from 2010 to 2015 and identified factors associated with discontinuation and restart of osteoporosis therapy. Our cohort consisted of long‐term bisphosphonate users identified from 2010 to 2015 Medicare data. We defined discontinuation as ≥12 months without bisphosphonate prescription claims. We used conditional logistic regression to compare factors associated with alendronate discontinuation or osteoporosis therapy restart in the 120‐day period preceding discontinuation or restart referent to the 120‐day preceding control periods. Among 73,800 long‐term bisphosphonate users, 59,251 (80.3%) used alendronate, 6806 (9.2%) risedronate, and 7743 (10.5%) zoledronic acid, exclusively. Overall, 26,281 (35.6%) discontinued bisphosphonates for at least 12 months. Discontinuation of bisphosphonates increased from 1.7% in 2010, reaching a peak of 14% in 2012 with levels plateauing through 2015. The factors most strongly associated with discontinuation of alendronate were: benzodiazepine prescription (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [CI] 2.1, 3.0), having a dual‐energy X‐ray absorptiometry (DXA) scan (aOR = 1.8; 95% CI 1.7, 2.0), and skilled nursing facility care utilization (aOR = 1.8; 95% CI 1.6, 2.1). The factors most strongly associated with restart of osteoporosis therapy were: having a DXA scan (aOR = 9.9; 95% CI 7.7, 12.6), sustaining a fragility fracture (aOR = 2.8; 95% CI 1.8, 4.5), and an osteoporosis or osteopenia diagnosis (aOR = 2.5; 95% CI 2.0, 3.1). Our national evaluation of bisphosphonate discontinuation showed that an increasing proportion of patients on long‐term bisphosphonate therapy discontinue medications. The factors associated with discontinuation of alendronate were primarily related to worsening of overall health status, whereas traditional factors associated with worsening bone health were associated with restarting osteoporosis medication. © 2019 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Objective: Despite strong recommendations for routine measurement of rheumatoid arthritis (RA) disease activity and associated treatment changes to attain remission/low disease activity, the measurement tools that clinicians use to evaluate RA patients' disease activity and frequency of treatment change have not been well characterized. Therefore, we evaluated different measurement tools that physicians used to assess RA disease activity and associated RA treatment changes.Methods: Using data from the Rheumatology Informatics System for Effectiveness (RISE) registry from January 2016 through June 2017, and using the following criteria: age ≥18 years, diagnosis of RA (International Classification of Diseases, Ninth and Tenth Revision, codes), ≥2 RISE visits, and ≥1 RA disease activity measure scored in 2016, we classified eligible patients' drug use at the index visit as monotherapy or combination therapy with conventional synthetic (cs) and biologic disease-modifying antirheumatic drugs (bDMARDs). Outcomes include change in treatment over 12 months. Mixed models identified factors associated with treatment change.Results: Among 50,996 eligible patients, 27,274 had longitudinal data. The most commonly used measures were RAPID3 (78.9%) and the Clinical Disease Activity Index (CDAI) (34.2%). The frequency of treatment change during follow-up was relatively low (35.6-54.6%), even for patients with moderate/high disease activity according to RAPID3 or CDAI scores. Older patients (age ≥75 years; adjusted odds ratio [ORadj ] 0.63 [95% confidence interval (95% CI) 0.50-0.78]) and those already receiving combination therapy with csDMARDs (ORadj 0.45 [95% CI 0.33-0.61]) or combination therapy with bDMARDs (ORadj 0.30 [95% CI 0.24-0.38]) were less likely to change RA treatment even after multivariable adjustment.Conclusion: Using the American College of Rheumatology's national RISE registry, one- to two-thirds of RA patients failed to change their treatment, even when experiencing moderate/high disease activity. Multimodal interventions directed at both patients and providers are needed to encourage shared decision-making, goal-directed care, and to overcome barriers to treatment escalation. [ABSTRACT FROM AUTHOR]

Objective: To determine the proportion of primary lipid screening among patients with rheumatoid arthritis (RA) and compare it with those among patients with diabetes mellitus (DM) and patients with neither RA nor DM, and to assess whether primary lipid screening varied according to the health care provider (rheumatologist versus non-rheumatologist).Methods: We analyzed claims data from US private and public health plans from 2006-2010. Eligibility requirements included continuous medical and pharmacy coverage for ≥12 months (baseline period) and >2 physician diagnoses and relevant medications to define RA, DM, RA and DM, or neither condition. Among the 330,695 eligible participants, we calculated the proportion with a lipid profile ordered during the 2 years following baseline. Time-varying Cox proportional hazard models were used to determine the probability of hyperlipidemia screening in participants with RA according to provider specialty.Results: More than half of the patients were ages 41-71 years. Among patients with RA (n = 12,182), DM (n = 62,834), RA and DM (n = 1,082), and those who did not have either condition (n = 167,811), the proportion screened for hyperlipidemia was 37%, 60%, 55%, and 41%, respectively. Patients with RA who visited a rheumatologist and a non-rheumatology clinician during follow-up had a 55% (95% confidence interval 1.36-1.78) higher screening probability than those who only visited a rheumatologist.Conclusion: Primary lipid screening was suboptimal among patients with RA. It was also lower for patients with DM and minimally different from the general population. Screening was higher for RA patients who received care from both a rheumatologist and a non-rheumatologist (e.g., primary care physician). [ABSTRACT FROM AUTHOR]

Objective: Increased incidence of herpes zoster (HZ) has been observed with JAK inhibitors such as tofacitinib. However, whether concomitant methotrexate (MTX) and/or glucocorticoids confer additional (additive or multiplicative) risk is unclear. We evaluated HZ risk in tofacitinib users with and without MTX and glucocorticoids.Methods: Within MarketScan and Medicare data (2011-2016), we identified all patients with rheumatologist-diagnosed rheumatoid arthritis initiating treatment with tofacitinib (index date); demographics and baseline covariates were evaluated in the year prior to the index date. HZ was ascertained using International Classification of Diseases, Ninth Revision or Tenth Revision codes with antiviral drug use (±7 days). Multivariable Cox regression was used to evaluate hazard ratios (HRs) for HZ in tofacitinib users with and without current concomitant MTX and glucocorticoids, controlling for baseline covariates.Results: We studied 8,030 new tofacitinib users (83.3% women). The mean ± SD age was 60.3 ± 12.6 years. HZ incidence in tofacitinib users was numerically lowest in the absence of glucocorticoids (3.4 per 100 patient-years with MTX; 3.7 per 100 patient-years without MTX). An approximately 2-fold increased incidence of HZ was observed for tofacitinib users receiving either glucocorticoids alone (6.0 per 100 patient-years) or both MTX plus glucocorticoids (6.5 per 100 patient-years). The adjusted HR for HZ in tofacitinib users was unchanged (HR 0.99 [95% confidence interval (95% CI) 0.64-1.54]) when given only with MTX, but was increased (HR 1.96 [95% CI 1.33-2.88]) for tofacitinib plus glucocorticoids. Older age and female sex were also risk factors, while prior vaccination was associated with a strong trend for lower risk.Conclusion: In tofacitinib users, HZ occurred at a rate of approximately 4% per year and was further doubled with glucocorticoid exposure. Concomitant MTX did not confer additional risk. Zoster vaccination may decrease risk. [ABSTRACT FROM AUTHOR]

Objective: Multiple studies have shown seemingly unfavorable changes in lipid profiles associated with interleukin-6 receptor (IL-6R) antagonists and some other therapies for rheumatoid arthritis. The aim of this study was to assess the real-world cardiovascular disease (CVD) risk associated with tocilizumab, the first anti-IL-6R medication approved for the treatment of RA.Methods: We conducted a cohort study using 2006-2015 Medicare and MarketScan claims for patients with RA in whom treatment with biologic disease-modifying antirheumatic drugs was initiated after January 1, 2010. The primary outcome was a composite of myocardial infarction, stroke, and fatal CVD, assessed using a validated method. The influence of potential confounding due to RA disease activity was assessed in a subgroup analysis (~5-10% of biologic therapy initiations) using the multi-biomarker disease activity (MBDA) score.Results: A total of 88,463 patients with RA were included. The crude incidence rate (IR) per 1,000 patient-years for composite CVD events among Medicare patients ranged from 11.8 (95% confidence interval [95% CI] 9.7-14.4) for etanercept users to 17.3 (95% CI 15.2-19.7) for infliximab users. The crude IR for pooled users of a tumor necrosis factor inhibitor was 15.0 (95% CI 13.9-16.3). Compared to tocilizumab, the corresponding adjusted hazard ratios (HRs) were 1.01 (95% CI 0.79-1.28) for abatacept, 1.16 (95% CI 0.89-1.53) for rituximab, 1.10 (95% CI 0.80-1.51) for etanercept, 1.33 (95% CI 0.99-1.80) for adalimumab, and 1.61 (95% CI 1.22-2.12) for infliximab. There were no statistically significant differences in the risk of CVD between tocilizumab and any other biologic when MarketScan data were used. Results were robust in numerous subgroup analyses and after external adjustment to control for RA disease activity in the subgroup of patients with linked MBDA test results (n = 4,156).Conclusion: Tocilizumab was associated with a CVD risk comparable to that for etanercept as well as a number of other biologics used for the treatment of RA. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Real-World Sarilumab Use and Rule Testing to Predict Treatment Response in Patients with Rheumatoid Arthritis: Findings from the RISE Registry" published in the journal Rheumatology & Therapy. The original article contained four incorrect supplementary files, which have now been replaced with the correct file. The authors of the article are Jeffrey R. Curtis, Huifeng Yun, Lang Chen, Stephanie S. Ford, Hubert van Hoogstraten, Stefano Fiore, Kerri Ford, Amy Praestgaard, Markus Rehberg, and Ernest Choy. The correction has been made to ensure the accuracy of the information presented in the article. [Extracted from the article]

Objective: To identify the perspectives of patients with rheumatoid arthritis (RA) on electronic recording of between-visit disease activity and other patient-reported outcomes (PROs) and on sharing this information with health care providers or peers.Methods: Patients with RA were recruited to participate in focus groups from December 2014 to April 2015. The topic guide and analysis were based on the Andersen-Newman framework. Sessions were audiorecorded, transcribed, independently coded, and analyzed for themes.Results: Thirty-one patients participated in 7 focus groups. Their mean ± SD age was 51 ± 13.1 years, 94% were women, 52% were African American, 11% were Hispanic, and 37% were white. Three themes emerged: provider communication, information-seeking about RA, and social and peer support. Participants expressed a willingness to track disease activity data to share with health care providers electronically if providers would act on the information. Participants envisioned symptom tracking and information sharing as a mechanism to relay and obtain reliable information about RA. Participants were also interested in electronic communication between visits if it facilitated learning about symptom management and enhanced opportunities for social support among patients with RA.Conclusion: Patients with RA may be amenable to electronic collection and sharing of PRO-type data between clinical encounters if it facilitates communication with health care providers and provides access to reliable information about RA. Providing patients with social support was important for enhancing PROs collection by helping them overcome barriers by using electronic devices and overcome reservations about the value of these data. [ABSTRACT FROM AUTHOR]

Objective: The 2013 American College of Cardiology/American Heart Association cholesterol treatment guidelines recommend statins for patients with diabetes mellitus ages 40-75 years due to their elevated cardiovascular disease (CVD) risk. We compared the incidence of hospitalized acute myocardial infarction (MI), stroke, and coronary revascularization according to whether patients had diabetes mellitus, rheumatoid arthritis (RA), both, or neither.Methods: Using 2006-2010 private and public health plan claims, we identified 4 mutually exclusive retrospective cohorts ages >40 years: patients with RA and diabetes mellitus, RA only, diabetes mellitus only, or neither condition. Patients with prevalent CVD were excluded. Outcomes included acute MI and stroke, identified from inpatient discharge diagnosis codes, and coronary revascularization from procedure codes. Across the 4 cohorts, we calculated incidence rates (IRs) of the outcomes, standardized to the 2010 US census age and sex distribution.Results: We identified 920,772 eligible participants. The age- and sex-standardized IRs (per 1,000 person-years) for MI were highest among patients with RA and diabetes mellitus (IR 12.6 [95% confidence interval (95% CI) 10.7-14.7]), followed by patients with diabetes mellitus only (IR 10.7 [95% CI 10.3-11.0]), RA only (IR 5.7 [95% CI 5.2-6.3]), and with neither condition (IR 4.2 [95% CI 4.1-4.3]).Conclusion: Findings from the present study suggest that while CVD risk in RA is elevated, it is lower in magnitude compared to the CVD risk associated with diabetes mellitus. Therefore, considering RA a diabetes mellitus risk-equivalent with respect to hyperlipidemia management may not be appropriate. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) disease activity and associated systemic inflammation has been associated with serious infection (SIEs), myocardial infarction (MI) and coronary heart disease (CHD) events based on a few registry studies or clinical trials. There are few data from large-scale population-based studies given feasibility challenges in conducting such investigations.Methods: Multibiomarker disease activity (MBDA) test scores (n=77 641) were linked to Medicare for US patients with RA. Outcomes of interest were hospitalised pneumonia/sepsis (SIE), MI and a composite CHD outcome. The MBDA score ranges from 1 to 100 and was analysed as time-varying. Cox proportional hazards models evaluated the association between MBDA score and SIEs, MI and CHD events, controlling for potential confounders. A sensitivity analysis excluded C reactive protein (CRP) from the MBDA score.Results: There were 17 433 and 16 796 patients eligible for the SIE and MI/CHD analyses, respectively. Mean (SD) age was 69 (11) years, 79% were women, 81% were white and 38% were disabled. Over 16 424 person-years of follow-up, there were 452 SIE events, 132 MIs and 181 CHD events. Higher MBDA scores were associated with SIEs (HR=1.32, 95% CI 1.23 to 1.41 per 10 unit MBDA score change). For MI/CHD events, a threshold effect was present; higher disease activity by MBDA score was associated with increased MI (HR=1.52, 95% CI 0.92 to 2.49) and CHD rates (HR=1.54, 95% CI 1.01 to 2.34, comparing scores ≥30 vs <30). Analyses of the MBDA score without CRP yielded similar results.Conclusion: Higher MBDA scores were associated with hospitalised infection, MI and CHD events in a large, predominantly older, US RA population. [ABSTRACT FROM AUTHOR]

Objective: The optimal timing of tumor necrosis factor antagonists before elective surgery is unknown. This study evaluated the association between infliximab timing and serious infection after elective hip or knee arthroplasty.Methods: A retrospective cohort study evaluated US Medicare patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months of elective knee or hip arthroplasty from 2007 to 2013. Propensity-adjusted analyses examined whether infliximab stop timing (time between the most recent infusion and surgery) was associated with hospitalized infection within 30 days or prosthetic joint infection (PJI) within 1 year.Results: Hospitalized infection within 30 days occurred after 270 of 4,288 surgeries (6.3%). Infliximab stop timing <4 weeks versus 8-12 weeks was not associated with an increase in infection within 30 days (propensity-adjusted odds ratio [OR] 0.90 [95% confidence interval (95% CI) 0.60-1.34]). The rate of PJI was 2.9 per 100 person-years and was not increased in patients with stop timing <4 weeks versus 8-12 weeks (hazard ratio [HR] 0.98 [95% CI 0.52-1.87]). Glucocorticoid dosage >10 mg/day was associated with increased risk of 30-day infection (OR 2.11 [95% CI 1.30-3.40]) and PJI (HR 2.70 [95% CI 1.30-5.60]). Other risk factors for infection included elderly age, comorbidities, revision surgery, and previous hospitalized infection.Conclusion: Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short- or long-term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially >10 mg/day, was associated with an increased infection risk. [ABSTRACT FROM AUTHOR]

Background: Hypersensitivity reactions (HSRs) can occur with any of the available biologic agents used to treat rheumatoid arthritis (RA). We compared drug-specific risks for HSRs among RA patients enrolled in the US Medicare program.Methods: Using Medicare data, we identified new users of infused infliximab, abatacept, rituximab, tocilizumab, golimumab, and injected biologic agents. After identifying HSRs using validated algorithms, for each biologic agent, we calculated the cumulative incidence over 6 months and the incidence rates (IRs) in 0-1, 2-14, and 15-30 days of administration. For each biologic agent administration, followup started on the infusion/injection date and ended at HSR, subsequent biologic agent administration, death, coverage loss, 30-day followup, or December 31, 2013, whichever occurred first. Adjusted robust Poisson regression was used to compare the HSR risks across biologic agents. A sensitivity analysis was conducted using a nested case-crossover design.Results: We identified 725,591 biologic agent administrations and 248 HSRs among 80,587 new users of biologic agents. Of these, 26.9% occurred in users of intravenous abatacept, 4.6% in rituximab, 5.8% in intravenous tocilizumab, 22.9% in infliximab, and 39.7% in injectable anti-tumor necrosis factor inhibitors (anti-TNFi). The cumulative incidence of HSRs over 6 months for all biologic agents was low (<1%).The IRs for HSRs ranged from 2.4 (abatacept) to 239.5 (rituximab) per 106 person-days. After adjustment, and using injectable anti-TNFi over 0-30 days as the referent, rituximab, infliximab, abatacept, and tocilizumab infusions were associated with a statistically significant higher risk of HSR. The sensitivity analysis yielded similar results.Conclusion: Among RA patients taking biologic agents, rituximab and infliximab were most strongly associated with HSRs. The absolute IRs of HSR events for all biologic agent exposures were low. [ABSTRACT FROM AUTHOR]

Objective Opioid prescribing recently has come under intense scrutiny. However, longitudinal patterns of prescription opioid receipt in a population-based cohort of patients with chronic pain, such as those with rheumatoid arthritis (RA), have not been well characterized. The aim of this study was to examine both trends over time and variability in individual physician prescribing of short-term and long-term use of opioids. Methods We identified a cohort of RA patients based on 2006-2014 Medicare data and evaluated longitudinal time trends in 'regular' use of opioids. A separate analysis conducted in 2014 assessed rheumatologist-specific variability in regular use of opioid prescriptions in patients with RA. Results We identified 97,859 RA patients meeting the eligibility criteria. The mean age of the patients was 67 years, 80% were female, 82% were white, and 12% were African American. The most commonly used opioids were those that combined acetaminophen with hydrocodone or propoxyphene. Regular opioid prescribing increased slowly but peaked in 2010 before propoxyphene was withdrawn from the market. Following the withdrawal of propoxyphene, receipt of hydrocodone and tramadol increased commensurately, and overall opioid use declined only slightly. Factors associated with regular use of opioids included younger age, female sex, African American race, back pain, fibromyalgia, anxiety, and depression. Variability between US rheumatologists (n = 4,024) in prescribing the regular use of opioids for their RA patients was high; in the average rheumatologist's practice, 40% of RA patients used prescription opioids regularly. In almost half of the patients, at least some opioid prescriptions were written by a rheumatologist, and 14% received opioids that were co-prescribed concurrently by more than 1 physician. Conclusion In the US, opioid use in older patients with RA peaked in 2010 and is now declining slightly. Withdrawal of propoxyphene from the US market in 2010 had minimal effect on overall opioid use, because use of propoxyphene was replaced by increased use of other opioids. [ABSTRACT FROM AUTHOR]

Introduction Treat to target guidelines recommend achieving remission or low disease activity in rheumatoid arthritis (RA). However, the reduction in adverse events and costs associated with lower disease activity is unclear. Methods We used Corrona linked to Medicare data to identify RA patients. Time varying disease activity was measured using Clinical Disease Activity Index (CDAI); outcomes included all-cause hospitalization, a composite of hospitalization or emergency department (ED) visits, mortality, and medical costs. Outcome-specific Cox proportional models evaluated the adjusted hazard ratios between disease activity and outcomes, controlling for potential confounders including comorbidities grouped into four patient phenotypes. Costs were analyzed with mixed models using a Gaussian distribution with log transformation. Results Depending on outcome, 4593 RA patients contributed up to 12 001 person years. Median age was 71 years, 75% women. At baseline, approximately 50-60% of patients were in remission or low disease activity. There was a dose-response relationship between RA disease activity (remission, low, moderate, and high) and the incidence of hospitalizations (13.1, 17.8, 21.2, 27.5 per 100 py, respectively); all adjusted hazard ratios were significant: 0.68 (remission), 0.87 (low), and 1.24 (high) compared with moderate disease activity. Similar trends were observed for ED visits and mortality. The crude difference in annual medical costs between remission ($11 145) and moderate disease activity ($17 646) was $−6 500; the adjusted difference (95%CI) was $−3133 (−4737.72, −1528.43). Conclusion Leveraging the benefits of linking registry and administrative data together, lower disease activity in RA was associated with incrementally reduced risks of all-cause hospitalization, ED visits, mortality, and medical costs in a dose-dependent fashion. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Herpes zoster (HZ) is an opportunistic infection caused by varicella-zoster virus and observed with increasing frequency in patients receiving immunosuppressive therapies. The literature has suggested that the risk of stroke may increase shortly after HZ, but little is known about this association in patients with autoimmune diseases, who are at increased risk of both zoster and stroke. Methods Medicare data from January 1, 2006 through December 31, 2013 were used to identify patients with autoimmune diseases. The outcome of interest was hospitalized stroke. The hypothesis tested was that the incidence of stroke immediately following HZ is increased compared to the incidence of stroke at later time points. Secondary analyses included assessment of the impact of antiviral therapy on subsequent stroke, as well as the influence of varicella-zoster virus-related complications on stroke incidence. Results The crude incidence of stroke ranged from a high of 2.30 per 100 patient-years (95% confidence interval [95% CI] 0.96-5.52) within 90 days of HZ in patients who had HZ-related cranial nerve complications and did not receive treatment to a low of 0.87 per 100 patient-years (95% CI 0.75-1.02) at 366-730 days in those without complication who received antiviral treatment. After multivariable adjustment for multiple stroke-related factors, the overall incidence rate ratio (IRR) for stroke in the first 90 days after HZ was 1.36 (95% CI 1.10-1.68) compared to stroke occurring at 366-730 days after HZ. The risk was greater for patients with zoster and cranial nerve complications (IRR 2.08 [95% CI 0.99-4.36]). Prompt antiviral therapy was associated with lower incidence of subsequent stroke (IRR 0.83 [95% CI 0.70-0.98]). Conclusion In patients with autoimmune diseases, incident HZ was associated with as much as a 2-fold increased risk of stroke in the subsequent few months. These data underscore the urgency of developing strategies for reducing the risk of varicella-zoster virus. [ABSTRACT FROM AUTHOR]

Objective To evaluate gastrointestinal (GI) perforation in rheumatoid arthritis (RA) patients receiving tofacitinib, tocilizumab, or other biologic agents. Methods Using health plan data from 2006 through 2014, RA patients without prior GI perforation were identified. Those in whom treatment with tofacitinib or a biologic agent was being initiated were followed up for incident GI perforation with hospitalization. Crude incidence rates were calculated by exposure. Adjusted Cox proportional hazards models were used to evaluate the association between GI perforation and exposures. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated. Results A cohort of 167,113 RA patients was analyzed. Among them, 4,755 began treatment with tofacitinib, 11,705 with tocilizumab, 115,047 with a tumor necrosis factor inhibitor (TNFi), 31,214 with abatacept, and 4,392 with rituximab. Compared to TNFi recipients, abatacept recipients were older, tofacitinib and rituximab recipients were younger, and tocilizumab recipients were similar in age. Patients beginning treatment with a non-TNFi agent were more likely to have previously received biologic agents than patients beginning treatment with a TNFi. The incidence of GI perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.55 (tocilizumab), 1.07 (abatacept), 0.73 (rituximab), and 0.83 (TNFi). Most perforations occurred in the lower GI tract: the incidence of lower GI tract perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.26 (tocilizumab), 0.76 (abatacept), 0.48 (rituximab), and 0.46 (TNFi). Lower GI tract perforation risk was significantly elevated with tocilizumab treatment, and numerically elevated with tofacitinib treatment, versus treatment with TNFi. Adjusted HRs were 2.51 (95% CI 1.31-4.80) for tocilizumab and 1.94 (95% CI 0.49-7.65) for tofacitinib. Older age (HR 1.16 per 5 years [95% CI 1.10-1.22]), diverticulitis/other GI conditions (HR 3.25 [95% CI 1.62-6.50]), and prednisone use at >7.5 mg/day (HR 2.29 [95% CI 1.39-3.78]) were associated with lower GI tract perforation. The incidence of upper GI tract perforation was similar among all drug exposures. Conclusion The risk of lower GI tract perforation associated with tocilizumab treatment, and possibly tofacitinib treatment, is elevated compared to that associated with TNF blockade. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risks of herpes zoster (HZ) and herpes simplex virus (HSV) infection associated with tofacitinib compared with biologic agents among patients with rheumatoid arthritis (RA).Methods: Using health plan data from 2010 to 2014, patients with RA initiating tofacitinib or biologics with no history of HZ or HSV were identified, as were incident cases of HZ or HSV. Crude incidence rates were calculated by drug exposure. Cox proportional hazards models evaluated the adjusted association between tofacitinib and HZ, and a composite outcome of HZ or HSV.Results: A total of 2526 patients initiating tofacitinib were compared with initiations of other biologics: anti-tumour necrosis factor (TNF) (n=42 850), abatacept (n=12 305), rituximab (n=5078) and tocilizumab (n=6967). Patients receiving tofacitinib were somewhat younger (mean age 55 years) versus those on other biologics, and somewhat less likely to use concomitant methotrexate (MTX) (39% vs 43%-56%, depending on drug). Crude incidence of HZ associated with tofacitinib was 3.87/100 patient-years (py). After multivariable adjustment, HZ risk was significantly elevated, HR 2.01 (95% CI 1.40 to 2.88) compared with abatacept. Rates and adjusted HRs for all other RA biologics were comparable with each other and abatacept. Older age, female sex, prednisone >7.5 mg/day, prior outpatient infection and greater number of hospitalisations were also associated with increased HZ risk. Incidence rates for the combined outcome were greatest for tofacitinib (7.61/100 py) and also significantly elevated after adjustment (HR=1.40, 95% CI 1.09 to 1.81).Conclusions: The rate of zoster associated with tofacitinib was approximately double that observed in patients using biologics. [ABSTRACT FROM AUTHOR]

Objectives: To compare the coronary heart disease risk among patients with rheumatoid arthritis (RA) initiating common biologic disease-modifying antirheumatic drugs of different mechanisms.Methods: We conducted a retrospective cohort study of patients with RA enrolled in Medicare, a public health plan covering >90% of US residents 65 years or older, from 2006 to 2012 who (1) initiated a biologic, (2) had complete medical and pharmacy coverage for at least 12 months before biologic initiation and (3) were free of coronary heart disease at the time of initiation. We compared the incidence rates (IRs) of (1) acute myocardial infarction (AMI) and (2) a composite outcome of AMI or coronary revascularisation and used multivariable adjusted Cox regression models to examine the associations between the type of biologic and the two outcomes.Results: We identified 47 193 eligible patients with RA with mean age 64 (SD 13) years; 85% were women. Crude IRs for AMI ranged from 5.7 to 8.8 cases per 1000 person-years (PYs). AMI risk was significantly elevated among antitumour necrosis factor (anti-TNF) initiators overall (adjusted HR (aHR) 1.3; 95% CI 1.0 to 1.6) and individually among etanercept (aHR 1.3; 95% CI 1.0 to 1.8) and infliximab (aHR 1.3; 95% CI 1.0 to 1.6) compared with abatacept initiators. Crude IRs for the composite outcome ranged from 7.6 to 14.5 per 1000 PYs. Tocilizumab initiators were at reduced risk of the composite outcome compared with abatacept initiators (aHR 0.64, 95% CI 0.41 to 0.99).Discussion: Findings from this observational study of patients with RA suggested that anti-TNF biologics may be associated with higher AMI risk compared with abatacept. [ABSTRACT FROM AUTHOR]

Objective Breast cancer recurrence may be promoted by immunosuppression due to decreased immune surveillance. The aim of this study was to examine the rates of breast cancer recurrence in patients with immune-mediated disease and treated breast cancer who received therapy with methotrexate, thiopurines, or anti-tumor necrosis factor (anti-TNF). Methods Three retrospective cohort studies within Medicare (2000-2012) included women with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) who underwent surgery for primary breast cancer. Recurrent or second primary breast cancers occurring more than 365 days after the initial surgery were identified. Separate Cox regression models were used to examine the risk of cancer recurrence in patients treated with methotrexate, thiopurines, or anti-TNF agents after surgery, each compared with no use. Analyses were matched for type of breast surgery and receipt and type of adjuvant therapy. Results Across all medication groups, 107 women experienced breast cancer recurrence during 5,196 person-years. The incidence rates were 20.3 and 19.6 per 1,000 person-years in methotrexate users and nonusers, respectively, 32.3 and 17.6 in thiopurine users and nonusers, respectively, and 22.3 and 19.5 in anti-TNF users and nonusers, respectively. There was no significantly increased risk of breast cancer recurrence with use of methotrexate (adjusted hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 0.67-1.69), anti-TNF therapy (HR 1.13, 95% CI 0.65-1.97), or thiopurines (HR 2.10, 95% CI 0.62-7.14). Conclusion The risk of breast cancer recurrence in patients who received methotrexate, thiopurine, or anti-TNF therapy was not statistically significantly increased, although we cannot rule out a 2-fold or greater increased risk in those treated with thiopurines. These data provide reassurance to clinicians choosing to start methotrexate or anti-TNF therapy in RA or IBD patients with treated breast cancer. [ABSTRACT FROM AUTHOR]