Changes in the Workforce Characteristics of Providers Who Care for Adult Patients With Rheumatologic and Musculoskeletal Disease in the United States.

OBJECTIVE: The aim of this study was to describe the adult rheumatology workforce in the United States, assess change in rheumatology providers over time, and identify variation in rheumatology practice characteristics. METHODS: Using national Medicare claims data from 2006 to 2020, clinically active rheumatology physicians and advanced practice providers (APPs) were identified. Each calendar year was used for inclusion, exclusion, and analysis, and providers were determined to be entering, exiting, or stable based upon presence or absence in the prior or subsequent years of data. Characteristics (age, gender, practice type, rural, and region) of rheumatologists were determined for 2019 and in mutually exclusive study periods from 2009 to 2011, 2012 to 2015, and 2016 to 2019. The location of rheumatology practice was determined by billing tax identification and mapped. Demographics of physicians exiting or entering the rheumatology workforce were compared separately to those stable by logistic regression. RESULTS: The clinically active adult rheumatology workforce identified in US Medicare in 2019 was 5,667 rheumatologists and 379 APPs. From 2009 to 2020, the number of rheumatologists increased 23% and the number of APPs increased 141%. There was an increase in female rheumatologists over time, rising to 43% in 2019. Women and those employed by a health care system were more likely to exit, and those in a small practice or in the South were less likely to exit. CONCLUSION: The overall number of clinically active rheumatology providers grew more than 20% over the last decade to a high of 6,036 in 2020, although this rate of growth appears to be flattening off in later years.

Assessment of Real-World Patient-Reported Outcomes in Patients Initiating Biologic Agents for the Treatment of Autoimmune Diseases: An Observational Study in Four Patient-Powered Research Networks.

Background: The most reliable and meaningful approach for inclusion of patient-reported outcomes (PROs) in the evaluation of real-world clinical effectiveness of biologics in the treatment of autoimmune diseases is u ncertain. This study aimed to assess and compare the proportions of patients who had abnormalities in PROs measuring important general health domains at the initiation of treatment with biologics, as well as the effects of baseline abnormalities on subsequent improvement. Methods: PROs were collected for patient participants with inflammatory arthritis, inflammatory bowel disease, and vasculitis using Patient-Reported Outcomes Measurement Information System instruments. Scores were reported as T-scores normalized to the general population in the United States. Baseline PROs scores were collected near the time of biologic initiation, and follow-up scores were collected 3 to 8 months later. In addition to summary statistics, the proportion of patients with PROs abnormalities (scores ≥5 units worse than the population norm) was determined. Baseline and follow-up scores were compared, and an improvement of ≥5 units was considered significant. Results: There was wide variation across autoimmune diseases in baseline PROs scores for all domains. For example, the proportion of participants with abnormal baseline pain interference scores ranged from 52% to 93%. When restricted to participants with baseline PROs abnormalities, the proportion of participants experiencing an improvement of ≥5 units was substantially higher. Conclusion: As expected, many patients experienced improvement in PROs following initiation of treatment with biologics for autoimmune diseases. Nevertheless, a substantial proportion of participants did not exhibit abnormalities in all PROs domains at baseline, and these participants appear less likely to experience improvement. For PROs to be reliably and meaningfully included in the evaluation of real-world medication effectiveness, more knowledge and careful consideration are needed to select the most appropriate patient populations and subgroups for inclusion and evaluation in studies measuring change in PROs.

Accuracy of administrative claims prescription fill data to estimate glucocorticoid use and dose in patients with rheumatoid arthritis.

PURPOSE: To assess accuracy of administrative claims prescription fill-based estimates of glucocorticoid use and dose, and approximate bias from glucocorticoid exposure misclassification. METHODS: We identified adults with rheumatoid arthritis with linked Medicare and CorEvitas registry data. An algorithm identifying glucocorticoid use and average dose over 90 days from Medicare prescription fills was compared to physician-reported measures from a CorEvitas visit during the same period, using weighted kappa to compare doses (none, ≤5 mg, 5-10 mg, >10 mg/day). A deterministic sensitivity analysis examined the effect of exposure misclassification on estimated glucocorticoid-associated infection risk from a prior study. RESULTS: We identified 621 observations among 494 patients. Prescription fills identified glucocorticoid use in 41.9% of observations versus 31.1% identified by CorEvitas physician-report. For glucocorticoid use (yes/no), prescription fills had sensitivity 88.1% (95% CI 82.7-92.3), specificity 79.0% (74.8-82.7), PPV 65.4% (59.3-71.2), NPV 93.6% (90.6-95.9), and 81.8% agreement with CorEvitas, with kappa 0.61 (moderate to substantial agreement). There was 89.5% agreement between prescription fills and physician-reported doses, with weighted kappa 0.56 (moderate agreement). Applying these results to a prior Medicare study evaluating glucocorticoid-associated infection risk [risk ratio 1.44 (95% CI 1.41-1.48)] led to an externally adjusted risk ratio of 1.74 when accounting for exposure misclassification, representing -17% bias in infection risk estimate. CONCLUSIONS: This study supports the use of claims data to estimate glucocorticoid use and dose, but investigators should account for exposure misclassification, which may lead to underestimates of glucocorticoid risks. Our results could be applied to adjust risk estimates in other studies that use prescription fills to estimate glucocorticoid use.

Clinical and Economic Burden of Herpes Zoster in Patients with Rheumatoid Arthritis: A Retrospective Cohort Study Using Administrative Claims.

OBJECTIVE: To estimate the incremental healthcare resource utilization (HRU) and cost burden posed by herpes zoster (HZ) in adult patients with rheumatoid arthritis (RA) in the United States. METHODS: A retrospective cohort study was conducted using an administrative claims database containing commercial and Medicare Advantage with Part D data, between October 2015 and February 2020. Patients with RA and HZ (RA+/HZ+) or RA without HZ (RA+/HZ-) were identified based on diagnosis codes and relevant medications. Outcomes measured included HRU and medical, pharmacy, and total costs at month 1, quarter 1, and year 1 after the index date (HZ diagnosis for RA+/HZ+ cohort, randomly assigned for RA+/HZ- cohort). Generalized linear models incorporating propensity scores and other covariates were used to estimate differences in outcomes between cohorts. RESULTS: A total of 1866 patients from the RA+/HZ+ cohort and 38,846 patients from the RA+/HZ- cohort were included. Hospitalizations and emergency department visits occurred more frequently in the RA+/HZ+ than the RA+/HZ- cohort, especially in the month after HZ diagnosis (adjusted incidence rate ratio [95% confidence interval (CI)] for hospitalizations: 3.4 [2.8; 4.2]; emergency department visits: 3.7 [3.0; 4.4]). Total costs were also higher in the month after HZ diagnosis (mean adjusted cost difference [95% CI]: $3404 [$2089; $4779]), with cost differences driven by increased medical costs ($2677 [$1692; $3670]). CONCLUSIONS: These findings highlight the high economic burden of HZ among individuals with RA in the United States. Strategies to reduce the risk of HZ in patients with RA (such as vaccination) may serve to reduce this burden. Video abstract.

Comparability of Osteoporosis Treatment Groups Among Female Medicare Beneficiaries in the United States.

It is often difficult to obtain valid estimates of comparative treatment effectiveness and safety owing to differences across patient populations taking different medications in the real world. One approach for assessing comparability between treatment groups in effectiveness studies is to use negative control outcomes (NCOs). NCOs share similar sources of bias with the primary outcomes but have no plausible causal relationship to the treatment of interest. Observing differences in the risk of NCOs thus provides evidence for residual confounding between groups. This retrospective study assessed the comparability of postmenopausal women, treated with osteoporosis medications with various mechanisms of action such as denosumab (receptor activator of nuclear factor κB ligand [RANKL] inhibitor), zoledronic acid (bisphosphonate derivative), or oral bisphosphonates including alendronate. Administrative claims data were extracted from the US Centers for Medicare and Medicaid Services' Chronic Condition Warehouse database (May 2010-December 2016). Propensity scores were used to match denosumab patients 1:1 to comparators. Four nonfracture NCOs and three early fracture NCOs (before substantial biologic effects of treatment would be expected) were assessed over 1-year and 3-month follow-up periods, respectively. According to comparability decision rules established a priori, patients initiating denosumab were comparable to those initiating zoledronic acid or alendronate, irrespective of prior osteoporosis treatment experience. Among new users, new switchers, and in the historical fracture subgroup, no meaningful differences were observed in the cumulative incidence of the seven NCOs comparing denosumab to zoledronic acid. This empirical examination can assist in the selection of appropriate comparator groups for future comparability research using real-world data. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Using pooled electronic health records data to conduct pharmacoepidemiology safety studies: Challenges and lessons learned.

PURPOSE: We assessed the suitability of pooled electronic health record (EHR) data from clinical research networks (CRNs) of the patient-centered outcomes research network to conduct studies of the association between tumor necrosis factor inhibitors (TNFi) and infections. METHODS: EHR data from patients with one of seven autoimmune diseases were obtained from three CRNs and pooled. Person-level linkage of CRN data and Centers for Medicare and Medicaid Services (CMS) fee-for-service claims data was performed where possible. Using filled prescriptions from CMS claims data as the gold standard, we assessed the misclassification of EHR-based new (incident) user definitions. Among new users of TNFi, we assessed subsequent rates of hospitalized infection in EHR and CMS data. RESULTS: The study included 45 483 new users of TNFi, of whom 1416 were successfully linked to their CMS claims. Overall, 44% of new EHR TNFi prescriptions were not associated with medication claims. Our most specific new user definition had a misclassification rate of 3.5%-16.4% for prevalent use, depending on the medication. Greater than 80% of CRN prescriptions had either zero refills or missing refill data. Compared to using EHR data alone, there was a 2- to 8-fold increase in hospitalized infection rates when CMS claims data were added to the analysis. CONCLUSIONS: EHR data substantially misclassified TNFi exposure and underestimated the incidence of hospitalized infections compared to claims data. EHR-based new user definitions were reasonably accurate. Overall, using CRN data for pharmacoepidemiology studies is challenging, especially for biologics, and would benefit from supplementation by other sources.

Incidence of Herpes Zoster in Patients With Rheumatoid Arthritis in the United States: A Retrospective Cohort Study.

OBJECTIVE: To estimate the incidence of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) compared with the general population in the USA. METHODS: This retrospective, longitudinal cohort study used data from an administrative claims database containing both commercial and Medicare Advantage Part D data, with a data period from October 2015 to February 2020. Patients were aged ≥ 18 years and divided into 2 cohorts: patients with RA and patients without RA. Diagnosis and procedure codes were used to identify HZ cases and calculate incidence rates (IRs) of HZ in the 2 cohorts. Data were stratified by age group (ie, 18-49, 18-29, 30-39, 40-49, 50-64, and ≥ 65 yrs) and RA therapy type. IR ratios (IRRs), adjusted by cohort baseline characteristics, were estimated using generalized linear models to compare the incidence of HZ between cohorts. RESULTS: The overall IR of HZ was higher in the RA cohort (21.5 per 1000 person-years [PY]; N = 67,650) than in the non-RA cohort (7.6 per 1000 PY; N = 11,401,743). The highest IRs in both cohorts were observed in the age group of ≥ 65 yrs (23.4 and 11.4 per 1000 PY in the RA cohort and non-RA cohort, respectively). The overall adjusted IRR of HZ was 1.93 (95% CI 1.87-1.99, P < 0.001) for the RA cohort compared with the non-RA cohort. In the RA cohort, the highest IRs by medication class were observed in patients using corticosteroids and those using Janus kinase inhibitors. CONCLUSION: These results highlight the increased incidence of HZ in patients with RA.

Rheumatoid Arthritis Disease Activity and Hospitalized Infection in a Large US Registry.

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.

Incidence of dementia in patients with rheumatoid arthritis and association with disease modifying anti-rheumatic drugs - Analysis of a national claims database.

OBJECTIVE: To evaluate the risk of incident dementia associated with the use of biologics or targeted synthetic DMARDs (b/tsDMARD) compared to conventional synthetic (cs) DMARDS only in patients with rheumatoid arthritis (RA). METHODS: We analyzed claims data from the Center for Medicare & Medicare Services (CMS) from 2006-2017. Patients with RA were identified as adults ≥40 years old and two RA diagnoses by a rheumatologist > 7 and < 365 days apart. Patients with a prior diagnosis of dementia were excluded. Use of cs/b/tsDMARDs was the exposure of interest. Person-time was classified as either: 1) b/tsDMARD exposed, which included tumor necrosis factor alpha inhibitors (TNFi)-bDMARDs, non-TNFi-bDMARDs or tsDMARDs with or without csDMARDs; 2) csDMARD-exposed: any csDMARD without b/tsDMARD. Patients could contribute time to different exposure groups if they changed medications. Incident dementia was defined as: 1 inpatient OR 2 outpatients ICD-9-CM or ICD-10 claims for dementia, OR prescription of a dementia-specific medication (rivastigmine, galantamine, memantine, donepezil, tacrine). Age-adjusted incident rates (IR) were calculated, and univariate and multivariate Cox proportional hazard models were used to calculate Hazard Ratios (HR) and 95% confidence intervals (CI). RESULTS: We identified 141,326 eligible RA patients; 80% female and 75.3% white, median age 67 years and mean (SD) exposure time of 1.1 (1.5) years. There were 233,271 initiations of c/b/tsDMARDS and 3,794 cases of incident dementia during follow up. The crude IR of dementia was 2.0 (95% CI 1.9-2.1) per 100 person-years for patients on csDMARDs and 1.3 (95% CI 1.2-1.4) for patients on any b/tsDMARD. Patients on b/tsDMARDs had an adjusted 19% lower risk for dementia than patients on csDMARDs [HR 0.81 (95% CI 0.76-0.87)]. Subgroup analysis found comparable risk reductions between TNFi, non-TNFi, and tsDMARDs. on the risk of dementia. CONCLUSIONS AND RELEVANCE: The incidence of dementia in patients with RA was lower in patients receiving b/tsDMARDs when compared to patients on csDMARD only. No differences were observed between different classes of b/tsDMARDs, suggesting that decreased risk is possibly explained by the overall decrease in inflammation rather than a specific mechanism of action of these drugs.

Comparing cardiovascular risk of patients with rheumatoid arthritis within the Social Security Disability Insurance with those commercially insured.

OBJECTIVE: To compare cardiovascular disease (CVD) rates in rheumatoid arthritis (RA) beneficiaries of the Social Security Disability Insurance (SSDI) with commercially insured RA patients. METHOD: We created three cohorts of RA patients aged < 65 years for SSDI and three for Marketscan using claims data from 2006 to 2016. The cohort definitions were as follows: (1) cohort 1: ≥ 2 diagnosis codes for RA occurring 7-365 days apart with ≥ 1 diagnosis code from a rheumatologist; (2) cohort 2: ≥ 1 diagnosis code for RA from a rheumatologist and a disease-modifying antirheumatic drugs (DMARDS); and (3) cohort 3: cohort 2, plus initiation of a new biologic/tofacitinib. We used Cox regression to determine the CVD risk comparing SSDI vs. Marketscan. Models were sequentially adjusted for age and sex (model 1); model 1 + diabetes, smoking, and high CVD risk (model 2); and model 2 + dual eligible (Medicare and Medicaid), subsidy, and state buy in (model 3). RESULTS: There were 380,336 RA patients, mean age 53.3 (SD 8.1) years, 21-24% male. Prevalence of comorbidities was higher in SSDI vs. Marketscan. SSDI RA patients in cohort 2 (model 3) had higher CVD risk (HR 1.23 (1.14-1.33). In cohort 3 (model 3), CVD risk was not statistically significantly different between SSDI and Marketscan (HR 0.89 (0.69-1.15). CONCLUSION: RA patient beneficiaries of the SSDI had higher risk for CVD events than those employed. The differences in CVD events between SSDI and Marketscan were partially attributable to differences in CVD risk factors.

Satisfaction with modes of telemedicine delivery during COVID-19: A randomized, single-blind, parallel group, noninferiority trial.

BACKGROUND: Little is known about satisfaction with different modes of telemedicine delivery. The objective of this study was to determine whether patient satisfaction with phone-only was noninferior to video visits. METHODS: We conducted a parallel group, randomized (1:1), single-blind, noninferiority trial in multispecialty clinics at a tertiary academic medical center. Adults age ≥ 60 years or with Medicare/Medicaid insurance were eligible. Primary outcome was visit satisfaction rate (9 or 10 on a 0-10 satisfaction scale). Noninferiority was determined if satisfaction with phone-only (intervention) versus video visits (comparator) was no worse by a -15% prespecified noninferiority margin. We performed modified intent-to-treat (mITT) and per protocol analyses, after adjusting for age and insurance. RESULTS: 200 participants, 43% Black, 68% women completed surveys. Visit satisfaction rates were high. In the mITT analysis, phone-only visits were noninferior by an adjusted difference of 3.2% (95% CI, -7.6% to 14%). In the per protocol analysis, phone-only were noninferior by an adjusted difference of -4.1% (95% CI, -14.8% to 6.6%). The proportion of participants who indicated they preferred the same type of telemedicine visit as their next clinic visit were similar (30.2% vs 27.9% video vs phone-only, p = 0.78) and a majority said their medical concerns were addressed and would recommend a telemedicine visit. CONCLUSIONS: Among a group of diverse, established older or underserved patients, the satisfaction rate for phone-only was noninferior to video visits. These findings could impact practice and policies governing telemedicine.

The Economic Benefit of Remission for Patients with Rheumatoid Arthritis.

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

Complement activation products vs standard ANA testing: Treatment outcomes, diagnosis, and economic impact (CAPSTONE) in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex clinical diagnosis historically aided by imperfect biomarkers. The advent of a multianalyte assay panel incorporating innovative cell-bound complement activation markers necessitates a comparison of its clinical utility to conventional autoantibodies for the diagnosis and treatment of SLE. OBJECTIVES: To compare the likelihood of SLE diagnosis, SLE treatment initiation, and the downstream impact on health care utilization among patients tested with AVISE Lupus (AVISE) vs standard-of-care laboratory testing with the traditional antinuclear antibody (ANA) testing strategy cohort (tANA). METHODS: An observational retrospective cohort study was conducted using electronic health record (EHR) data from the Illumination Health registry, which integrates EHR records from more than 300 rheumatologists across the US. Health records from January 2016 to December 2020 and administrative claims with cost data for a subset of patients linkable to the HealthCore Integrated Research Database and Medicare data were analyzed. The AVISE and tANA test results were classified as positive, negative, or indeterminate, and outcomes were stratified based on test results. Two cohorts were established: AVISE testing strategy and the tANA approach. Analyses included test impact on SLE diagnosis, treatment initiation, patterns of repeat testing, and downstream health care utilization. Multivariable logistic regression was used to estimate odds ratios (ORs) comparing the likelihood of SLE medication initiation and SLE diagnosis between the AVISE and tANA cohorts. RESULTS: The main cohort included 21,827 AVISE testing episodes and 22,778 tANA testing episodes. A total of 2,437 (11.2%) patients tested positive by AVISE compared with 5,364 (23.6%) of tANA positive patients. Among patients with no baseline prescription for SLE medication(s), patients with a positive AVISE test result were more likely to initiate SLE medications compared with tANA positive patients (43% vs 32%; OR = 1.57; 95% CI = 1.41-1.76). The treatment effect was larger in patients new to the practice within the preceding year (55% vs 33%; adjusted OR = 2.77; 95% CI = 2.31-3.32). AVISE positive patients were more than 5-fold more likely to be diagnosed with SLE, as compared with the tANA patients (31% vs 8%; OR = 5.11; 95% CI = 4.43-5.89), and similar in the new patient cohort (30% vs 6%; OR = 6.34; 95% CI = 5.12-7.86). Linked EHR-Medicare data revealed a greater decrease in posttest vs pretest mean annualized outpatient laboratory testing in AVISE negative (-$985; P < 0.0001) vs tANA negative (-$356; P < 0.0001) patients. A similar analysis in the EHR-HealthCore linked data revealed similar numerical trends as the Medicare data for outpatient laboratory testing but did not reach significance (P > 0.05). Cost comparisons in the categories of hospitalization, emergency department, outpatient imaging, and pharmacy costs did not yield significant differences. CONCLUSIONS: The significantly greater likelihood of SLE diagnosis and SLE medication initiation in AVISE positive vs tANA positive patients is consistent with improved clinical actionability, potentially shortening time to diagnosis. AVISE negative patients experienced a greater decrease in outpatient laboratory testing posttest relative to tANA negative patients, supporting the improved negative predictive value of AVISE vs tANA. DISCLOSURES: Mr O'Malley and Dr Zack are employed by Exagen Inc. Drs Curtis and Xie, Ms Su, and Ms Clinton are affiliated with the University of Alabama at Birmingham. Mr Haechung and Dr Grabner are employees of HealthCore, Inc., which received funding from Bendcare (owner of the Illumination Health Registry) for the conduct of parts of the study on which this manuscript is based. Exagen Inc. provided funding to Bendcare for the conduct of the study. Dr Grabner is also a shareholder of Anthem, Inc.

Recombinant Zoster Vaccine Uptake and Risk of Flares Among Older Adults With Immune-Mediated Inflammatory Diseases in the US.

OBJECTIVE: Persons with immune-mediated inflammatory diseases (IMIDs) are at an increased risk of herpes zoster (HZ). In 2018, the Centers for Disease Control and Prevention recommended a highly efficacious vaccine, recombinant zoster vaccine (RZV), for prevention of HZ in immunocompetent patients ≥50 years of age. This study was undertaken to estimate RZV vaccination among adults ages ≥50 years with IMIDs during 2018-2019 and to examine possible vaccine-related flares following RZV. METHODS: We identified a cohort of IMID patients using medical claims data from the IBM MarketScan (ages 50-64 years) and Centers for Medicare and Medicaid Services Medicare (ages ≥65 years) databases. Presumed flares were defined as hospitalization/emergency department visit for their respective IMIDs, or steroid treatment with a short-acting oral glucocorticoid or parenteral glucocorticoid injection. We conducted a self-controlled case series (SCCS) analysis to examine a temporal association between RZV and flares. RESULTS: Among enrollees with IMIDs, 14.8% of 55,654 MarketScan enrollees and 43.2% of 160,545 Medicare enrollees received ≥1 dose of RZV in 2018-2019. Two-dose series completion rates were 76.6% in MarketScan enrollees and 85.4% in Medicare enrollees. In the SCCS analysis, 10% and 13% developed flares in the control window, compared to 9% and 11-12% in the risk window following 1 or 2 doses of RZV among MarketScan and Medicare enrollees, respectively. We found no statistically significant increase in flares following RZV administration for any IMID in either age group following RZV dose 1 or dose 2. CONCLUSION: We did not find an increase in presumed flares following RZV vaccination. Among adults ages ≥50 years with IMIDs, a substantial proportion received RZV compared to general zoster coverage estimates, and series completion rates were high.

Protocol for the pilot randomized trial of the CArdiovascular Risk assEssment for Rheumatoid Arthritis (CARE RA) intervention: a peer coach behavioral intervention.

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of death among people with rheumatoid arthritis (RA), with an estimated increased risk of 50-60% compared to the general population. Lipid-lowering strategies have been shown to lower CVD risk significantly in people with RA and hyperlipidemia. Thus, CVD risk assessment has an important role to play in reducing CVD among people with RA. Yet currently only 37 to 45% of this population are receiving primary lipids screening. This paper describes the CArdiovascular Risk assEssment for RA (CARE RA) intervention, which is designed to address this issue. CARE RA is a peer coach intervention, that is, an intervention in which a person with RA coaches another person with RA, which is designed to educate people with RA about the relation between RA and CVD risk and to help them obtain evidence-based CVD risk assessment and treatment. METHODS: This is an open-label pilot study that will test if the participants assigned to complete the CARE RA curriculum with a peer coach will receive a cardiovascular risk assessment more frequently compared to those that complete the CARE RA curriculum by themselves. The CARE RA intervention is guided by Social Cognitive Theory. Participants in the peer coach intervention arm will receive the assistance of a peer coach who will call the participants once a week for 5 weeks to go over the CARE RA curriculum and train them on how to obtain CVD risk assessment. The control arm will complete the CARE RA curriculum without any assistance. Participants will be randomized 1:1 either to the control arm or to the peer coach intervention arm. The primary outcome is a participant's having a CVD risk assessment or initiating a statin, if indicated. Secondary outcomes include patient activation and RA medication adherence. The RE-AIM implementation framework guides the implementation and evaluation of the intervention. DISCUSSION: This pilot study will test the feasibility of the peer coach intervention in anticipation of a larger trial. CARE RA pioneers the use of peer coaches to facilitate the implementation of evidence-based treatment guidelines among people with RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT04488497 . Registered on July 28, 2020.

Risk of Serious Infection With Low-dose Glucocorticoids in Patients With Rheumatoid Arthritis: An Instrumental Variable Analysis.

BACKGROUND: Low-dose glucocorticoids are commonly used in the treatment of rheumatoid arthritis (RA). Observational studies have found an increased risk of serious infection associated with low-dose glucocorticoids, but concerns about residual confounding remain. METHODS: We identified adults with RA on stable immunomodulatory therapy for >6 months receiving no glucocorticoids or ≤5 mg/day using Medicare data from 2006 to 2015. We used provider preference for glucocorticoids as an instrumental variable (IV) to assess associations between low-dose glucocorticoid use and the risk of infection requiring hospitalization using a cause-specific proportional hazards model. RESULTS: We identified 163,603 qualifying treatment episodes among 120,656 patients. Glucocorticoids ≤5 mg/day were used by 25,373/81,802 (31.0%) of patients seen by a rheumatologist with low provider preference for glucocorticoids and by 36,087/81,801 (44.1%) of patients seen by a rheumatologist with high provider preference for glucocorticoids (adjusted odds ratio 1.81, 95% confidence interval 1.77, 1.84 for association between provider preference and glucocorticoids). Chronic obstructive pulmonary disease, opioids, antibiotics, previous emergency department visits, hospitalizations, and infections requiring hospitalization infections were unbalanced with regard to exposure but not to the IV. The incidence of infection requiring hospitalization was 8.0/100 person-years among patients unexposed to glucocorticoids versus 11.7/100 person-years among those exposed. The association between glucocorticoids and infection requiring hospitalization from IV analysis (hazard ratio 1.26 [1.02-1.56]) was similar to results from a standard multivariable model (hazard ratio 1.24 [1.21-1.28]). CONCLUSIONS: Among patients with RA on stable immunomodulatory therapy, IV analysis based on provider preference demonstrated an increased risk of infection requiring hospitalization associated with low-dose glucocorticoids, similar to a traditional analysis.

Tumor Necrosis Factor Inhibitors and the Risk of Cancer among Older Americans with Rheumatoid Arthritis.

BACKGROUND: TNF inhibitors (TNFi) effectively treat rheumatoid arthritis but may increase patient risk of some malignancies, particularly lymphomas or skin cancers. METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to conduct a case-control study in patients with rheumatoid arthritis (2007-2015). Cases were individuals with a first cancer diagnosed in SEER registries (ages 66-99, 22 cancer sites, N = 10,263). Skin cancer cases [nonmelanoma skin cancer (NMSC, N = 501), basal cell carcinoma (BCC, N = 161), squamous cell carcinoma (SCC, N = 150)] and cancer-free controls (N = 30,475) were selected from Medicare beneficiaries residing in SEER areas. Cases and controls had prior Medicare claims-based evidence for rheumatoid arthritis, and TNFi exposure was ascertained from part B and part D claims. Logistic regression was used to estimate adjusted odds ratios (aOR). RESULTS: TNFi exposure was present in 16.2% of controls and 12.8% to 33.7% of cancer cases, varying by site. TNFi use was associated with increased risk of NMSC overall (aOR 1.32, 95% confidence interval 1.06-1.63), non-Hodgkin lymphoma (NHL) overall (1.28, 1.06-1.56) and, specifically, follicular lymphoma (2.63, 1.63-4.24). TNFi exposure was not associated with other SEER cancer sites, BCC or SCC specifically, or other common NHL subtypes. CONCLUSIONS: Among older adults with rheumatoid arthritis, TNFi exposure was associated with elevated risk of NMSC and NHL, driven specifically by follicular lymphoma. Exposure was not associated with increased risk for other cancer sites. IMPACT: Our results support a role for TNF in lymphomagenesis. Given the association with NMSC, patients initiating TNFi therapy may benefit from skin cancer screening and sun protection measures.

Comparative effectiveness of biologics and targeted therapies for psoriatic arthritis.

OBJECTIVE: To 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). METHODS: We 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. RESULTS: Of 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). CONCLUSIONS: TNF-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.