Patterns of Bisphosphonates Utilization in Patients under Age 45 in a Large Cohort of Commercial Insurance Beneficiaries in the United States

Background: The effectiveness and safety of bisphosphonates treatment used in the young population have not been well studied. Despite insufficient data on effectiveness and safety of bisphosphonates in young patients, bisphosphonates are still considered in younger patients at high risk for osteoporosis or fracture. The objectives of this study were to identify bisphosphonate initiators aged 10–45 years and describe their clinical characteristics and to assess time trends of bisphosphonate use over the past decade in a large U.S. population-based cohort. Methods: Using the medical and pharmacy claims data from a U.S. commercial insurance (2003–2012), patients aged 10–45 years without malignancy who initiated an oral or intravenous bisphosphonate after at least 1 year of insurance enrollment were selected. Baseline demographics, comorbidities, medications and health care utilization were assessed in the year prior to initiating a bisphosphonate. The trend of bisphosphonate use over time was examined. Results: There were 9,082 bisphosphonate initiators (0.02% of the same age group in the population). The mean age was 38.1 years and 79.6% female. Osteoporosis was the most common diagnosis (41.2%). At baseline, 10.8% had a diagnosis of fracture and 29.0% had a bone mineral density measured. Of those who used glucocorticoids (39%) at baseline, the mean 1-year cumulative prednisone-equivalent dose was 2,669 milligrams. The use of bisphosphonates in the young population significantly decreased over the past decade (p<0.001). Conclusions: Among young patients aged 10–45, the use of bisphosphonates was uncommon and significantly decreased over the past decade in the U.S. While most patients initiating bisphosphonates had a diagnosis of osteoporosis and fracture in the preceding year, some had no recorded claims with a diagnosis of fracture, osteoporosis, or long-term glucocorticoids use at baseline. Future research is needed to examine the effectiveness and safety of bisphosphonates in young patients at risk for osteoporosis

The sequence of disease-modifying anti-rheumatic drugs: pathways to and predictors of tocilizumab monotherapy

Background: There are numerous non-biologic and biologic disease-modifying anti-rheumatic drugs (bDMARDs) for rheumatoid arthritis (RA). Typical sequences of bDMARDs are not clear. Future treatment policies and trials should be informed by quantitative estimates of current treatment practice. Methods: We used data from Corrona, a large real-world RA registry, to develop a method for quantifying sequential patterns in treatment with bDMARDs. As a proof of concept, we study patients who eventually use tocilizumab monotherapy (TCZm), an IL-6 antagonist with similar benefits used as monotherapy or in combination. Patients starting a bDMARD were included and were followed using a discrete-state Markov model, observing changes in treatments every 6\ua0months and determining whether they used TCZm. A supervised machine learning algorithm was then employed to determine longitudinal patient factors associated with TCZm use. Results: 7300 patients starting a bDMARD were followed for up to 5 years. Their median age was 58 years, 78% were female, median disease duration was 5 years, and 57% were seropositive. During follow-up, 287 (3.9%) reported use of TCZm with median time until use of 25.6 (11.5, 56.0) months. Eighty-two percent of TCZm use began within 3\ua0years of starting any bDMARD. Ninety-three percent of TCZm users switched from TCZ combination, a TNF inhibitor, or another bDMARD. Very few patients are given TCZm as their first DMARD (0.6%). Variables associated with the use of TCZm included prior use of TCZ combination therapy, older age, longer disease duration, seronegative, higher disease activity, and no prior use of a TNF inhibitor. Conclusions: Improved understanding of treatment sequences in RA may help personalize care. These methods may help optimize treatment decisions using large-scale real-world data

Combined Conventional Synthetic Disease Modifying Therapy vs. Infliximab for Rheumatoid Arthritis : Emulating a Randomized Trial in Observational Data

Funding Information: This work was supported by the Swedish Research Council (grant 2016‐01355). S.C.K. is supported by the National Institutes of Health (NIH; grant K24AR078959). Publisher Copyright: © 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.Observational studies are often considered unreliable for evaluating relative treatment effectiveness, but it has been suggested that following target trial protocols could reduce bias. Using observational data from patients with rheumatoid arthritis (RA) in the Swedish Rheumatology Quality Register (SRQ), between 2006 and 2020, we emulated the protocol of the Swedish Farmacotherapy trial (SWEFOT) and compared the results. SWEFOT was a pragmatic trial nested in SRQ, between 2002 and 2005, where methotrexate (MTX) insufficient responders were randomized to receive additional infliximab or sulfasalazine (SSZ) + hydroxychloroquine (HCQ). Patients with RA initiating infliximab (N = 313) or SSZ + HCQ (N = 196) after MTX were identified in SRQ and the Prescribed Drugs Register, mimicking the SWEFOT eligibility criteria. The primary outcome was the proportion of European Alliance of Associations for Rheumatology (EULAR) good responders at 9 months, classifying patients who discontinued treatment as “nonresponders.” Through sensitivity analyses, we assessed the impact of relaxing eligibility criteria. The observed proportions reaching EULAR good response were close to those reported in SWEFOT: 39% (vs. 39% in SWEFOT) for infliximab and 28% (vs. 25%) for SSZ + HCQ. The crude observed response ratio was 1.39 (95% confidence interval (CI) 1.04–1.86), increasing to 1.48 (95% CI 0.98–2.24) after confounding adjustment, compared to 1.59 (95% CI 1.10–2.30) in SWEFOT. Results remained close to SWEFOT when relaxing eligibility criteria until allowing prior disease-modifying anti-rheumatic drug (DMARD) use which reduced the observed difference between treatments. By applying a prespecified trial emulation protocol to observational clinical registry data, we could replicate the results of SWEFOT, favoring infliximab over SSZ + HCQ combination therapy at 9 months.Peer reviewe

Comparative Cardiovascular Risk of Abatacept and Tumor Necrosis Factor Inhibitors in Patients With Rheumatoid Arthritis With and Without Diabetes Mellitus: A Multidatabase Cohort Study

Background: We examined the cardiovascular risk of abatacept compared with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis with and without diabetes mellitus (DM). Methods and Results: We conducted a cohort study of patients with rheumatoid arthritis who newly started abatacept or TNF inhibitors using claims data from Medicare and MarketScan. The primary outcome was a composite cardiovascular end point of myocardial infarction (MI), stroke/transient ischemic attack, and coronary revascularization. To account for >60 baseline characteristics, abatacept initiators were 1:1 propensity score (PS) matched to TNF initiators in each database. Cox proportional hazards models estimated hazard ratio (HR) and 95% confidence interval (CI) in the PS‐matched cohort per database. A fixed‐effects meta‐analysis pooled database‐specific HRs. We included a total of 13 039 PS‐matched pairs of abatacept and TNF inhibitor initiators (6103 pairs in Medicare and 6936 pairs in MarketScan). A total of 34.7% in Medicare and 19.8% in MarketScan had baseline DM. The HR (95% CI) for the primary outcome associated with abatacept use versus TNF inhibitor was 0.81 (0.66–0.99) in Medicare and 0.95 (0.74–1.23) in MarketScan, with a pooled HR of 0.86 (95% CI, 0.73–1.01; P=0.3 for heterogeneity). The risk of the primary outcome was lower in abatacept initiators versus TNF inhibitors in the DM subgroup, with a pooled HR of 0.74 (95% CI, 0.57–0.96; P=0.7 for heterogeneity), but not in the non‐DM subgroup, with a pooled HR of 0.94 (95% CI, 0.77–1.14; P=0.4 for heterogeneity). Conclusions: In this large population‐based cohort of patients with rheumatoid arthritis, abatacept use appeared to be associated with a modestly reduced cardiovascular risk when compared with TNF inhibitor use, particularly in patients with DM

Sociodemographic, Disease, Health System, and Contextual Factors Affecting the Initiation of Biologic Agents in Rheumatoid Arthritis: A Longitudinal Study: Factors Influencing Initiation of Biologic Agents in RA

To analyze the effect of sociodemographic, disease, and health system characteristics and contextual features about the community of residence on the subsequent initiation of treatment with biologic agents for rheumatoid arthritis (RA)

Association between inflammation and systolic blood pressure in RA compared to patients without RA

Background: The relationship between inflammation and blood pressure (BP) has been studied mainly in the general population. In this study, we examined the association between inflammation and BP across a broader range of inflammation observed in rheumatoid arthritis (RA) and non-RA outpatients. Methods: We studied subjects from a tertiary care outpatient population with C-reactive protein (CRP) and BP measured on the same date in 2009–2010; RA outpatients were identified using a validated algorithm. General population data were obtained from the National Health and Nutrition Examination Survey (NHANES) as comparison. To study the cross-sectional association between CRP and BP in the three groups, we constructed a generalized additive model. Longitudinal association between CRP and BP was examined using a repeated-measures linear mixed-effects model in RA outpatients with significant change in inflammation at two consecutive time points. Results: We studied 24,325 subjects from the outpatient population, of whom 1811 had RA, and 5561 were from NHANES. In RA outpatients, we observed a positive relationship between CRP and systolic BP (SBP) at CRP < 6 mg/L and an inverse association at CRP ≥ 6 mg/L. A similar inverse U-shaped relationship was observed in non-RA outpatients. In NHANES, we observed a positive relationship between CRP and SBP as demonstrated by previous studies. Longitudinal analysis in RA showed that every 10 mg/L increase in CRP was associated with a 0.38 mmHg reduction in SBP. Conclusions: Across a broad range of CRP observed in RA and non-RA outpatients, we found an inverse U-shaped relationship between CRP and SBP, highlighting a relationship not previously observed when studying the general population. Electronic supplementary material The online version of this article (10.1186/s13075-018-1597-9) contains supplementary material, which is available to authorized users

2020 American College of Rheumatology Guideline for the Management of Gout

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155484/1/art41247.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155484/2/art41247_am.pd

New Era of Air Quality Monitoring from Space: Geostationary Environment Monitoring Spectrometer (GEMS)

GEMS will monitor air quality over Asia at unprecedented spatial and temporal resolution from GEO for the first time, providing column measurements of aerosol, ozone and their precursors (nitrogen dioxide, sulfur dioxide and formaldehyde). Geostationary Environment Monitoring Spectrometer (GEMS) is scheduled for launch in late 2019 - early 2020 to monitor Air Quality (AQ) at an unprecedented spatial and temporal resolution from a Geostationary Earth Orbit (GEO) for the first time. With the development of UV-visible spectrometers at sub-nm spectral resolution and sophisticated retrieval algorithms, estimates of the column amounts of atmospheric pollutants (O3, NO2, SO2, HCHO, CHOCHO and aerosols) can be obtained. To date, all the UV-visible satellite missions monitoring air quality have been in Low Earth orbit (LEO), allowing one to two observations per day. With UV-visible instruments on GEO platforms, the diurnal variations of these pollutants can now be determined. Details of the GEMS mission are presented, including instrumentation, scientific algorithms, predicted performance, and applications for air quality forecasts through data assimilation. GEMS will be onboard the GEO-KOMPSAT-2 satellite series, which also hosts the Advanced Meteorological Imager (AMI) and Geostationary Ocean Color Imager (GOCI)-2. These three instruments will provide synergistic science products to better understand air quality, meteorology, the long-range transport of air pollutants, emission source distributions, and chemical processes. Faster sampling rates at higher spatial resolution will increase the probability of finding cloud-free pixels, leading to more observations of aerosols and trace gases than is possible from LEO. GEMS will be joined by NASA&apos;s TEMPO and ESA&apos;s Sentinel-4 to form a GEO AQ satellite constellation in early 2020s, coordinated by the Committee on Earth Observation Satellites (CEOS)