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1.
Ann Rheum Dis ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568386

RESUMO

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

2.
ACR Open Rheumatol ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33570829

RESUMO

OBJECTIVE: Vascular ultrasound (VUS) is a first-line test for giant cell arteritis (GCA) in Europe but has been of limited use in the United States. We report clinical experience with a multidisciplinary model of VUS for the evaluation of GCA at a large US medical center. METHODS: Patients who underwent VUS for evaluation of GCA between 2013 and 2017 were reviewed. Trained vascular technologists followed a standardized protocol to visualize bilateral temporal, carotid, subclavian, and axillary arteries. Vascular medicine physicians interpreted VUS as no arteritis, hyperechoic wall thickening, or acute arteritis. Characteristics of patients with versus without acute arteritis (no arteritis or hyperechoic wall thickening) were compared. Among patients with suspected new-onset GCA, the treating physician's pretest and posttest suspicion for GCA were compared. RESULTS: Of 530 patients, 10.6% had prior-onset GCA, 31.7% had polymyalgia rheumatica, and 57.6% were taking glucocorticoids. Most patients had no arteritis on VUS (84.3%); 10.6% had acute arteritis, and 5.1% had hyperechoic wall thickening. Typical GCA symptoms, such as jaw claudication and scalp tenderness, were significantly more frequent in patients with acute arteritis. For all 42 patients with suspected new-onset GCA and acute arteritis, posttest suspicion was unchanged or increased. Of 415 patients with suspected new-onset GCA and VUS without acute arteritis, suspicion decreased (76.4%) or was unchanged (20.2%). CONCLUSION: We describe a multidisciplinary model for incorporating VUS into GCA care. When pretest suspicion was low and VUS did not reveal acute arteritis, posttest suspicion typically decreased, whereas when pretest suspicion was high and VUS revealed acute arteritis, posttest suspicion was reinforced.

3.
ACR Open Rheumatol ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33491920

RESUMO

OBJECTIVE: The objective of this study was to validate claims-based algorithms for identifying acute giant cell arteritis (GCA) that will help generate real-world evidence on comparative effectiveness research and epidemiologic studies. Among patients identified by the GCA algorithm, we further investigated whether GCA flares could be detected by using claims data. METHODS: We developed five claims-based algorithms based on a combination of International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes, specialist visits, and dispensed medications using Medicare Parts A, B, and D linked to electronic medical records (2006-2014). Acute cases of GCA were determined by chart review using the treating physician's diagnosis of GCA as the gold standard. Among the patients identified with acute GCA, we assessed if a GCA flare occurred during the year after initial diagnosis. RESULTS: The number of patients identified by each algorithm ranged from 220 to 896. Positive predictive values (PPVs) of the algorithms ranged from 60.7% to 84.8%. Requirement for disease-specific workups, multiple diagnosis codes, or specialist visits improved the PPVs. The highest PPV (84.8%) was noted in an algorithm that required two or more diagnosis codes of GCA from inpatient, emergency department, or outpatient rheumatology visits plus a prednisone-equivalent dose greater than or equal to 40 mg/day occurring 14 days before or after the second ICD-9 diagnosis date, with the cumulative days' supply greater than or equal to 14 days. Among patients identified as having GCA, 18.2% of patients had definite evidence of a flare and 25% had a potential flare. CONCLUSION: A claims-based algorithm requiring two or more ICD-9 diagnosis codes from inpatient, emergency department, or outpatient rheumatology visits and high-dose glucocorticoid dispensing can be a useful tool to identify acute GCA cases in large administrative claims databases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33461759

RESUMO

INTRODUCTION: Although calcium pyrophosphate deposition (CPPD) disease is common, there are no validated outcome measures for clinical research in this condition. The aim of this study was to generate a list of outcome domains as reported by patients, their caregivers, healthcare professionals (HCPs) and stakeholders to inform the development of an Outcome Measures in Rheumatology (OMERACT) Core Domain Set for CPPD. METHODS: Patients with CPPD and their caregivers, HCPs and stakeholders took part in semi-structured qualitative interviews to explore potential outcome domains for CPPD clinical research relevant to their lived experience and knowledge of CPPD. Interviews were conducted in six countries across three continents. Data was analysed using manifest content analysis to identify outcome domains, which were tabulated and mapped to the core areas as defined by the OMERACT Filter 2.1. RESULTS: Thirty-six interviews were conducted in total. Participants comprised of 28 patients (six of which included a caregiver), seven HCPs and one stakeholder. The commonly identified (sub-) domains (d) across the 1) abnormalities/manifestations core area were joint pain (d = 35), joint swelling (d = 27), joint stiffness (d = 25), CPPD flares (d = 25); 2) life-impact core area were overall function (d=35), and specifically the ability to complete daily tasks (d = 25); and 3) societal/resource use core area were use of analgesic medicines (d = 26). Patients more commonly reported joint swelling, stiffness and range of movement, and use of analgesics while HCPs more commonly reported domains relating to presence of CPP crystals, radiologic calcification, joint damage, time to diagnosis and suitability of treatment. CONCLUSION: Among a number of potential outcome domains identified, articular manifestations, function and analgesic use were most frequently mentioned by participants. These findings will be used to develop an OMERACT Core Domain Set for CPPD.

5.
Ann Rheum Dis ; 79(10): 1333-1339, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32816709

RESUMO

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Seleção de Pacientes , Sensibilidade e Especificidade
6.
Ann Intern Med ; 173(7): 516-526, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32716706

RESUMO

BACKGROUND: Denosumab is effective for osteoporosis, but discontinuation leads to rapid reversal of its therapeutic effect. OBJECTIVE: To estimate the risk for fracture among users of denosumab who delayed subsequent doses compared with users who received doses on time. DESIGN: Population-based cohort study. SETTING: The Health Improvement Network U.K. primary care database, 2010 to 2019. PATIENTS: Persons aged 45 years or older who initiated denosumab therapy for osteoporosis. MEASUREMENTS: Observational data were used to emulate an analysis of a hypothetical trial with 3 dosing intervals: subsequent denosumab injection given within 4 weeks after the recommended date ("on time"), delay by 4 to 16 weeks ("short delay"), and delay by more than 16 weeks ("long delay"). The primary outcome was a composite of all fracture types at 6 months after the recommended date. Secondary outcomes were major osteoporotic fracture, vertebral fracture, hip fracture, and nonvertebral fracture. RESULTS: Investigators identified 2594 patients initiating denosumab therapy. The risk for composite fracture over 6 months was 27.3 in 1000 for on-time dosing, 32.2 in 1000 for short delay, and 42.4 in 1000 for long delay. Compared with on-time injections, short delay had a hazard ratio (HR) for composite fracture of 1.03 (95% CI, 0.63 to 1.69) and long delay an HR of 1.44 (CI, 0.96 to 2.17) (P for trend = 0.093). For vertebral fractures, short delay had an HR of 1.48 (CI, 0.58 to 3.79) and long delay an HR of 3.91 (CI, 1.62 to 9.45). LIMITATION: Dosing schedules were not randomly assigned. CONCLUSION: Although delayed administration of subsequent denosumab doses by more than 16 weeks is associated with increased risk for vertebral fracture compared with on-time dosing, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with long delay. PRIMARY FUNDING SOURCE: National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation.

7.
J Rheumatol ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669445

RESUMO

OBJECTIVE: Being overweight or obese increases rheumatoid arthritis (RA) risk among women, particularly among those diagnosed at a younger age. Abdominal obesity may contribute to systemic inflammation more than general obesity; thus, we investigated whether abdominal obesity, compared to general obesity, predicted RA risk in 2 prospective cohorts: the Nurses' Health Study (NHS) and NHS II. METHODS: We followed 50,682 women (1986-2014) in NHS and 47,597 women (1993-2015) in NHS II, without RA at baseline. Waist circumference (WC), BMI, health outcomes, and covariate data were collected through biennial questionnaires. Incident RA cases and serologic status were identified by chart review. We examined the associations of WC and BMI with RA risk using time-varying Cox proportional hazards models. We repeated analyses restricted to age ≤ 55 years. RESULTS: During 28 years of follow-up, we identified 844 incident RA cases (527 NHS, 317 NHS II). Women with WC > 88 cm (35 in) had increased RA risk (HR 1.22, 95% CI 1.06-1.41). A similar association was observed for seropositive RA, which was stronger among young and middle-aged women. Further adjustment for BMI attenuated the association to null. In contrast, BMI was associated with RA (HRBMI ≥ 30 vs < 25 1.33, 95% CI 1.05-1.68) and seropositive RA, even after adjusting for WC, and, as in WC analyses, this association was stronger among young and middle-aged women. CONCLUSION: Abdominal obesity was associated with increased RA risk, particularly for seropositive RA, among young and middle-aged women; however, it did not independently contribute to RA risk beyond general obesity.

8.
Clin Exp Rheumatol ; 38 Suppl 124(2): 107-111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32359038

RESUMO

OBJECTIVES: Literature describing follow-up vascular ultrasound (VUS) in giant cell arteritis (GCA) is limited. We report our experience with follow-up VUS obtained in clinical care of patients with GCA. METHODS: We retrospectively identified GCA patients with an abnormal initial VUS, defined as circumferential hypoechoic wall thickening ("halo sign"), or circumferential hyperechoic wall thickening without evidence of arteriosclerosis or arteritis, who subsequently underwent follow-up VUS during 2013-2018. Studies were interpreted as active arteritis, hyperechoic wall thickening without active arteritis, or no arteritis. We compared clinical and laboratory characteristics at time of initial VUS among patients with active arteritis vs. hyperechoic wall thickening without active arteritis. We described whether and how VUS interpretation changed from initial to follow-up VUS. Among individual vessels, we tested whether abnormal findings (e.g. halo sign) persisted at follow-up VUS using McNemar's test. RESULTS: 42 patients fulfilled study criteria. Median time between initial and follow-up VUS was 5.1 (IQR 2.6-7.9) months. Characteristics at initial VUS did not differ according to VUS interpretation. Among 36 patients with active arteritis on initial VUS, follow-up VUS showed active arteritis in 25.0%, hyperechoic wall thickening in 33.3% and no arteritis in 41.7%. Among 6 patients with hyperechoic wall thickening on initial VUS, half had no arteritis on follow-up VUS. Sonographic findings tended to persist in axillary arteries and were more likely to change in the superficial temporal arteries. CONCLUSIONS: Among 42 GCA patients, the majority had a change in VUS interpretation between initial and follow-up VUS. Sonographic findings in the temporal circulation more frequently changed than findings in axillary arteries.


Assuntos
Arterite de Células Gigantes/diagnóstico por imagem , Ultrassonografia , Artéria Axilar/diagnóstico por imagem , Artéria Axilar/patologia , Seguimentos , Arterite de Células Gigantes/patologia , Humanos , Estudos Retrospectivos , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/patologia
9.
Rheumatology (Oxford) ; 59(11): 3369-3379, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32310291

RESUMO

OBJECTIVES: RA develops slowly over years. We tested for metabolic changes prior to RA onset using a large non-targeted metabolomics platform to identify novel pathways and advance understanding of RA development. METHODS: Two hundred and fifty-four incident RA cases with plasma samples drawn pre-RA onset in the Nurses' Health Study (NHS) cohorts were matched 1:2 to 501 controls on age, race, menopause/post-menopausal hormone use and blood collection features. Relative abundances of 360 unique, known metabolites were measured. Conditional logistic regression analyses assessed associations between metabolites and incidence of RA, adjusted for age, smoking and BMI, accounting for multiple comparisons. Subgroup analyses investigated seropositive (sero+) RA and RA within 5 years of sample collection. Significant metabolites were then tested in a female military pre-RA case-control study (n = 290). RESULTS: In the NHS, metabolites associated with RA and sero+RA in multivariable models included 4-acetamidobutanoate (odds ratio (OR) = 0.80/S.d., 95% CI: 0.66, 0.95), N-acetylputrescine (OR = 0.82, 95% CI: 0.69, 0.96), C5 carnitine (OR = 0.84, 95% CI: 0.71, 0.99) and C5:1 carnitine (OR = 0.81, 95% CI: 0.68, 0.95). These were involved primarily in polyamine and leucine, isoleucine and valine metabolism. Several metabolites associated with sero+RA within 5 years of diagnosis were replicated in the independent military cohort: C5 carnitine (OR = 0.55, 95% CI: 0.33, 0.92), C5:1 carnitine (OR = 0.62, 95% CI: 0.39, 0.99) and C3 carnitine (OR = 0.57, 95% CI: 0.36, 0.91). CONCLUSION: Several metabolites were inversely associated with incidence of RA among women. Three short-chain acylcarnitines replicated in a smaller dataset and may reflect inflammation in the 5-year period prior to sero+RA diagnosis.

10.
Arthritis rheumatol. (Malden. Online) ; 72(4): [461-488], Apr. 4, 2020.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1117247

RESUMO

To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancyassessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). We conducted a systematic review of evidence relating to contraception, ART, fertility preservation,HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process todetermine final recommendations and grade their strength (conditional or strong). Good practice statements wereagreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.. This American College of Rheumatology guideline provides 12 ungraded good practice statements and131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended toguide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSBantibodies. Recommendations and good practice statements support several guiding principles: use of safe andeffective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physicianpatient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to the recommendations within this guideline to be voluntary, with the ultimate determination regarding their application to be made by the clinician in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes, but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision, as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions. These recommendations cannot adequately convey all uncertainties and nuances of patient care. The American College of Rheumatology is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service. This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.


Assuntos
Humanos , Doenças Reumáticas/prevenção & controle , Doenças Reumáticas/terapia , Doenças Musculoesqueléticas/prevenção & controle , Doenças Musculoesqueléticas/terapia , Saúde Reprodutiva
11.
Arthritis Care Res (Hoboken) ; 72(4): 461-488, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32090466

RESUMO

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.


Assuntos
Anticoncepção/métodos , Preservação da Fertilidade/métodos , Doenças Musculoesqueléticas/fisiopatologia , Saúde Reprodutiva , Doenças Reumáticas/fisiopatologia , Reumatologia/normas , Antirreumáticos/uso terapêutico , Feminino , Humanos , Masculino , Doenças Musculoesqueléticas/tratamento farmacológico , Gravidez , Doenças Reumáticas/tratamento farmacológico , Estados Unidos
12.
Arthritis Rheumatol ; 72(4): 529-556, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32090480

RESUMO

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.


Assuntos
Anticoncepção , Preservação da Fertilidade , Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Gerenciamento Clínico , Humanos , Saúde Reprodutiva , Reumatologia/normas
13.
Arthritis Rheumatol ; 2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32090491

RESUMO

OBJECTIVE: To compare achievement of remission in two early rheumatoid arthritis (RA) treat-to-target (TTT) cohorts, one tight control cohort targeting stringent remission in a randomized controlled strategy trial and one observational cohort targeting a looser definition of remission in clinical practice. METHODS: We analyzed data from the ARCTIC trial and the NOR-VEAC observational study. Both were Norwegian multicenter studies including disease modifying anti-rheumatic drug (DMARD)-naïve RA-patients and implementing TTT. The target in ARCTIC was remission defined as a Disease Activity Score (DAS44) <1.6 plus 0 of 44 swollen joint count, while the target in NOR-VEAC was the less stringent remission of DAS28<2.6. We assessed achievement of the study-specific targets and compared achievement of the ACR/ EULAR Boolean remission during two years of follow-up. RESULTS: We included 189 patients from ARCTIC and 330 patients from NOR-VEAC. More than half in each cohort had reached the study-specific target at 6 months, increasing to more than 60% at 12 and 24 months. The odds of reaching ACR/EULAR Boolean remission during follow-up were higher in ARCTIC than in NOR-VEAC, with statistically significant differences at 3 months (OR 1.73; 95% CI 1.03-2.89), 12 months (OR 1.97; 95% CI 1.21-3.20) and 24 months (OR 1.82; 95% CI 1.05 - 3.16). CONCLUSION: A majority of patients in both cohorts reached the study-specific treatment targets. More patients in ARCTIC than in NOR-VEAC achieved ACR/EULAR Boolean remission during follow-up, suggesting that targeting a more stringent definition of remission provide further potential for favorable outcomes of a TTT strategy.

14.
Ann Intern Med ; 172(6): 369-380, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066146

RESUMO

Background: Low-dose methotrexate (LD-MTX) is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis. Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred. Objective: To investigate AE rates, risk, and risk differences comparing LD-MTX versus placebo. Design: Prespecified secondary analyses of a double-blind, placebo-controlled, randomized trial. (ClinicalTrials.gov: NCT01594333). Setting: North America. Participants: Adults with known cardiovascular disease and diabetes or metabolic syndrome. Intervention: Random allocation to LD-MTX (≤20 mg/wk) or placebo. All participants received folic acid, 1 mg/d, 6 days per week. Measurements: Risks for specific AEs of interest, as well as for all AEs, were compared across treatment groups after blinded adjudication. Results: After an active run-in period, 6158 patients were enrolled and 4786 randomly assigned to a group; median follow-up was 23 months and median dosage 15 mg/wk. Among the randomly assigned participants, 81.2% were male, median age was 65.7 years, and median body mass index was 31.5 kg/m2. Of 2391 participants assigned to LD-MTX, 2080 (87.0%) had an AE of interest, compared with 1951 of 2395 (81.5%) assigned to placebo (hazard ratio [HR], 1.17 [95% CI, 1.10 to 1.25]). The relative hazards of gastrointestinal (HR, 1.91 [CI, 1.75 to 2.10]), pulmonary (HR, 1.52 [CI, 1.16 to 1.98]), infectious (HR, 1.15 [CI, 1.01 to 1.30]), and hematologic (HR, 1.15 [CI, 1.07 to 1.23]) AEs were elevated for LD-MTX versus placebo. With the exception of increased risk for skin cancer (HR, 2.05 [CI, 1.28 to 3.28]), the treatment groups did not differ in risk for other cancer or mucocutaneous, neuropsychiatric, or musculoskeletal AEs. Renal AEs were reduced in the LD-MTX group (HR, 0.85 [CI, 0.78 to 0.93]). Limitation: The trial was done in patients without rheumatic disease who tolerated LD-MTX during an active run-in period. Conclusion: Use of LD-MTX was associated with small to moderate elevations in risks for skin cancer and gastrointestinal, infectious, pulmonary, and hematologic AEs, whereas renal AEs were decreased. Primary Funding Source: National Institutes of Health.


Assuntos
Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Estudos Prospectivos
15.
Artigo em Inglês | MEDLINE | ID: mdl-31910317

RESUMO

OBJECTIVE: Identifying pseudogout in large datasets is difficult due to its episodic nature and lack of billing codes specific to this acute subtype of calcium pyrophosphate (CPP) deposition disease. We evaluated a novel machine learning approach for classifying pseudogout using electronic health record (EHR) data. METHODS: We created an EHR data mart of patients with ≥1 relevant billing code or ≥2 natural language processing (NLP) mentions of pseudogout or chondrocalcinosis, 1991-2017. We selected 900 for gold standard chart review for: (1) definite pseudogout, synovitis+synovial fluid CPP crystals; (2) probable pseudogout, synovitis+chondrocalcinosis; (3) not pseudogout. We applied a topic modeling approach to identify definite/probable pseudogout. A combined algorithm included topic modeling plus manually-reviewed CPP crystal results. We compared algorithm performance and cohorts identified by: (1) billing codes, (2) presence of CPP crystals, (3) topic modeling, (4) combined algorithm. RESULTS: Among 900 subjects, 123 (13.7%) had pseudogout by chart review (68 definite, 55 probable). Billing codes had sensitivity 65% and PPV 22% for pseudogout. Presence of CPP crystals had sensitivity 29% and PPV 92%. Without using CPP crystal results, topic modeling had sensitivity 29% and PPV 79%. The combined algorithm yielded sensitivity 42% and PPV 81%. The combined algorithm identified 50% more patients than presence of CPP crystals; the latter captured a portion of definite pseudogout and missed probable pseudogout. CONCLUSION: For pseudogout, an episodic disease with no specific billing code, combining NLP, machine learning methods, and synovial fluid lab results yielded an algorithm that significantly boosted PPV compared to billing codes.

16.
J Clin Endocrinol Metab ; 105(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894244

RESUMO

CONTEXT: Discontinuation of denosumab leads to a rapid reversal of its therapeutic effect. However, there are no data regarding how unintended delays or missed injections of denosumab impact bone mineral density (BMD) response. OBJECTIVE: We examined the association of delays in injections of denosumab with BMD change. DESIGN: We used electronic medical records from two academic hospitals from 2010 to 2017. PARTICIPANTS: Patients older than 45 years of age and used at least 2 doses of 60 mg denosumab. Denosumab adherence was evaluated by the medication coverage ratio (MCR). Good adherence corresponds to a dosing interval ≤7 months (defined by MCR ≥93%), moderate adherence corresponds to an interval of 7 to 10 months (MCR 75%-93%), and poor adherence corresponds to an interval ≥10 months (MCR ≤75%). OUTCOME MEASURES: Annualized percent BMD change from baseline at the lumbar spine, total hip, and femoral neck. RESULTS: We identified 938 denosumab injections among 151 patients; the mean (SD) age was 69 (10) years, and 95% were female. Patients with good adherence had an annualized BMD increase of 3.9% at the lumbar spine, compared with patients with moderate (3.0%) or poor adherence (1.4%, P for trend .002). Patients with good adherence had an annualized BMD increase of 2.1% at the total hip, compared with patients with moderate (1.3%) or poor adherence (0.6%, P for trend .002). CONCLUSIONS: A longer interval between denosumab injections is associated with suboptimal BMD response at both spine and total hip. Strategies to improve the timely administration of denosumab in real-world settings are needed.

17.
Arthritis Care Res (Hoboken) ; 72(12): 1820-1826, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31560454

RESUMO

OBJECTIVE: A project aimed at developing new classification criteria for systemic lupus erythematosus (SLE) is based on weighted criteria that include both laboratory and clinical items. Combinations of certain symptoms may occur commonly in SLE, which provides an argument against independently counting these items. The current study was undertaken to evaluate the interrelationship between candidate criteria items in the International Early SLE cohort and in the Euro-Lupus cohort. METHODS: The International Early SLE cohort included 389 patients, who were diagnosed within 3 years prior to the study. Data on the ACR's 1997 update of the SLE revised criteria, the Systemic Lupus International Collaborating Clinics 2012 criteria, and on 30 additional items were collected. To evaluate the interrelationship of the criteria, a tetrachoric correlation was used to assess the degree of association between different manifestations in the same organ system. The correlations identified in the International Early SLE cohort were validated in the Euro-Lupus cohort. RESULTS: A few relevant correlations were observed among specific clinical cutaneous manifestations (in particular, malar rash correlated with photosensitivity, alopecia, and oral ulcers) and serologic manifestations (anti-Sm and anti-double-stranded DNA and anti-RNA polymerase, anti-Ro and anti-La, and antiphospholipid antibodies), and these results were validated in the Euro-Lupus cohort. The associations within the mucocutaneous domain, hematologic and the specific autoantibodies suggest that within a single domain only the highest ranking item should be counted to avoid overrepresentation. CONCLUSION: Some of the candidate SLE criteria cluster within domains. Given these interrelationships, multiple criteria within a domain should not be independently counted. These results are important to consider for the structure of new SLE classification criteria.

18.
Arthritis Care Res (Hoboken) ; 72(4): 591-599, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30762311

RESUMO

OBJECTIVE: Observational data facilitate examination of treatment-effect heterogeneity, but the risk of bias is substantial. The present study was undertaken to highlight methodologic considerations through an analysis of whether smoking affects response to tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (SpA). METHODS: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis. Participants fulfilling the Assessment of SpondyloArthritis international Society criteria for axial SpA who started their first TNFi were eligible for analysis. In comparing the impact of smoking status, weighted generalized estimating equations were used to examine changes in several continuous outcome measures, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Inverse probability weights were used to account for differences in baseline covariates and excluded participants. We separately assessed response in the first 3 months to account for nonrandom dropout. RESULTS: For 840 participants who started on TNFi, 1,641 assessments from 627 individuals were analyzed (69% male, mean age 46 years). A total of 33% were current smokers and 30% ex-smokers. Ex-smokers and current smokers had worse disease than never smokers at baseline. Accounting for these differences, response did not differ according to smoking status. Compared to never smokers, ex-smokers (ß = -0.6, 95% confidence interval [95% CI] -1.4, 0.3) and current smokers (ß = -0.4, 95% CI -1.1, 0.4) had a similar response according to the BASDAI and ASDAS (ex-smokers ß = -0.1, 95% CI -0.5, 0.3; current smokers ß = -0.01, 95% CI -0.4, 0.4) at 3 months. CONCLUSION: TNFi response did not differ according to baseline smoking status in this UK cohort. Conflicting results from previous studies were likely due to methodologic differences. This analysis highlights potential sources of bias that should be addressed in future studies.


Assuntos
Antirreumáticos/uso terapêutico , Fumar , Espondilartrite/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Resultado do Tratamento , Reino Unido
19.
J Rheumatol ; 47(8): 1261-1266, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676701

RESUMO

OBJECTIVE: Little is known about acute calcium pyrophosphate (CPP) crystal arthritis flare rates and risk factors for recurrence. We characterized flares and determined the rate and predictors of acute CPP crystal arthritis flares in an academic medical center cohort. METHODS: We performed a retrospective cohort study among a random sample of patients with acute CPP crystal arthritis identified in the Partners HealthCare electronic medical record, 1991-2017. Flare was defined as self-limited, acute-onset synovitis with synovial fluid CPP crystals and/or chondrocalcinosis, not better explained by another cause. We calculated incidence rates (IR) for acute CPP crystal arthritis flare among all subjects and by sex. We estimated HR for recurrent flare using univariate Cox models that accounted for within-person correlated data. RESULTS: We identified 70 patients with acute CPP crystal arthritis with a total of 111 flares. Recurrent flares occurred in 24% of patients; half of flares occurred in a previously unaffected joint. The acute CPP crystal arthritis flare rate was 11.4 per 100 person-years overall (95% CI 8.2-15.4), 14.2 in women (95% CI 9.6-0.1), and 7.1 in men (95% CI 3.4-13.0). Cancer (HR 2.98, 95% CI 1.33-6.68) and chronic kidney disease (HR 2.92, 95% CI 1.10-7.76) were associated with a higher rate for recurrent flare. CONCLUSION: Recurrent flares occurred in about one-fourth of patients with acute CPP crystal arthritis and often occurred in previously unaffected joints. The acute CPP crystal arthritis flare rate was twice as high in women as in men.

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