Publications by authors named "Sara K Tedeschi"

69 Publications

Identifying potential classification criteria for calcium pyrophosphate deposition disease (CPPD): Item generation and item reduction.

Arthritis Care Res (Hoboken) 2021 May 10. Epub 2021 May 10.

Division of Rheumatology, University of Alabama at Birmingham, Birmingham Veterans Affairs Medical Center, Birmingham, United States.

Objective: Classification criteria for calcium pyrophosphate deposition disease (CPPD) will facilitate clinical research on this common crystalline arthritis. We report on the first two phases of a four-phase process for developing CPPD classification criteria.

Methods: CPPD classification criteria development is overseen by a 12-member Steering Committee. Item generation (Phase I) included a scoping literature review of five literature databases and contributions from a 35-member Combined Expert Committee and two Patient Research Partners. Item reduction and refinement (Phase II) involved a Combined Expert Committee meeting, discussions among Clinical, Imaging, and Laboratory Advisory Groups, and an item rating exercise to assess the influence of individual items toward classification. The Steering Committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development.

Results: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The Advisory Groups eliminated items they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the Steering Committee recommended focusing on imaging of the knee, wrist, and one additional affected joint for calcification suggestive of CPP crystal deposition.

Conclusion: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.
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http://dx.doi.org/10.1002/acr.24619DOI Listing
May 2021

Experience and impact of crystal pyrophosphate deposition (CPPD) from a patient and caregiver perspective: A qualitative exploration from the OMERACT CPPD working group.

Semin Arthritis Rheum 2021 Jun 21;51(3):655-660. Epub 2021 Apr 21.

Academic Rheumatology, University of Nottingham, Nottingham, UK; NIHR Nottingham Biomedical Research Centre, Nottingham, UK.

Objective: To explore the lived experience of people with calcium pyrophosphate deposition (CPPD) disease and the impact of this condition on their daily lives.

Methods: Patients with CPPD and their caregivers were invited to take part in a one-to-one (patient only) or paired (patient and caregiver) semi-structured interview. Interviews covered patients' diagnosis and treatment experiences, and the impact of CPPD on their daily lives. Transcribed interviews were analysed using inductive thematic analysis.

Results: 28 patient interviews, six of which included a caregiver, were conducted across five countries. Acute CPP crystal arthritis flares resulted in temporary but profound disability for most patients, disrupting their ability to go about day-to-day activities, and they sought immediate medical attention. CPPD+OA and chronic CPP crystal inflammatory arthritis presented patients with longer term limitations in daily lives. Patients and their caregivers described these disruptions and limitations, which included a reduced ability or inability to complete household and self-care tasks, exercise, socialise, work and drive. They also described how arthritis pain and resulting limitations adversely impacted upon patients' psychological wellbeing. Delays in referral to specialists and diagnostic uncertainty were described by many. Lack of appropriate treatment or access to treatments only upon worsening of symptoms impacted upon the length of time some patients spent in pain and with functional limitations.

Conclusion: This study is the first to demonstrate the wide-ranging impact of CPPD, and highlights the need for improved diagnosis, physician training, as well as greater emphasis upon finding targeted therapies to specifically treat CPPD.
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http://dx.doi.org/10.1016/j.semarthrit.2021.04.010DOI Listing
June 2021

Clinical Experience With a Multidisciplinary Model of Vascular Ultrasound for the Evaluation for Giant Cell Arteritis.

ACR Open Rheumatol 2021 Mar 11;3(3):147-153. Epub 2021 Feb 11.

Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts.

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.
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http://dx.doi.org/10.1002/acr2.11227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966877PMC
March 2021

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance.

Ann Rheum Dis 2021 Feb 10. Epub 2021 Feb 10.

Department of Medicine, Division of Rheumatology, University of California at San Francisco and the VA Medical Center, San Francisco, California, USA.

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.
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http://dx.doi.org/10.1136/annrheumdis-2020-219373DOI Listing
February 2021

Identification of Acute Giant Cell Arteritis in Real-World Data Using Administrative Claims-Based Algorithms.

ACR Open Rheumatol 2021 Feb 25;3(2):72-78. Epub 2021 Jan 25.

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

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.
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http://dx.doi.org/10.1002/acr2.11218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882520PMC
February 2021

Outcome domains reported by patients, caregivers, healthcare professionals and stakeholders for calcium pyrophosphate deposition (CPPD): A content analysis based on semi-structured qualitative interviews from the OMERACT CPPD working group.

Semin Arthritis Rheum 2021 Jun 6;51(3):650-654. Epub 2021 Jan 6.

Academic Rheumatology, University of Nottingham, Nottingham, UK; NIHR Nottingham Biomedical Research Centre, Nottingham, UK.

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.
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http://dx.doi.org/10.1016/j.semarthrit.2020.09.021DOI Listing
June 2021

Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities.

Ann Rheum Dis 2020 10 14;79(10):1333-1339. Epub 2020 Aug 14.

Rheumatology, Azienda Ospedaliero Universitaria Pisana, Pisa, Toscana, Italy.

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.
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http://dx.doi.org/10.1136/annrheumdis-2020-217162DOI Listing
October 2020

Delayed Denosumab Injections and Fracture Risk Among Patients With Osteoporosis : A Population-Based Cohort Study.

Ann Intern Med 2020 10 28;173(7):516-526. Epub 2020 Jul 28.

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (D.H.S.).

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) ( 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.
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http://dx.doi.org/10.7326/M20-0882DOI Listing
October 2020

Abdominal Obesity in Comparison with General Obesity and Risk of Developing Rheumatoid Arthritis in Women.

J Rheumatol 2021 02 15;48(2):165-173. Epub 2020 Jul 15.

N.E. Marchand, ScD, J.A. Sparks, MD, MMSc, S.K. Tedeschi, MD, MPH, S. Malspeis, K.H. Costenbader, MD, MPH, E.W. Karlson, MD, B. Lu, MD, DrPH, Division of Rheumatology, Inflammation and Immunity, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

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 (HR 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.
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http://dx.doi.org/10.3899/jrheum.200056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006183PMC
February 2021

Follow-up vascular ultrasounds in patients with giant cell arteritis.

Clin Exp Rheumatol 2020 Mar-Apr;38 Suppl 124(2):107-111. Epub 2020 Apr 27.

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Boston, and Harvard Medical School, Boston, MA, USA.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812681PMC
September 2020

Circulating plasma metabolites and risk of rheumatoid arthritis in the Nurses' Health Study.

Rheumatology (Oxford) 2020 11;59(11):3369-3379

Section of Clinical Sciences, Division of Rheumatology, Brigham and Women's Hospital.

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.
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http://dx.doi.org/10.1093/rheumatology/keaa125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590418PMC
November 2020

Achievement of remission in two early rheumatoid arthritis cohorts implementing different treat-to-target strategies.

Arthritis Rheumatol 2020 Feb 23. Epub 2020 Feb 23.

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

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.
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http://dx.doi.org/10.1002/art.41232DOI Listing
February 2020

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

Arthritis Rheumatol 2020 04 23;72(4):529-556. Epub 2020 Feb 23.

American College of Rheumatology, Atlanta, Georgia.

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.
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http://dx.doi.org/10.1002/art.41191DOI Listing
April 2020

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

Arthritis Care Res (Hoboken) 2020 04 26;72(4):461-488. Epub 2020 Feb 26.

American College of Rheumatology, Atlanta, Georgia.

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.
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http://dx.doi.org/10.1002/acr.24130DOI Listing
April 2020

Adverse Effects of Low-Dose Methotrexate: A Randomized Trial.

Ann Intern Med 2020 03 18;172(6):369-380. Epub 2020 Feb 18.

Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.).

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.
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http://dx.doi.org/10.7326/M19-3369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229518PMC
March 2020

Classifying Pseudogout Using Machine Learning Approaches With Electronic Health Record Data.

Arthritis Care Res (Hoboken) 2021 03;73(3):442-448

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Objective: Identifying pseudogout in large data sets is difficult due to its episodic nature and a lack of billing codes specific to this acute subtype of calcium pyrophosphate (CPP) deposition disease. The objective of this study was to evaluate 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 subjects for gold standard chart review for definite pseudogout (synovitis + synovial fluid CPP crystals), probable pseudogout (synovitis + chondrocalcinosis), or 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 billing codes, the presence of CPP crystals, topic modeling, and a combined algorithm.

Results: Among 900 subjects, 123 (13.7%) had pseudogout by chart review (68 definite, 55 probable). Billing codes had a sensitivity of 65% and a positive predictive value (PPV) of 22% for pseudogout. The presence of CPP crystals had a sensitivity of 29% and a PPV of 92%. Without using CPP crystal results, topic modeling had a sensitivity of 29% and a PPV of 79%. The combined algorithm yielded a sensitivity of 42% and a PPV of 81%. The combined algorithm identified 50% more patients than the 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 laboratory results yielded an algorithm that significantly boosted the PPV compared to billing codes.
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http://dx.doi.org/10.1002/acr.24132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338229PMC
March 2021

Delayed Denosumab Injections and Bone Mineral Density Response: An Electronic Health Record-based Study.

J Clin Endocrinol Metab 2020 05;105(5)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, Massachusetts, USA.

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.
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http://dx.doi.org/10.1210/clinem/dgz321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089847PMC
May 2020

Roles of Postdiagnosis Accumulation of Morbidities and Lifestyle Changes in Excess Total and Cause-Specific Mortality Risk in Rheumatoid Arthritis.

Arthritis Care Res (Hoboken) 2021 02;73(2):188-198

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Objective: To elucidate how postdiagnosis multimorbidity and lifestyle changes contribute to the excess mortality of rheumatoid arthritis (RA).

Methods: We performed a matched cohort study among women in the Nurses' Health Study (1976-2018). We identified women with incident RA and matched each by age and year to 10 non-RA comparators at the RA diagnosis index date. Specific causes of death were ascertained via death certificates and medical record review. Lifestyle and morbidity factors were reported biennially; 61 chronic conditions were combined into the Multimorbidity Weighted Index (MWI). After adjusting for baseline confounders, we used inverse probability weighting analysis to examine the mediating influence of postindex MWI scores and lifestyle factors on total, cardiovascular, and respiratory mortality, comparing women with RA to their matched comparators.

Results: We identified 1,007 patients with incident RA and matched them to 10,070 non-RA comparators. After adjusting for preindex confounders, we found that hazard ratios (HRs) and 95% confidence intervals (95% CIs) were higher for total mortality (HR 1.46 [95% CI 1.32, 1.62]), as well as cardiovascular (HR 1.54 [95% CI 1.22, 1.94]) and respiratory (HR 2.75 [95% CI 2.05, 3.71]) mortality in patients with RA compared to non-RA comparators. Adjusting for postindex lifestyle factors (physical activity, body mass index, diet, smoking) attenuated but did not substantially account for this excess RA mortality. After additional adjustment for postindex MWI scores, patients with RA had HRs of 1.18 (95% CI 1.05, 1.32) for total, 1.19 (95% CI 0.94, 1.51) for cardiovascular, and 1.93 (95% CI 1.42, 2.62) for respiratory mortality.

Conclusion: We found that MWI scores substantially accounted for the excess total and cardiovascular mortality among women with RA. This finding underscores the importance of monitoring for the total disease burden as a whole in monitoring patients with RA.
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http://dx.doi.org/10.1002/acr.24120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275877PMC
February 2021

Acute Calcium Pyrophosphate Crystal Arthritis Flare Rate and Risk Factors for Recurrence.

J Rheumatol 2020 08 1;47(8):1261-1266. Epub 2019 Nov 1.

From the Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

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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http://dx.doi.org/10.3899/jrheum.190778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192778PMC
August 2020

Effect of vitamin D on serum markers of bone turnover in SLE in a randomised controlled trial.

Lupus Sci Med 2019 17;6(1):e000352. Epub 2019 Sep 17.

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objective: Bone health in SLE is adversely affected by vitamin D deficiency, inflammatory cytokines and glucocorticoid use. We hypothesised that vitamin D supplementation would increase markers of bone formation and decrease markers of bone resorption in SLE subjects.

Methods: We studied 43 vitamin D-deficient SLE subjects who participated in a 12-week randomised controlled trial of 2000-4000 IU/day vitamin D supplementation versus placebo. Subjects had inactive SLE (SLE Disease Activity Index ≤4) and were taking <20 mg prednisone daily at baseline. We assayed baseline and week 12 serum 25-hydroxyvitamin D, N-terminal propeptide of type 1 collagen (P1NP) and C-telopeptide (CTX). We tested the effect of vitamin D versus placebo on change (Δ) in P1NP and ΔCTX in an intention-to-treat analysis. Secondary analyses evaluated whether vitamin D affected bone turnover among subjects achieving vitamin D repletion (≥30 ng/mL) or currently taking glucocorticoids.

Results: 28 subjects were randomised to vitamin D and 15 to placebo. Mean age was 39 years and 40% were using glucocorticoids at enrolment. Repletion was achieved by 46% in the vitamin D group versus none in the placebo group. Changes in bone turnover markers were not significantly different in the vitamin D group versus placebo group (median ΔP1NP -0.2 vitamin D group vs -1.1 placebo group (p=0.83); median ΔCTX +3.5 vitamin D group vs -37.0 placebo group (p=0.50)). The effect of vitamin D did not differ based on achieving vitamin D repletion or baseline glucocorticoid use.

Conclusion: Vitamin D supplementation did not affect the 12-week change in bone turnover markers among SLE subjects in this trial.
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http://dx.doi.org/10.1136/lupus-2019-000352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762038PMC
September 2019

Associations Between Classification Criteria Items in Systemic Lupus Erythematosus.

Arthritis Care Res (Hoboken) 2020 12 7;72(12):1820-1826. Epub 2020 Nov 7.

University of Pisa, Pisa, Italy.

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.
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http://dx.doi.org/10.1002/acr.24078DOI Listing
December 2020

Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout.

Ann Rheum Dis 2019 11 9;78(11):1592-1600. Epub 2019 Sep 9.

Department of Rheumatology, Hôpital Lariboisière, Paris, France.

Objective: There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout.

Methods: A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions.

Results: The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus).

Conclusion: Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.
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http://dx.doi.org/10.1136/annrheumdis-2019-215933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288724PMC
November 2019

2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus.

Arthritis Rheumatol 2019 09 6;71(9):1400-1412. Epub 2019 Aug 6.

Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.

Objective: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).

Methods: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects.

Results: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.

Conclusion: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.
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http://dx.doi.org/10.1002/art.40930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827566PMC
September 2019

2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus.

Ann Rheum Dis 2019 09 5;78(9):1151-1159. Epub 2019 Aug 5.

Department of Clinical and Experimental Medicine, Rheumatology Unit, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.

Objective: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).

Methods: This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects.

Results: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.

Conclusion: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
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http://dx.doi.org/10.1136/annrheumdis-2018-214819DOI Listing
September 2019

Issues in CPPD Nomenclature and Classification.

Authors:
Sara K Tedeschi

Curr Rheumatol Rep 2019 07 25;21(9):49. Epub 2019 Jul 25.

Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA, 02115, USA.

Purpose Of Review: This paper covers confusion and challenges in the nomenclature of calcium pyrophosphate deposition disease. Clinicians, investigators, and patients are faced with a variety of terms that are used to describe CPPD and its phenotypes, and clarity is greatly needed to help advance research and patient care. Motivation for the upcoming development of CPPD classification criteria is reviewed.

Recent Findings: EULAR proposed recommended terminology for CPPD in 2011. International Classification of Diseases (ICD-9 and ICD-10) billing codes identify definite or probable CPPD with variable accuracy depending on the clinical setting and comparator group. READ diagnostic codes have been employed to identify pseudogout in UK datasets but their accuracy has not been evaluated. CPPD classification criteria will provide a system for identifying a relatively homogenous group of patients to be included in clinical studies, enabling comparison of outcomes across studies. CPPD nomenclature remains challenging for clinicians, investigators, and patients. A lay-friendly definition of CPPD, using easily accessible terminology, would be welcome. CPPD classification criteria are a necessary step in moving forward CPPD clinical research and may involve a range of clinical, laboratory, and imaging modalities.
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http://dx.doi.org/10.1007/s11926-019-0847-4DOI Listing
July 2019

Smoking status and cause-specific discontinuation of tumour necrosis factor inhibitors in axial spondyloarthritis.

Arthritis Res Ther 2019 07 22;21(1):177. Epub 2019 Jul 22.

Musculoskeletal Biology I, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Background: The impact of smoking on TNF inhibition (TNFi) therapy is unclear. We examined the effect of smoking on all-cause and cause-specific TNFi discontinuation in axial spondyloarthritis (axSpA).

Methods: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS). Patients fulfilling the ASAS criteria for axSpA, who started their first TNFi, were eligible for analysis. Inverse-probability weights were used to balance differences in baseline disease severity and other confounders. We used marginal structural Cox proportional hazard models to estimate hazard ratios (HR) for TNFi discontinuation according to smoking status. In analyses of cause-specific discontinuation, competing risk events were considered as censoring, using inverse-probability weights.

Results: A total of 758 participants were included in the analysis (66% male, mean age 45 years), providing 954 patient-years of follow-up. TNFi was discontinued in 174 (23%) patients, among whom 26% stopped due to infections, 20% due to other adverse events and 44% due to inefficacy or other reasons. Thirty-four percent were current smokers and 30% ex-smokers. Compared to never smokers, current smokers' risk of TNFi discontinuation was HR 0.79 (95%CI 0.53 to 1.20) and ex-smokers HR 0.68 (95%CI 0.45 to 1.04). Our data did not show evidence that current smoking influenced discontinuation due to infections (HR 0.79, 95%CI 0.40 to 1.54), other adverse events (HR 0.86, 95%CI 0.41 to 1.78) or inefficacy/other causes (HR 1.44, 95%CI 0.86 to 2.41).

Conclusion: Baseline smoking status did not impact TNFi discontinuation in this UK cohort of axSpA participants.
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http://dx.doi.org/10.1186/s13075-019-1958-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647300PMC
July 2019

Comparison of Teriparatide and Denosumab in Patients Switching From Long-Term Bisphosphonate Use.

J Clin Endocrinol Metab 2019 11;104(11):5611-5620

Division of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts.

Context: Teriparatide and denosumab are effective treatments for osteoporosis and typically reserved as second-line options after patients have used bisphosphonates. However, limited head-to-head comparative effectiveness data exist between teriparatide and denosumab.

Objective: We compared changes in bone mineral density (BMD) between groups treated with teriparatide or denosumab after using bisphosphonates, focusing on the change in BMD while on either drug over 2 years.

Design: Observational cohort study using electronic medical records from two academic medical centers in the United States.

Participants: The study population included osteoporotic patients >45 years who received bisphosphonates >1 year before switching to teriparatide or denosumab.

Outcome Measures: Annualized BMD change from baseline at the lumbar spine, total hip, and femoral neck.

Results: Patients treated with teriparatide (n = 110) were compared with those treated with denosumab (n = 105); the mean (SD) age was 70 (10) years and median duration (interquartile range) of bisphosphonate use was 7.0 (5.6 to 9.7) years. Compared with denosumab users, teriparatide users had higher annualized BMD change at the spine by 1.3% (95% CI 0.02, 2.7%) but lower at the total hip by -2.2% (95% CI -2.9 to -1.5%) and the femoral neck by -1.1% (95% CI -2.1 to -0.1%). Those who switched to teriparatide had a transient loss of hip BMD for the first year, with no overall increase in the total hip BMD over 2 years.

Conclusions: Among patients who use long-term bisphosphonates, the decision of switching to teriparatide should be made with caution, especially for patients at high risk of hip fracture.
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http://dx.doi.org/10.1210/jc.2019-00924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785688PMC
November 2019

A tool for empirical equipoise assessment in multigroup comparative effectiveness research.

Pharmacoepidemiol Drug Saf 2019 07 27;28(7):934-941. Epub 2019 May 27.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Purpose: In observational research, equipoise concerns whether groups being compared are similar enough for valid inference. Empirical equipoise was previously proposed as a tool to assess patient similarity based on propensity scores (PS). We extended this work for multigroup observational studies.

Methods: We modified the tool to allow for multinomial exposures such that the proposed definition reduces to the original when there are only two groups. We illustrated how the tool can be used as a method to assess study design within three-group clinical examples. We then conducted three-group simulations to assess how the tool performed in a setting with residual confounding after PS weighting.

Results: In a clinical example based on rheumatoid arthritis, 44.5% of the sample fell within the region of empirical equipoise when considering first-line biologics, whereas 57.7% did so for second-line biologics, consistent with the expectation that a second-line design results in better equipoise. In a simulation where the unmeasured confounder had the same magnitude of association with the treatment as the measured confounders and a 25% greater association with the outcome, the tool crossed the proposed threshold for empirical equipoise at a residual confounding of 20% on the ratio scale. When the unmeasured variable had a twice larger association with treatment, the tool became less sensitive and crossed the threshold at a residual confounding of 30%.

Conclusion: Our proposed tool may be useful in guiding cohort identification in multigroup observational studies, particularly with similar effects of unmeasured and measured covariates on treatment and outcome.
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http://dx.doi.org/10.1002/pds.4767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057252PMC
July 2019

Comparison of comorbidities and treatment between ankylosing spondylitis and non-radiographic axial spondyloarthritis in the United States.

Rheumatology (Oxford) 2019 11;58(11):2025-2030

Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA.

Objectives: This study aimed to compare comorbidities and biologic DMARD (bDMARD) use between AS and non-radiographic axial SpA (nr-axSpA) patients, using a large cohort of patients from routine clinical practice in the United States.

Methods: We performed a cross-sectional study using electronic medical records from two academic hospitals in the United States. Data were extracted using automated searches (⩾3 ICD codes combined with text searches) and supplemented with manual chart review. Patients were categorized into AS or nr-axSpA according to classification criteria. Disease features, comorbidities (from a list of 39 chronic conditions) and history of bDMARD prescription were compared using descriptive statistics.

Results: Among 965 patients identified, 775 (80%) were classified as having axSpA. The cohort was predominantly male (74%) with a mean age of 52.5 years (s.d. 16.8). AS patients were significantly older (54 vs 46 years), more frequently male (77% vs 64%) and had higher serum inflammatory markers than those with nr-axSpA (median CRP 3.4 vs 2.2 mg/dl). Half of all patients had at least one comorbidity. The mean number of comorbidities was 1.5 (s.d. 2.2) and similar between AS and nr-axSpA groups. A history of bDMARD-use was seen in 55% of patients with no difference between groups. The most commonly prescribed bDMARDs were adalimumab (31%) and etanercept (29%). Ever-prescriptions of individual bDMARDs were similar between AS and nr-axSpA.

Conclusion: Despite age differences, nr-axSpA patients had similar comorbidity burdens as those with AS. Both groups received comparable bDMARD treatment in this United States clinic-based cohort.
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http://dx.doi.org/10.1093/rheumatology/kez171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967894PMC
November 2019