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Julia F. Simard

Bio: Julia F. Simard is an academic researcher from Stanford University. The author has contributed to research in topics: Population & Rheumatoid arthritis. The author has an hindex of 38, co-authored 121 publications receiving 4361 citations. Previous affiliations of Julia F. Simard include Harvard University & University of Manchester.


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Journal ArticleDOI
TL;DR: It is found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds ofospitalisation in patients with rheumatic disease.
Abstract: Objectives COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease. Methods Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed. Results A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed. Conclusions We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.

883 citations

Journal ArticleDOI
TL;DR: 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).
Abstract: 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.

322 citations

Journal ArticleDOI
TL;DR: This nationwide approach yielded a prevalence of RA similar to previous regional assessments, while displaying only modest geographical variation and no urban/rural gradient, prevalence was associated with educational level.
Abstract: Objective To provide Swedish nationwide data on the prevalence of rheumatoid arthritis (RA), including variations by age, sex, geography, demography and education level, and assess antirheumatic treatment penetration. Methods Patients ≥16 years assigned an RA diagnosis were identified from inpatient (n=96 560; 1964–2007) and specialist outpatient care (n=56 336; 2001–2007) in the Swedish National Patient Register, and the Swedish Rheumatology Quality Register (n=21 242; 1995–2007). Data on prescriptions, demography, vital status and educational level were retrieved from national registers. Results A total of 58 102 individuals (mean age 66 years; 73% women) assigned an RA diagnosis were alive in Sweden in 2008, corresponding to a cumulative prevalence of 0.77% (women 1.11%, men 0.43%). The 2001–2007 period prevalence was 0.70%. Restriction to patients with ≥2 visits or diagnosis from a rheumatologist/internist reduced the overall cumulative prevalence to 0.68%. Whereas urban/rural differences (crude 0.65–1.00%) were explained by age differences, the age/sex-adjusted prevalence remained higher in patients with ≤9 years education (0.86%) than for those with 10–12 years (0.82%) and >12 years (0.65%). Treatment exposures (76% any disease-modifying antirheumatic drugs (DMARDs) or steroids, 64% any DMARD, 15% biological agents) varied with age; use of biological agents decreased from 22% in 16–59 years olds to 3% in ≥80 years olds. Any DMARD use correspondingly decreased from 71% to 43%. Applying age cut-off points from previous northern European and North American prevalence studies reduced or eliminated between-study differences. Conclusion This nationwide approach yielded a prevalence of RA similar to previous regional assessments. While displaying only modest geographical variation and no urban/rural gradient, prevalence was associated with educational level. Although most patients received antirheumatic drugs, age was a strong treatment determinant.

213 citations

Journal ArticleDOI
08 Apr 2013-BMJ
TL;DR: Overall, patients with rheumatoid arthritis who have not been treated with biological drugs are not at increased risk of invasive melanoma compared with the general population, and may not markedly shift the overall risk-benefit balance of TNF inhibitors as used in clinical practice.
Abstract: Objectives To investigate the potential association between tumour necrosis factor (TNF) inhibitor treatment and malignant melanomas in rheumatoid arthritis, melanoma risks in rheumatoid arthritis patients not treated with biological drugs, and risk of all site cancer with TNF inhibitors as used in rheumatoid arthritis. Design Population based cohort study. Setting Prospectively recorded data from national clinical, health, and demographic registers in Sweden 2001-10. Patients with rheumatoid arthritis treated (n=10 878) or not (n=42 198) with TNF inhibitors and matched general population comparators (n=162 743). Main outcome measures The primary outcome was first invasive melanoma in people without any history of invasive cancer of any type. Hazard ratios were estimated using Cox regression, comparing non-biological drug treated rheumatoid arthritis patients with the general population comparator and TNF inhibitor treated rheumatoid arthritis patients with those not treated with biological drugs. Secondary outcomes included in situ melanomas, second primary melanomas, and all site cancer. Results 113 first invasive melanomas occurred in rheumatoid arthritis patients not treated with biological drugs, and 393 occurred in the general population comparator cohort. Rheumatoid arthritis patients not treated with biological drugs were not at significantly increased risk of melanoma compared with the general population (hazard ratio 1.2, 95% confidence interval 0.9 to 1.5). 38 first invasive melanomas occurred in rheumatoid arthritis patients treated with TNF inhibitors; these patients had an increased risk of melanoma compared with rheumatoid arthritis patients not treated with biological drugs (hazard ratio 1.5, 1.0 to 2.2; 20 additional cases per 100 000 person years). The risk of a second primary melanoma was non-significantly increased (hazard ratio 3.2, 0.8 to 13.1; n=3 v 10) in rheumatoid arthritis patients treated with TNF inhibitors compared with those not treated with biological drugs. Conclusion Overall, patients with rheumatoid arthritis who have not been treated with biological drugs are not at increased risk of invasive melanoma compared with the general population. Rheumatoid arthritis patients selected for TNF inhibitor treatment are not at increased overall risk for cancer but have a 50% increased relative risk of invasive melanoma. Given the small increase in absolute risk, these finding may not markedly shift the overall risk-benefit balance of TNF inhibitors as used in clinical practice but might do so in patients at high risk of melanoma for other reasons.

192 citations

Journal ArticleDOI
TL;DR: In this population of rheumatoid arthritis patients, infliximab was associated with a higher risk of requiring intensification of DMARD co-therapy than the other anti-TNF agents and a significant dose escalation over time.
Abstract: Background: Acquired drug resistance or gradual drug failure has been described with most disease modifying antirheumatic drugs (DMARDs) and is also starting to be recognised with anti-tumour necrosis factor (anti-TNF) agents. Objective: To study acquired drug resistance to anti-TNF agents in rheumatoid arthritis (RA). Methods: Swiss health authorities requested continuous monitoring of patients receiving biological agents. Intensification of co-therapy with traditional DMARDs, gradual dose escalation, and drug discontinuation rates in all patients receiving infliximab, etanercept, or adalimumab, adjusting for potential confounders, were analysed. Intensification of DMARD co-therapy and time to discontinuation of the three anti-TNF agents were analysed using a proportional hazards models. Dose escalation and evolution of RA disease activity (DAS28) were analysed using a longitudinal regression model. Results: 1198 patients contributing 1450 patient-years of anti-TNF treatment met the inclusion criteria. The rate of intensification of traditional DMARD co-therapy over time was significantly higher with infliximab (hazards ratio = 1.73 (99% confidence interval (CI) 1.19 to 2.51)) than with the two other agents. Infliximab also showed significant dose escalation over time, with an average dose increase of +12% (99% CI 8% to 16%) after 1 year, and +18% (99% CI 11% to 25%) after 2 years. No significant differences in discontinuation rates were seen between the three anti-TNF agents (ANOVA, p = 0.67). Evolution of disease activity over time indicated a lower therapeutic response to infliximab (DAS28, p Conclusions: In this population, infliximab was associated with a higher risk of requiring intensification of DMARD co-therapy than the other anti-TNF agents and a significant dose escalation over time. Analysis of RA disease activity indicated a reduced therapeutic response to infliximab after the first 6 months of treatment, suggestive of acquired drug resistance.

164 citations


Cited by
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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA), a large number of patients with RA are referred to a single clinic for treatment with these medications.
Abstract: Objective To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). Methods We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. Results The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. Conclusion This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

2,083 citations

Journal ArticleDOI
TL;DR: The relationship between diet, microbial metabolism and CRC is discussed and it is argued that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.
Abstract: Accumulating evidence suggests that the human intestinal microbiota contributes to the aetiology of colorectal cancer (CRC), not only via the pro-carcinogenic activities of specific pathogens but also via the influence of the wider microbial community, particularly its metabolome. Recent data have shown that the short-chain fatty acids acetate, propionate and butyrate function in the suppression of inflammation and cancer, whereas other microbial metabolites, such as secondary bile acids, promote carcinogenesis. In this Review, we discuss the relationship between diet, microbial metabolism and CRC and argue that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.

1,866 citations

Journal ArticleDOI
TL;DR: The biology of T NF and related family members are discussed in the context of the potential mechanisms of action of TNF antagonists in a variety of immune-mediated inflammatory diseases.

1,517 citations

Journal ArticleDOI
TL;DR: The 2012 ACR RA recommendations were developed by two expert panels: a non-voting working group and Core Expert Panel of clinicians and methodologists responsible for the selection of the relevant topic areas to be considered, the systematic literature review, and the evidence synthesis.
Abstract: The American College of Rheumatology (ACR) most recently published recommendations for use of disease modifying anti-rheumatic drugs (DMARDs) and biologics in the treatment of rheumatoid arthritis (RA) in 2008 (1). These recommendations covered indications for use, monitoring of side-effects, assessment of the clinical response to DMARDs and biologics, screening for tuberculosis (TB), and assessment of the roles of cost and patient preference in decision-making for biologic agents (1). Recognizing the rapidly evolving knowledge in RA management and the accumulation of new evidence regarding the safety and efficacy of existing and newer therapies, the ACR commissioned an update of the 2008 recommendations in select topic areas. The 2012 revision updates the 2008 ACR recommendations in the following areas: (1) indications for DMARDs and biologics; (2) switching between DMARD and biologic therapies; (3) use of biologics in high-risk patients (those with hepatitis, congestive heart failure, and malignancy); (4) screening for TB in patients starting or currently receiving biologics; and (5) vaccination in patients starting or currently receiving DMARDs or biologics (Table 1). Table 1 Overview Comparison of Topics and Medications Included in the 2008 and 2012 ACR RA Recommendations METHODS We utilized the same methodology as described in detail in the 2008 guidelines (1) to maintain consistency and to allow cumulative evidence to inform this 2012 recommendation update. These recommendations were developed by two expert panels: (1) a non-voting working group and Core Expert Panel (CEP) of clinicians and methodologists responsible for the selection of the relevant topic areas to be considered, the systematic literature review, and the evidence synthesis and creation of “clinical scenarios”; and (2) a Task Force Panel (TFP) of 11 internationally-recognized expert clinicians, patient representatives and methodologists with expertise in RA treatment, evidence-based medicine and patient preferences who were tasked with rating the scenarios created using an ordinal scale specified in the Research and Development/University of California at Los Angeles (RAND/UCLA) Appropriateness method (2–4). This method solicited formal input from a multi-disciplinary TFP panel to make recommendations informed by the evidence. The methods used to develop the updated ACR recommendations are described briefly below. Systematic Literature Review – Sources, Databases and Domains Literature searches for both DMARDs and biologics relied predominantly on PubMed searches) with medical subject headings (MeSH) and relevant keywords similar to those used for the 2008 ACR RA recommendations (see Appendices 1 and 2). We included randomized clinical trials (RCTs), controlled clinical trials (CCTs), quasi-experimental designs, cohort studies (prospective or retrospective), and case-control studies, with no restrictions on sample size. More details about inclusion criteria are listed below and in Appendix 3. The 2008 recommendations were based on a literature search that ended on February 14, 2007. The literature search end date for the 2012 Update was February 26, 2010 for the efficacy and safety studies and September 22, 2010 for additional qualitative reviews related to TB screening, immunization and hepatitis (similar to the 2008 methodology). Studies published subsequent to that date were not included. For biologics, we also reviewed the Cochrane systematic reviews and overviews (published and in press) in the Cochrane Database of Systematic Reviews to identify additional studies (5–8) and further supplemented by hand-checking the bibliographies of all included articles. Finally, the CEP and TFP confirmed that relevant literature was included for evidence synthesis. Unless they were identified by the literature search and met the article inclusion criteria (see Appendix 3), we did not review any unpublished data from product manufacturers, investigators, or the Food and Drug Administration (FDA) Adverse Event Reporting System. We searched the literature for the eight DMARDs and nine biologics most commonly used for the treatment of RA. Literature was searched for eight DMARDS including azathioprine, cyclosporine, hydroxychloroquine, leflunomide, methotrexate, minocycline, organic gold compounds and sulfasalazine. As in 2008, azathioprine, cyclosporine and gold were not included in the recommendations based on infrequent use and lack of new data (Table 1). Literature was searched for nine biologics including abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab; anakinra was not included in the recommendations due to infrequent use and lack of new data. Details of the bibliographic search strategy are listed in Appendix 1.

1,493 citations