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BACKGROUND: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. OBJECTIVE: To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. DESIGN: Retrospective matched cohort analysis. SETTING: Academic medical center/pituitary center. PATIENTS: Patients with CD with surgical remission and surgically treated NFPA. MEASUREMENTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. RESULTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). LIMITATION: The small sample of patients with autoimmune disease limited identification of independent risk factors. CONCLUSION: Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. PRIMARY FUNDING SOURCE: Recordati Rare Diseases Inc.
Subject(s)
Adrenal Insufficiency , Autoimmune Diseases , Pituitary ACTH Hypersecretion , Pituitary Neoplasms , Humans , Cohort Studies , Hydrocortisone , Retrospective Studies , Pituitary ACTH Hypersecretion/complications , Pituitary ACTH Hypersecretion/surgery , Pituitary Neoplasms/complications , Pituitary Neoplasms/surgery , Adrenal Insufficiency/complications , Autoimmune Diseases/complicationsABSTRACT
Introduction: In this study, we investigated the prevalence of depression, depression treatment, and symptom burden in patients with systemic sclerosis (SSc) and examined their associations with the center for epidemiologic studies depression scale revised (CESD-R) scores. Methods: The Prospective Registry in Scleroderma at Massachusetts General Hospital (PRISM) is a longitudinal registry of patients with SSc. Among participants with CESD-R score ≥ 16, indicating possible depression, a chart review was performed for mental health diagnoses and treatments. We examined the relation of demographic and clinical factors to the presence of mental health diagnoses or treatment using logistic regression. We evaluated the association of SSc symptoms and the COVID-19 pandemic with a CESD-R score using quantile regression. Results: Of 214 patients enrolled in PRISM, 129 participants (38% diffuse and 59% limited) completed at least one CESD-R questionnaire. In the first survey, 29% had possible depression (CESD - R ≥ 16) and 16% had probable depression (CESD - R ≥ 23). Of 20 participants with probable depression, 90% received treatment for a mood disorder. In a multivariable logistic regression model among participants with CESD - R ≥ 16, none of the evaluated variables (CESD-R score, age, gender, employment status, race, and ethnicity) was associated with mental health diagnosis or treatment. Higher baseline dyspnea index, modified Rodnan skin score, and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal total score and subscores were associated with higher CESD-R score. Conclusion: In this single-center cross-sectional study, 16% of participants had significant depressive symptoms. Dyspnea, extent of skin involvement, and gastrointestinal symptoms were associated with depression symptoms.
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Background: The use of immune checkpoint inhibitors (ICI) is associated with cardiovascular (CV) events, and patients with pre-existing autoimmune disease are at increased CV risk. Objectives: The aim of this study was to characterize the risk for CV events in patients with pre-existing autoimmune disease post-ICI. Methods: This was a retrospective study of 6,683 patients treated with ICIs within an academic network. Autoimmune disease prior to ICI was confirmed by chart review. Baseline characteristics and risk for CV and non-CV immune-related adverse events were compared with a matched control group (1:1 ratio) of ICI patients without autoimmune disease. Matching was based on age, sex, history of coronary artery disease, history of heart failure, and diabetes mellitus. CV events were a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, or myocarditis. Univariable and multivariable Cox proportional hazards models were used to determine the association between autoimmune disease and CV events. Results: Among 502 patients treated with ICIs, 251 patients with and 251 patients without autoimmune disease were studied. During a median follow-up period of 205 days, there were 45 CV events among patients with autoimmune disease and 22 CV events among control subjects (adjusted HR: 1.77; 95% CI: 1.04-3.03; P = 0.0364). Of the non-CV immune-related adverse events, there were increased rates of psoriasis (11.2% vs 0.4%; P < 0.001) and colitis (24.3% vs 16.7%; P = 0.045) in patients with autoimmune disease. Conclusions: Patients with autoimmune disease have an increased risk for CV and non-CV events post-ICI.
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BACKGROUND: In 2017, Massachusetts General Hospital implemented the Severe Immunotherapy Complications (SIC) Service, a multidisciplinary care team for patients hospitalized with immune-related adverse events (irAEs), a unique spectrum of toxicities associated with immune checkpoint inhibitors (ICIs). This study's objectives were to evaluate the intervention's (1) effect on patient outcomes and healthcare utilization, and (2) ability to collect biological samples via a central infrastructure, in order to study the mechanisms responsible for irAEs. METHODS: A hospital database was used to identify patients who received ICIs for a malignancy and were hospitalized with severe irAEs, before (April 2, 2016-October 3, 2017) and after (October 3, 2017-October 24, 2018) SIC Service initiation. The primary outcome was readmission rate after index hospitalization. Secondary outcomes included length of stay (LOS) for admissions, corticosteroid and non-steroidal second-line immunosuppression use, ICI discontinuation, and inpatient mortality. RESULTS: In the pre-SIC period, 127 of 1169 patients treated with ICIs were hospitalized for irAEs; in the post-SIC period, 122 of 1159. After SIC service initiation, reductions were observed in irAE readmission rate (14.8% post-SIC vs 25.9% pre-SIC; OR 0.46; 95% CI 0.22 to 0.95; p=0.036) and readmission LOS (median 6 days post-SIC vs 7 days pre-SIC; 95% CI -16.03 to -0.14; p=0.046). No significant pre-initiation and post-initiation differences were detected in corticosteroid use, second-line immunosuppression, ICI discontinuation, or inpatient mortality rates. The SIC Service collected 789 blood and tissue samples from 234 patients with suspected irAEs. CONCLUSIONS: This is the first study to report that establishing a highly subspecialized care team focused on irAEs is associated with improved patient outcomes and reduced healthcare utilization. Furthermore, the SIC Service successfully integrated blood and tissue collection safety into routine care.
Subject(s)
Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/adverse effects , Immunotherapy/methods , Neoplasms/drug therapy , Translational Science, Biomedical/methods , Female , Humans , Immune Checkpoint Inhibitors/pharmacology , Male , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: The aim of this study was to characterize severe immune-related adverse events (irAEs) seen among hospitalized patients and to examine risk factors for irAE admissions and clinically relevant outcomes, including length of stay, immune checkpoint inhibitor (ICI) discontinuation, readmission, and death. METHODS: Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any ICI combination) at Massachusetts General Hospital (MGH) and were hospitalized at MGH following ICI initiation between January 1, 2011, and October 24, 2018, were identified using pharmacy and hospital admission databases. Medical records of all irAE admissions were reviewed, and specialist review with defined criteria was performed. Demographic data, relevant clinical history (malignancy type and most recent ICI regimen), and key admission characteristics, including dates of admission and discharge, immunosuppressive management, ICI discontinuation, readmission, and death, were collected. RESULTS: In total, 450 admissions were classified as irAE admissions and represent the study's cohort. Alongside the increasing use of ICIs at our institution, the number of patients admitted to MGH for irAEs has gradually increased every year from 9 in 2011 to 92 in 2018. The hospitalization rate per ICI recipient has declined over that same time period (25.0% in 2011 to 8.5% in 2018). The most common toxicities leading to hospitalization in our cohort were gastrointestinal (30.7%; n = 138), pulmonary (15.8%; n = 71), hepatic (14.2%; n = 64), endocrine (12.2%; n = 55), neurologic (8.4%; n = 38), cardiac (6.7%; n = 30), and dermatologic (4.4%; n = 20). Multivariable logistic regression revealed statistically significant increases in irAE admission risk for CTLA-4 monotherapy recipients (odds ratio [OR], 2.02; p < .001) and CTLA-4 plus PD-1 combination therapy recipients (OR, 1.88; p < .001), relative to PD-1/PD-L1 monotherapy recipients, and patients with multiple toxicity had a 5-fold increase in inpatient mortality. CONCLUSION: This study illustrates that cancer centers must be prepared to manage a wide variety of irAE types and that CTLA-4 and combination ICI regimens are more likely to cause irAE admissions, and earlier. In addition, admissions for patients with multi-organ involvement is common and those patients are at highest risk of inpatient mortality. IMPLICATIONS FOR PRACTICE: The number of patients admitted to Massachusetts General Hospital for immune-related adverse events (irAEs) has gradually increased every year and the most common admissions are for gastrointestinal (30.7%), pulmonary (15/8%), and hepatic (14.2%) events. Readmission rates are high (29% at 30 days, 49% at 180 days) and 64.2% have to permanently discontinue immune checkpoint inhibitor therapy. Importantly, multiple concurrent toxicities were seen in 21.6% (97/450) of irAE admissions and these patients have a fivefold increased risk of inpatient death.
Subject(s)
Antineoplastic Agents, Immunological , Neoplasms/drug therapy , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/adverse effects , Cohort Studies , Female , Hospitalization , Humans , Inpatients , Male , Massachusetts , Middle Aged , Retrospective StudiesABSTRACT
A 37-year-old woman presented to our rheumatology-dermatology clinic with a rash, muscle weakness and fatigue. She has had prior diagnoses of cutaneous lupus and lichen planus based on skin biopsies. She did not respond to topical steroids, hydroxychloroquine and dapsone. Clinically, she had sharply demarcated photo-distributed erythema over the upper back, chest and upper arms, along with hyperkeratotic follicular papules on bilateral upper arms, shoulders, posterior neck, behind the ears, chest including breasts, abdomen and right buttock. Investigations revealed a high titre ANA, elevated creatinine kinase, aldolase and positive anti-MJ/nuclear matrix protein 2 (NXP-2). A skin biopsy showed findings of connective tissue disease. The diagnosis of Wong-type dermatomyositis was made. She responded to therapy with mycophenolate mofetil, rituximab and IVIG.
Subject(s)
Dermatomyositis/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Rituximab/therapeutic use , Adult , Drug Therapy, Combination , Female , Glucocorticoids/therapeutic use , Humans , Prednisone/therapeutic useABSTRACT
In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral load peaks early and declines quickly after symptom onset. Severe coronavirus disease 2019 (COVID-19) is marked by aberrant innate and adaptive immune responses with an abnormal cytokine profile and multiorgan system dysfunction that persists well after viral clearance. A purely antiviral treatment strategy may therefore be insufficient, and antiviral agents have not shown a benefit later in the illness course. A number of immunomodulatory strategies are being tested, including corticosteroids, cytokine and anticytokine therapies, small molecule inhibitors, and cellular therapeutics. To date, the only drug to show a mortality benefit for COVID-19 in a randomized, controlled trial is dexamethasone. However, there remains uncertainty about which patients may benefit most and about longer-term complications, including secondary infections. Here, we review the immune dysregulation of severe COVID-19 and the existing data behind various immunomodulatory strategies, and we consider future directions of study.
Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , Humans , Immunity, Humoral , Immunomodulation , Randomized Controlled Trials as Topic , SARS-CoV-2ABSTRACT
BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Drug Treatment , Receptors, Interleukin-6/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Boston , COVID-19/mortality , Disease Progression , Double-Blind Method , Female , Humans , Intubation/statistics & numerical data , Male , Middle Aged , Respiratory Therapy , Treatment Failure , Young AdultABSTRACT
OBJECTIVE: Calcinosis is a debilitating complication of systemic sclerosis (SSc) with no effective treatments. We sought to identify clinical correlations and to characterize complications and disability associated with calcinosis in a multi-center, international cohort of SSc patients. METHODS: We established a cohort of 568 consecutive SSc patients who fulfill 2013 revised ACR/EULAR criteria at 10 centers within North America, Australia, and Mexico. Calcinosis was defined as subcutaneous calcium deposition by imaging and/or physical examination, or a clear history of extruded calcium. All patients completed the Scleroderma Health Assessment Questionnaire Disability Index and Cochin Hand Functional Scale. RESULTS: 215 (38%) patients had calcinosis. In multivariable analysis, disease duration (OR=1.24, p = 0.029), digital ischemia (OR=1.8, p = 0.002) and Acro-osteolysis (OR=2.97, p = 0.008) were significantly associated with calcinosis. In the subset of patients with bone densitometry (n = 68), patients with calcinosis had significantly lower median T-scores than patients without (-2.2 vs. -1.7, p = 0.004). The most common location of calcinosis lesions was the hands (70%), particularly the thumbs (19%) with decreasing frequency moving to the fifth fingers (8%). The most common complications were tenderness (29% of patients) and spontaneous extrusion of calcinosis through the skin (20%), while infection was rare (2%). Disability and hand function were worse in patients with calcinosis, particularly if locations in addition to the fingers/thumbs were involved. CONCLUSIONS: We confirmed a strong association between calcinosis and digital ischemia. Calcinosis in SSc patients most commonly affects the hands and is associated with a high burden of disability and hand dysfunction.
Subject(s)
Acro-Osteolysis , Calcinosis , Scleroderma, Systemic , Calcinosis/diagnostic imaging , Calcinosis/etiology , Hand , Humans , Ischemia , Scleroderma, Systemic/complicationsABSTRACT
There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID-19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID-19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID-19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach.
Subject(s)
Coronavirus Infections/drug therapy , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , COVID-19 , Datasets as Topic/standards , Heart/drug effects , Humans , Hydroxychloroquine/pharmacology , Immunity, Innate/drug effects , Pandemics , Randomized Controlled Trials as Topic/standardsABSTRACT
Oncologic treatment is being revolutionized by a burgeoning number of immune checkpoint inhibitors (ICPis). To date, seven ICPis have received Food and Drug Administration approval, targeting cytotoxic T-lymphocyte antigen, programmed cell death, or programmed cell death ligand. Adverse events associated with checkpoint inhibition have been described in the literature. Guidelines exist for the most common of these, but as the use of ICPis becomes more common, the number of patients presenting with rare events will increase. This article reviews the diagnosis and management of rare ocular, hematological, luminal gastrointestinal, and rheumatological toxicities arising from ICPi treatment. KEY POINTS: As the use of immune checkpoint inhibitors (ICPis) becomes more common, the number of rare immune-related adverse events (irAEs) will increase. A high level of suspicion is required to identify and treat these toxicities. Although it can be difficult to definitively attribute rare irAEs to ICPis, a temporal and mechanistic relationship and the absence of other etiologies should make the treating physician suspicious for a rare irAE. Certain rare irAEs, such as celiac disease, do not require treatment with glucocorticoids. Thus, differentiating this irAE from other gastrointestinal irAEs has important implications for treatment.
Subject(s)
Antineoplastic Agents/adverse effects , Aged , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Male , Middle AgedSubject(s)
Chest Pain/etiology , Lupus Erythematosus, Systemic/diagnosis , Lymph Nodes/pathology , Adult , Arthralgia/etiology , Biopsy , Cardiac Tamponade/diagnosis , Cardiac Tamponade/etiology , Diagnosis, Differential , Echocardiography , Humans , Lupus Erythematosus, Systemic/complications , Male , Pericardial Effusion/diagnostic imaging , Pericardial Effusion/etiology , Weight LossABSTRACT
BACKGROUND: The use of immune checkpoint inhibition (ICI) has revolutionized cancer treatment. However, these medications are associated with significant and potentially debilitating immune-related adverse events (irAEs). While certain toxicities have been well studied, rheumatic complications have been less widely recognized and characterized. METHODS: We report our experience of patients who were evaluated by rheumatology after the development of a suspected rheumatic irAE following ICI treatment. Cases of rheumatic irAEs were included if active rheumatic signs or symptoms developed during or after ICI treatment and were confirmed by a treating rheumatologist. RESULTS: Twenty-nine patients were evaluated by rheumatology for suspected rheumatic irAEs. Eighteen patients had confirmed toxicity including inflammatory arthritis (nâ¯=â¯12) and PMR (nâ¯=â¯6). Twelve patients had de novo toxicity and six had a flare of a pre-existing rheumatic condition. The onset of de novo toxicity occurred late into treatment (median 38 weeks), while patients with pre-existing rheumatic disease flared soon after initiation of ICI treatment (median 4.6 weeks). Management often required systemic or intra-articular steroids, with initiation of disease modifying anti-rheumatic drug (DMARD) therapy in those unable to wean off steroids. CONCLUSION: De novo rheumatic irAEs are generally delayed in onset after ICI initiation, while flares of pre-existing rheumatic conditions occur shortly after ICI initiation. Effective management often requires systemic corticosteroids as well as DMARDs in a subset of patients. Future prospective studies are needed to accurately describe the incidence and spectrum of rheumatic irAEs and to identify the most effective management strategies.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Arthritis, Psoriatic/chemically induced , Arthritis, Rheumatoid/chemically induced , Polymyalgia Rheumatica/chemically induced , Adult , Aged , Aged, 80 and over , Female , Humans , Lung Neoplasms/drug therapy , Male , Melanoma/drug therapy , Middle Aged , Prospective Studies , Skin Neoplasms/drug therapyABSTRACT
OBJECTIVES: Recent studies have shown an increase in both cardiovascular and all-cause mortality in ankylosing spondylitis (AS). We examined the potential survival benefit of statin use in AS within a general population context. METHODS: We performed an incident user cohort study with time-stratified propensity score matching using a UK general population database between 1 January 2000 and 31 December 2014. To account for potential confounders, we compared propensity score-matched cohorts of statin initiators and non-initiators using 1-year cohort accrual blocks. The variables used to create the propensity score model included disease duration, body mass index, lifestyle factors, comorbidities and medication use. RESULTS: Using unmatched AS cohorts, statin initiators (n=1430) showed a 43% higher risk of mortality than non-initiators (n=1430) (HR=1.43; 95% CI 1.12 to 1.84). After propensity score matching, patients with AS who initiated statins (n=1108) had 96 deaths, and matched non-initiators (n=1108) had 134 deaths over a mean follow-up of 5.3 and 5.1 years, respectively. This corresponded to mortality rates of 16.5 and 23.8 per 1000 person-years (PY), respectively, resulting in an HR of 0.63 (95% CI 0.46 to 0.85) and an absolute mortality rate difference of 7.3 deaths per 1000 PY (95% CI 2.1 to 12.5). CONCLUSION: This general population-based cohort study suggests that statin initiation is associated with a substantially lower risk of mortality among patients with AS. The magnitude of the inverse association appears to be larger than that observed in randomised trials of the general population and in population-based cohort studies of patients with rheumatoid arthritis.
Subject(s)
Cardiovascular Diseases/epidemiology , Cause of Death , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Spondylitis, Ankylosing/mortality , Cardiovascular Diseases/drug therapy , Cohort Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Propensity Score , Protective Factors , Survival Rate , United Kingdom/epidemiologyABSTRACT
Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are leading causes of morbidity and mortality in systemic sclerosis (SSc). As symptoms are often under-reported in SSc, early screening of ILD and PAH is of paramount importance, and early treatment may be associated with better clinical outcomes. Serologies are particularly helpful in identifying patients at risk for pulmonary involvement. Pulmonary function testing, high-resolution computed tomography of the chest and echocardiography are important tools in the initial screening of these patients. Extensive research has also led to an improved understanding of the mediators involved in the pathogenesis of ILD and PAH. As a result, there have been significant advances in the development of novel targeted therapeutics and an increase in the number of early-phase clinical trials in SSc.
Subject(s)
Hypertension, Pulmonary/etiology , Lung Diseases, Interstitial/etiology , Scleroderma, Systemic/complications , Echocardiography/methods , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/therapy , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/therapy , Mass Screening/methods , Respiratory Function Tests , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/therapy , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND: Dual lipid-lowering and anti-inflammatory properties of statins may lead to survival benefits in patients with rheumatoid arthritis (RA). However, data on this topic are limited, and the role of statins in RA remains unclear. OBJECTIVES: To examine the association of statin use with overall mortality among patients with RA in a general population context. METHODS: We conducted an incident user cohort study with time-stratified propensity score matching using a UK general population database. The study population included individuals aged ≥20â years who had a diagnosis of RA and had used at least one disease-modifying antirheumatic drug (DMARD) between January 2000 and December 2012. To closely account for potential confounders, we compared propensity score matched cohorts of statin initiators and comparators (non-initiators) within 1-year cohort accrual blocks. RESULTS: 432 deaths occurred during follow-up (mean 4.51â years) of the 2943 statin initiators for an incidence rate of 32.6/1000 person-years (PY), while the 513 deaths among 2943 matched comparators resulted in an incidence rate of 40.6/1000 PY. Baseline characteristics were well-balanced across the two groups. Statin initiation was associated with a 21% lower risk of all-cause mortality (HR=0.79, 95% CI 0.68 to 0.91). When we defined RA by its diagnosis code alone (not requiring DMARD use), the corresponding HR was 0.81 (95% CI 0.74 to 0.90). CONCLUSIONS: Statin initiation is associated with a lower risk of mortality among patients with RA. The magnitude of association is similar to that seen in previous randomised trials among the general population.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Arthritis, Rheumatoid/drug therapy , Cause of Death , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Propensity ScoreABSTRACT
OBJECTIVE: To determine the risk of venous thromboembolism (VTE) (pulmonary embolism [PE] and deep vein thrombosis [DVT]) in individuals with incident systemic sclerosis (SSc; scleroderma) in the general population. METHODS: Using a population database that includes all residents of British Columbia, Canada, we conducted a cohort study of all patients with incident SSc and up to 10 age-, sex-, and entry time-matched individuals from the general population. We compared incidence rates of PE, DVT, and VTE between the 2 groups according to SSc disease duration. We calculated hazard ratios (HRs), adjusting for confounders. RESULTS: Among 1,245 individuals with SSc (83% female, mean age 56 years), the incidence rates of PE, DVT, and VTE were 3.47, 3.48, and 6.56 per 1,000 person-years, respectively, whereas the corresponding rates were 0.78, 0.76, and 1.37 per 1,000 person-years among 12,670 non-SSc individuals. Compared with non-SSc individuals, the multivariable HRs among SSc patients were 3.73 (95% confidence interval [95% CI] 1.98-7.04), 2.96 (95% CI 1.54-5.69), and 3.47 (95% CI 2.14-5.64) for PE, DVT, and VTE, respectively. The age-, sex-, and entry time-matched HRs for PE, DVT, and VTE were highest during the first year after SSc diagnosis (32.77 [95% CI 6.60-162.75], 8.50 [95% CI 3.13-23.04], and 12.03 [95% CI 5.27-27.45], respectively). CONCLUSION: These findings provide population-based evidence that SSc patients are at a substantially increased risk of VTE, especially within the first year after SSc diagnosis. Increased monitoring for this potentially fatal outcome and its modifiable risk factors is warranted in this patient population.
Subject(s)
Pulmonary Embolism/etiology , Scleroderma, Systemic/complications , Venous Thrombosis/etiology , Adult , Aged , British Columbia/epidemiology , Cohort Studies , Female , Humans , Male , Middle Aged , Pulmonary Embolism/epidemiology , Risk Assessment , Scleroderma, Systemic/epidemiology , Venous Thrombosis/epidemiologyABSTRACT
Systemic sclerosis is a heterogeneous disease of unknown etiology with limited effective therapies. It is characterized by autoimmunity, vasculopathy, and fibrosis and is clinically manifested by multiorgan involvement. Interstitial lung disease is a common complication of systemic sclerosis and is associated with significant morbidity and mortality. The diagnosis of interstitial lung disease hinges on careful clinical evaluation and pulmonary function tests and high-resolution computed tomography. Effective therapeutic options are still limited. Several experimental therapies are currently in early-phase clinical trials and show promise.
Subject(s)
Lung Diseases, Interstitial/diagnosis , Scleroderma, Systemic/complications , Humans , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/physiopathology , Lung Diseases, Interstitial/therapyABSTRACT
OBJECTIVE: To perform a systematic review of the literature regarding the epidemiology of the association between systemic lupus erythematosus (SLE) and atherosclerotic cardiovascular disease (CVD), including the increased risk for CVD, as well as the risk factors responsible for development of CVD in patients with SLE. METHODS: We followed the PRISMA guidelines to systematically search the PubMed database from inception to June 2012. Studies were selected using predefined eligibility criteria, and 2 authors independently extracted data. The risk of bias was measured for each study using a domain-based assessment. RESULTS: We report on 28 studies that met criteria for inclusion in our analysis. We found strong epidemiologic evidence that SLE patients have an increased relative risk of CVD compared to controls. There is limited information regarding relative CVD mortality risks among SLE patients. Traditional CVD risk factors, including age, male sex, hyperlipidemia, smoking, hypertension, and CRP, are associated with CVD risk among SLE patients. Several SLE-specific factors, including disease activity and duration, and possibly specific manifestations and therapies, further increase risk. Several risk factors, such as disease activity and glucocorticoid use, are closely associated, making it difficult to disentangle their effects. CONCLUSIONS: CVD risk among SLE patients compared to the general population is at least doubled. While older SLE patients appear to have the highest absolute risks of CVD, young women have alarmingly high relative risks, given the rarity of CVD in the comparison general population. Both traditional and SLE-specific risk factors are important, although there are discrepancies within the literature.