Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine

Introduction: The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients. Methods: A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. Survival was modeled by left-truncated Kaplan-Meier estimation and Cox regression. Results: The 5- and 10-year survival estimates were 77% (95% CI = 66 to 85), and 62% (95% CI = 48 to 73), respectively, and the rates were similar for polymyositis and dermatomyositis. Survival between the sexes was similar through 5 years and significantly lower thereafter for males (10-year survival: 18% male, 73% female; P = 0.002 for 5- to 10-year interval). The sex disparity was restricted to the polymyositis group. Increased age at diagnosis and non-Caucasian race were associated with lower survival. Intravenous versus oral corticosteroid use was associated with a higher risk of death among Caucasians (HR = 10.6, 95% CI = 2.1 to 52.8). Early survival between patients treated with methotrexate versus azathioprine was similar, but survival at 10 years was higher for the methotrexate-treated group (76% vs 52%, P = 0.046 for 5- to 10-year interval). Conclusions: Patients treated initially with intravenous corticosteroids had higher mortality, which was likely related to disease severity. Both methotrexate and azathioprine showed similar early survival benefits as first-line immunosuppressive drugs. Survival was higher between 5 and 10 years in the methotrexate-treated group, but could not be confirmed in multivariable modeling for the full follow-up period. Other important predictors of longterm survival included younger age, female sex and Caucasian race.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90025/1/IIM_ART2012.pdf1611

The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome

HPA axis abnormalities in FM, CFS, and other stress-related disorders must be placed in a broad clinical context. We know that interventions providing symptomatic improvement in patients with FM and CFS can directly or indirectly affect the HPA axis. These interventions include exercise, tricyclic anti-depresssants, and serotonin reuptake inhibitors. There is little direct information as to how the specific HPA axis perturbations seen in FM can be related to the major symptomatic manifestations of pain, fatigue, sleep disturbance, and psychological distress. Since many of these somatic and psychological symptoms are present in other syndromes that exhibit HPA axis disturbances, it seems reasonable to suggest that there may be some relationship between basal and dynamic function of the HPA axis and clinical manifestations of FM and CFS. Veränderungen der Achse Hypothalamus-Hypophyse-Nebennierenrinde (HPA) beim Fibromyalgie-(FM) und Chronischem-Müdigkeits-Syndrom (CFS) sowie anderen Erkrankungen, bei denen Streßeinflüsse eine große Rolle zu spielen scheinen, müssen in einem größeren klinischen Kontext gesehen werden. Wir wissen, daß therapeutische Interventionen, die eine symptomatische Besserung bei Patienten mit FM und CFS bewirken, direkt oder indirekt Auswirkungen auf die HPA-Achse haben. Diese Interventionen schließen Bewegungstherapie, trizyklische Antidepressiva und Serotonin-Wiederaufnahme-Hemmer mit ein. Es ist wenig über die genauen Beziehungen zwischen den spezifischen Regulationsänderungen der HPA-Achse bei FM und den Hauptsymptomen wie Schmerz, Schwäche, Schlaftstörungen und psychologischer Streß bekannt. Da viele dieser somatischen und psychologischen Symptome auch bei anderen Syndromen vorkommen, welche Störungen der HPA-Achse zeigen, scheint es folgerichtig anzunehmen, daß zwischen den klinischen Manifestationen von FM und CFS Beziehungen zu basalen und dynamischen Funktionen der HPA-Achse bestehen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42464/1/393-57-S2-S67_8057s067.pd

Microsomal prostaglandin E synthase-1: the inducible synthase for prostaglandin E(2)

Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme that catalyzes the conversion of prostaglandin (PG)H(2 )to PGE(2). Proinflammatory stimuli markedly increase levels of mPGES-1 expression both in vivo and in vitro. mPGES-1 knockout studies and animal models of inflammatory arthritis also provide a strong basis for the contribution of mPGES-1 in the increased local production of PGE(2 )observed in inflammatory arthritis. The focus of this article is to review some recent advances in our understanding of mechanisms specific to the regulation of inducible mPGES-1 in inflammatory arthritis

Shunting of prostanoid biosynthesis in microsomal prostaglandin E synthase‐1 null embryo fibroblasts: regulatory effects on inducible nitric oxide synthase expression and nitrite synthesis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154471/1/fsb2fj066366fje.pd

Modeling bivariate longitudinal hormone profiles by hierarchical state space models

The hypothalamic-pituitary-adrenal (HPA) axis is crucial in coping with stress and maintaining homeostasis. Hormones produced by the HPA axis exhibit both complex univariate longitudinal profiles and complex relationships among different hormones. Consequently, modeling these multivariate longitudinal hormone profiles is a challenging task. In this paper, we propose a bivariate hierarchical state space model, in which each hormone profile is modeled by a hierarchical state space model, with both population-average and subject-specific components. The bivariate model is constructed by concatenating the univariate models based on the hypothesized relationship. Because of the flexible framework of state space form, the resultant models not only can handle complex individual profiles, but also can incorporate complex relationships between two hormones, including both concurrent and feedback relationship. Estimation and inference are based on marginal likelihood and posterior means and variances. Computationally efficient Kalman filtering and smoothing algorithms are used for implementation. Application of the proposed method to a study of chronic fatigue syndrome and fibromyalgia reveals that the relationships between adrenocorticotropic hormone and cortisol in the patient group are weaker than in healthy controls

Incidence and US Costs of Corticosteroid-Associated Adverse Events: A Systematic Literature Review

OBJECTIVE: The objective of this systematic literature review was to evaluate the incidences and risks for adverse events (AEs) associated with oral and parenteral corticosteroids. An assessment was performed to estimate the costs of such AEs. METHODS: A systematic review of literature published from 2007 to 2009 was conducted to identify the incidence rates and risk ratios of corticosteroid-related AEs. The review protocol was developed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The literature search was expanded to include additional search terms for psychiatric conditions, infections, and peptic ulcers. Costs obtained from a separate narrative literature review were applied to AEs likely to affect third-party payers in the United States. RESULTS: A total of 357 publications were identified from the primary (n = 323) and secondary (n = 34) searches. Of these, 310 were excluded because they did not evaluate AEs related to corticosteroids, were an excluded publication type, or for other reasons. A final list of 47 studies were used for data extraction. Across patient populations, the most frequently reported corticosteroid-associated AEs were psychiatric events, infections, gastric conditions, and fractures. Corticosteroid-associated AEs reported to occur at an incidence >30% were sleep disturbances, lipodystrophy, adrenal suppression, metabolic syndrome, weight gain, and hypertension. Vertebral fractures were reported at an incidence of 21% to 30%. Dose-response relationships were documented for fractures, acute myocardial infarction, hypertension, and peptic ulcer. The costs of managing AEs that may occur with corticosteroids can be substantial. The literature reported 1-year per-patient costs of up to $26,471.80 for nonfatal myocardial infarction, and per-event costs as high as$18,357.90 for fracture. The findings from the present review should be interpreted cautiously due to several limitations, including the retrospective design of most of the studies identified, risk for confounding due to underlying disease activity or patient population, and the relatively small number of studies that reported each AE association. As this cost analysis was preliminary, a comprehensive pharmacoeconomic analysis should be undertaken to confirm the findings. CONCLUSION: Based on the findings from this review, systemic corticosteroids are a common cause of AEs that may be costly to payers

Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome

Researchers studying fibromyalgia strive to identify objective, measurable biomarkers that may identify susceptible individuals, may facilitate diagnosis, or that parallel activity of the disease. Candidate objective measures range from sophisticated functional neuroimaging to office-ready measures of the pressure pain threshold. A systematic literature review was completed to assess highly investigated, objective measures used in fibromyalgia studies. To date, only experimental pain testing has been shown to coincide with improvements in clinical status in a longitudinal study. Concerted efforts to systematically evaluate additional objective measures in research trials will be vital for ongoing progress in outcome research and translation into clinical practice

Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine

Abstract Introduction The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients. Methods A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. Survival was modeled by left-truncated Kaplan-Meier estimation and Cox regression. Results The 5- and 10-year survival estimates were 77% (95% CI = 66 to 85), and 62% (95% CI = 48 to 73), respectively, and the rates were similar for polymyositis and dermatomyositis. Survival between the sexes was similar through 5 years and significantly lower thereafter for males (10-year survival: 18% male, 73% female; P = 0.002 for 5- to 10-year interval). The sex disparity was restricted to the polymyositis group. Increased age at diagnosis and non-Caucasian race were associated with lower survival. Intravenous versus oral corticosteroid use was associated with a higher risk of death among Caucasians (HR = 10.6, 95% CI = 2.1 to 52.8). Early survival between patients treated with methotrexate versus azathioprine was similar, but survival at 10 years was higher for the methotrexate-treated group (76% vs 52%, P = 0.046 for 5- to 10-year interval). Conclusions Patients treated initially with intravenous corticosteroids had higher mortality, which was likely related to disease severity. Both methotrexate and azathioprine showed similar early survival benefits as first-line immunosuppressive drugs. Survival was higher between 5 and 10 years in the methotrexate-treated group, but could not be confirmed in multivariable modeling for the full follow-up period. Other important predictors of long-term survival included younger age, female sex and Caucasian race.http://deepblue.lib.umich.edu/bitstream/2027.42/112905/1/13075_2011_Article_3467.pd