Duration Of Corticosteroid Use Research Articles

Corticosteroid Therapy in the Age of Infliximab: Acute and 1-Year Outcomes in Newly Diagnosed Children With Crohn’s Disease

The aim of this study was to describe 3-month and 1-year outcomes of children with Crohn's disease (CD) treated with corticosteroids within 30 days of diagnosis, with particular emphasis on the influence of infliximab on these outcomes. We also aimed to determine whether there are clinical or laboratory characteristics associated with corticosteroid therapy outcomes. Data from 109 children were drawn from a multicenter observational registry that was started in 2002. Clinical characteristics and data on corticosteroid and other therapies were recorded prospectively. Corticosteroid therapy outcomes at 3 months were defined as complete acute response, partial response, or corticosteroid resistance. At 1 year, corticosteroid responsiveness, dependence, and surgical rates were determined. Infliximab's influence on short- and long-term outcomes also was investigated. At 3 months, 65 of 109 (60%) patients had a complete acute response to corticosteroids, 26 (24%) had a partial response, and 18 (17%) were corticosteroid resistant. At 1 year, 61% were corticosteroid responsive, 31% were corticosteroid dependent, and 8% required surgery. Irrespective of the duration of corticosteroid treatment, 16 of 24 of corticosteroid-dependent/resistant patients rapidly discontinued corticosteroids after starting infliximab. No clinical or laboratory characteristics at diagnosis predicted short-term outcome. Growth impairment at diagnosis increased risk for corticosteroid dependence or surgery at 1 year. At 3 months, 84% of children had a complete or partial response to corticosteroids. However, despite concomitant immunomodulators, at 1 year 31% were corticosteroid dependent and 8% required surgery. Infliximab improves outcomes of corticosteroid-dependent/resistant patients because the duration of corticosteroid use can be controlled by initiating treatment with infliximab.

Maintenance Immunosuppression Use and the Associated Risk of Avascular Necrosis After Kidney Transplantation in the United States

Avascular necrosis (AVN) after renal transplantation has been largely attributed to the use of corticosteroids. However, other risk factors such as microvascular thrombosis and hyperlipidemia have been well described and may be of increased importance in the era of early steroid cessation and avoidance. We hypothesized that maintenance immunosuppressive medications known to be associated with these risk factors for AVN would also be associated with a higher risk of AVN. By using the U.S. Renal Data System database, we studied 27,772 primary patients on Medicare who received a solitary kidney transplant between January 1, 1996, and July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHRs) for patient- and transplant-related factors (including allograft rejection) with Medicare claims for AVN. The intensity and duration of corticosteroid use could not be assessed. Among patients who were prescribed sirolimus at discharge, 3.5% of patients who received the combination of sirolimus-cyclosporine A (CsA) demonstrated AVN, compared with 1.4% of patients who received the combination of sirolimus-tacrolimus (P=0.06 by chi). In Cox regression, CsA use (vs. tacrolimus) (AHR 1.36, 95% confidence interval, 1.09-1.71) was independently associated with an increased risk of AVN. Sirolimus use showed a trend toward significance (AHR 1.59, 95% confidence interval, 0.99-2.56), with no significant interaction with CsA. Compared with other maintenance immunosuppression, AVN was significantly more common after use of CsA prescribed at the time of discharge for renal transplantation. Whether this increased risk of AVN was directly attributable to hyperlipidemia, microvascular thrombosis, or differences in corticosteroid dosing could not be determined.

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Corticosteroids.

Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use.

Few data are available regarding vertebral fracture risk in patients treated with oral corticosteroids. The aim of this study was to determine the prevalence and the role of risk factors such as age, bone mineral density (BMD), and corticosteroid use for vertebral deformity in patients receiving long-term corticosteroid therapy. Thoracolumbar x-ray films, BMD, and details on corticosteroid use were obtained on 229 consecutive patients treated with long-term corticosteroid regimens (> or = 6 months of prednisone, > or = 5mg/d or equivalent) seen at 4 referral centers. Comparisons were made with a population control group of 286 male and female controls not taking corticosteroids (aged > or = 60 years). Sixty-five patients (28%) had at least 1 vertebral deformity and 25 (11%) had 2 or more vertebral deformities. Older age, independent of BMD, was a significant risk factor for deformity. Patients aged 70 to 79 years had a 5-fold increased risk of deformity compared with patients younger than 60 years (odds ratio, 5.13; 95% confidence interval, 2.03-13.0). Compared with the population controls, the prevalence of deformities increased to a greater extent with each decade of age in the corticosteroid group (P =.005). Mean lumbar spine and femoral neck BMD Z scores were lower in the steroid-treated patients with deformities compared with the nonsteroid control group with deformities. When the effects of age, sex, body mass index, and duration of corticosteroid use were adjusted for in logistic regression analysis, low BMD was a modest predictor of deformity (for a 1-SD decrease in lumbar spine BMD: odds ratio, 1.31; 95% confidence interval, 1.02-1.68) and for a 1-SD decrease in femoral neck BMD: odds ratio, 1.77; 95% confidence interval, 1.07-2.94). The combination of increasing age and corticosteroid use is associated with a marked increase in the risk of vertebral deformity. Elderly patients commencing long-term corticosteroid therapy should be considered for antiosteoporotic therapy independently of their BMD. Arch Intern Med. 2000;160:2917-2922

Frequency of fractures in women with systemic lupus erythematosus: comparison with United States population data.

To describe the frequency of self-reported fractures in a large population-based cohort of women with lupus, to compare the frequency of self-reported fractures between lupus patients and women of similar age in the general population by use of data from the 1994 National Health Interview Survey (NHIS), and to describe the associated risk factors for fracture in women with lupus. This study is a secondary analysis of data collected to assess cardiovascular risk in women with lupus. Fractures and associated risk factors were ascertained by self report in this retrospective cohort study of 702 living women with lupus who were followed up for 5,951 person-years. Self-reported fractures were verified in a subset of patients. A Weibull regression model was used to assess risk factors associated with time from lupus diagnosis to fracture in the univariate and multivariate analyses. Age-specific standard morbidity ratios (SMRs) were calculated to determine whether fracture occurrence was greater than expected in women with lupus. Eighty-six (12.3%) of 702 women reported at least 1 fracture following the diagnosis of lupus. The sites of the first fracture were the leg (n = 32), foot (n = 16), arm (n = 15), spine (n = 9), rib (n = 7), hip (n = 2), pelvis (n = 2), hand (n = 1), shoulder (n = 1), and finger (n = 1). Fracture risk was increased in the lupus cohort compared with women of similar age from the United States population, using weighted data from the 1994 NHIS (SMR 4.7; 95% confidence interval 3.8, 5.8). Variables in the univariate analysis that were significantly associated (P < 0.05) with time from lupus diagnosis to fracture were older age at lupus diagnosis, longer disease duration, longer duration of corticosteroid use, less use of oral contraceptives, and menopause status. In the multivariate analysis, independent determinants of time from lupus diagnosis to fracture were older age at lupus diagnosis and longer duration of corticosteroid use. Fractures occurred in 12.3% of lupus patients who were followed up for 5,951 person-years. There was nearly a 5-fold increase in fracture occurrence in the women with lupus compared with women from the US population. Older age at lupus diagnosis and longer use of corticosteroids were associated with time from lupus diagnosis to fracture. With increased life expectancy of lupus patients, fracture occurrence is a major threat to the health of these women. Prevention strategies must be directed toward minimizing the occurrence of fractures in these patients.

Growth Failure in Pediatric Inflammatory Bowel Disease

SummaryTo assess whether children with inflammatory bowel disease (IBD) develop permanent impairment of linear growth, we analyzed records from 48 young adults who had IBD during childhood or early adolescence (Tanner I‐III; 11.8 ± 2.4 years old at diagnosis). All were fully grown (Tanner V; 21.1 ± 3.0 years) at last examination. Adult heights were predicted from data obtained at or shortly after the diagnosis of IBD by three methods: height for age percentile, the Bailey‐Pinneau (BP), and Roche‐Wainer‐Thissen (RWT) methods. Predicted adult heights were then compared with the actual ultimate height of each subject. Permanent growth failure occurred in 19–35% of subjects, depending upon the method used to assess growth. Overall, 31% (15 of 48) of the subjects had deficits of adult height identified by two or more methods, including 14 of 38 (37%) of those with Crohn's disease but only one of 10 with ulcerative colitis. Age at diagnosis of IBD, age at last examination, age at cessation of linear growth, and site of IBD did not differ between impaired and normal growth groups. Duration of corticosteroid use was longer (p &lt; 0.05) in growth‐impaired subjects. In addition, although 60% of all subjects had periods of poor growth that put them in height‐for‐age percentiles two or more major growth channels below previous percentiles, only 19% remained at these levels upon achieving their final adult heights. Permanent impairment of linear growth leading to clinically meaningful deficits of ultimate adult height is common in patients with IBD in childhood or early adolescence. New therapeutic approaches are needed to address this problem.

Growth failure in pediatric inflammatory bowel disease.

To assess whether children with inflammatory bowel disease (IBD) develop permanent impairment of linear growth, we analyzed records from 48 young adults who had IBD during childhood or early adolescence (Tanner I-III; 11.8 +/- 2.4 years old at diagnosis). All were fully grown (Tanner V; 21.1 +/- 3.0 years) at last examination. Adult heights were predicted from data obtained at or shortly after the diagnosis of IBD by three methods: height for age percentile, the Bailey-Pinneau (BP), and Roche-Wainer-Thissen (RWT) methods. Predicted adult heights were then compared with the actual ultimate height of each subject. Permanent growth failure occurred in 19-35% of subjects, depending upon the method used to assess growth. Overall, 31% (15 of 48) of the subjects had deficits of adult height identified by two or more methods, including 14 of 38 (37%) of those with Crohn's disease but only one of 10 with ulcerative colitis. Age at diagnosis of IBD, age at last examination, age at cessation of linear growth, and site of IBD did not differ between impaired and normal growth groups. Duration of corticosteroid use was longer (p < 0.05) in growth-impaired subjects. In addition, although 60% of all subjects had periods of poor growth that put them in height-for-age percentiles two or more major growth channels below previous percentiles, only 19% remained at these levels upon achieving their final adult heights. Permanent impairment of linear growth leading to clinically meaningful deficits of ultimate adult height is common in patients with IBD in childhood or early adolescence. New therapeutic approaches are needed to address this problem.