Cumulative Glucocorticoid Dose Research Articles

Glucocorticoid Dose-Dependent Risk of Type 2 Diabetes in Six Immune-Mediated Inflammatory Diseases: A Population-Based Cohort Analysis

Background: In immune-mediated inflammatory diseases, there is a lack of precise estimates of glucocorticoid dose-response diabetes risk that consider changes in prescribed dose over time and disease activity. Methods: Population-based longitudinal analysis of electronic health records from the UK Clinical Practice Research Datalink, linked to hospital admissions and the mortality registry (1998-2017). We included 100,722 adult patients without prior diabetes history, diagnosed with giant cell arteritis or polymyalgia rheumatica (n=32,593), inflammatory bowel disease (n=29,272), rheumatoid arthritis (n=28,365), vasculitis (n=6,082), or systemic lupus erythematosus (n=4,410). We estimated risks and hazard ratios of type 2 diabetes associated with time-variant daily and total cumulative prednisolone-equivalent glucocorticoid dose using Cox regression methods. Findings: Average patient age was 58·6 years, 65,469 (65·0%) were women and 8,858 (22·6%) had a BMI ≥30 kg/m2. Overall, 8,137 (8·1%) people developed type 2 diabetes after a median follow-up of 4·9 years. At 1 year, the cumulative risk of diabetes increased from 0·9% during periods of non-use to 5·0% when the daily prednisolone-equivalent dose was ≥25·0mg. We found strong dose-dependent associations for all immune-mediated diseases, BMI levels and underlying disease duration, even after controlling for periods of active systemic inflammation. Adjusted hazard ratio [HR] for a <5·0mg daily dose vs. non-use was 1·90, 95%CI 1·44-2·50; range 1·70 for rheumatoid arthritis to 2·93 for inflammatory bowel disease. Interpretation: We report dose-dependent risks of type 2 diabetes associated with glucocorticoid use for six common immune-mediated inflammatory diseases. These results underline the need for regular diabetic risk assessment and testing during glucocorticoid therapy in these patients. Funding Statement: This work was partly supported by the Medical Research Council TARGET Partnership Grant (Treatment According to Response in Giant cEll arTeritis) (MR/N011775/1). JW is supported by the NIHR infrastructure @ Leeds. SLM was supported by a NIHR Clinician Scientist Fellowship. Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare no support from any organisation for the submitted work except for SLM who received: salary support from NIHR (Clinician Scientist Fellowship) during the period of work reported here; advisory board fees from Roche in 2015 and conference attendance from Roche in 2019; investigator or sub-investigatory on industry-sponsored clinical trials (Sanofi, Roche, GSK) and consultancy on behalf of the University of Leeds (without receiving personal income) to Roche and Sanofi. SLM is Patron of the patient support charity PMRGCAuk. Ethics Approval Statement: The Independent Scientific Advisory Committee for Medicines and Healthcare products Regulatory Agency database research (ISAC) approved the study (reference 16_146).

Height and sexual maturation in girls with juvenile idiopathic arthritis

ObjectiveTo evaluate height, sexual maturation, and the difference between final and expected height in girls with juvenile idiopathic arthritis and no glucocorticoid treatment for at least six months, as compared to a group of healthy girls. MethodsThis cross-sectional study involved 44 girls with juvenile idiopathic arthritis, diagnosed according to the International League of Associations for Rheumatology criteria, and 59 healthy controls aged between 8 and 18 (incomplete) years with no comorbid chronic diseases. Demographic data were collected from all participants, and disease and treatment variables were compiled for the patient group. Anthropometric measurements were converted into Z-scores based on World Health Organization standards. Sexual maturation was classified according to Tanner stages. ResultsBody mass index and height Z-scores were lower in girls with juvenile idiopathic arthritis as compared to control participants. These values differed significantly in Tanner stage II. Three (6.8%) girls with juvenile idiopathic arthritis had height-for-age Z-scores <−2 (short stature). Girls with polyarticular juvenile idiopathic arthritis and higher cumulative glucocorticoid doses were significantly more likely to present with short stature. The percentage of prepubertal girls in the juvenile idiopathic arthritis group was significantly higher than that observed in the control group, (p=0.012). Age of menarche, adult height, and the difference between actual and expected height did not differ between groups. ConclusionThese findings suggest that even six months after the suspension of glucocorticoid treatment, children with polyarticular/systemic juvenile idiopathic arthritis subtypes are still susceptible to low height and delayed puberty.

Influence of therapy on the development of long-term articular and extra-articular damages in adult patients with juvenile idiopathic arthritis

Aim of the research: to evaluate the effect of therapy on the development of articular and extra-articular damages in adult patients with JIA.Materials and methods: the study included 163 patients aged &gt;18 years, with a JIA according to the ILAR classification. The study did not include patients with disease duration &lt;3 years. The JADAS-10 disease activity, functional capacity (HAQ), articular (JADI-A) and extra-articular (JADI-E) damages of JIA were evaluated. The received therapy, a dose and duration of reception of various medications were analyzed.Results. JADI-A&gt;1 was detected in 36.9 %, and JADI-E&gt;1 was detected in 30.7 % of patients. Remission was diagnosed in 37 (41.6 %) patients with JIA. Most patients (67 %) had previously taken glucocorticoids (GC). Only 25 % of patients received GC at the time of observation, 28 (17.2 %) received only non-steroidal anti-inflammatory drugs (NSAIDs), 134 (82.2 %) – disease-modifying anti-rheumatic drugs (DMARDs). Biological therapy (BT) was received earlier or at the time of the examination in 23.9 % of patients. JADI-A was more frequently observed in RF-negative polyarthritis (47.1 % of patients vs 15.5 %, p&lt;0.05). Presence of articular damages (JADI-A&gt;1) in patients with persistent oligoarthritis was observed in 16.7 % of patients vs in 31.1 % without long-term joint damages (p&lt;0.05). Extra-articular damages (JADI-E&gt;1) were observed more often in RF-negative polyarthritis (in 36 % of patients vs 20.4 %, p&lt;0.05). In patients without articular (JADI-A&lt;1, 33.0 % vs. 5 %, p&lt;0.05) and extra-articular damages (JADI-E&lt;1, 30.1 % vs 6 %, p&lt;0.05) remission was diagnosed more often. Patients with JADI-A&gt;1 and JADI-E&gt;1 had higher degree of JADAS activity (p&lt;0.05) and a worse functional capacity for HAQ (p&lt;0.05). Patients with long-term extra-articular damages in adulthood were more likely to take GC in history or continued to take GC than patients without extra-articular damages (p&lt;0.01), they received longer GC (p&lt;0.01) and the cumulative dose of GC was higher (p&lt;0.01). However, both groups did not differ in the prescribing BT. Although a difference was found both in the administration of DMARDs, in the duration of treatment with DMARDs and the number of DMARDs assigned sequentially or in parallel in patients with long-term extra-articular damages (p&lt;0.05). Patients with extra-articular damages needed intensification of therapy with BT more often (p &lt;0.05) than patients without JADI-E.Conclusions: the presence of JIA in childhood leads to the development of articular damages in adulthood. These damages are observed more often in patients with RF-positive and RF-negative poly-arthritic JIA than with enthesitis-associated arthritis JIA and JIA with extended oligoarthritis. Extra-articular damages were developed in RF-positive and RF-negative poly-arthritic JIA more often than in oligoarthritic JIA and enthesitis-associated arthritis JIA. The development of long-term articular and extra-articular damages in adulthood is associated with a history of GC intake (p&lt;0.01) and usage of GC at the time of examination (p&lt;0.01), with a longer duration of GC intake (p&lt;0.01) and a higher cumulative dose of GC (p&lt;0.01). In order to reduce the development of long- term articular and extra-articular damages in adulthood DMARDs and BT should be more often administrated, as well as to avoid long- term use and high doses of GC

No evidence of overweight in long‐term survivors of childhood cancer after glucocorticoid treatment

Glucocorticoids can lead to weight gain during cancer treatment, but to the authors' knowledge, little is known regarding their long-term effects in childhood cancer survivors (CCS). As part of the Swiss Childhood Cancer Survivor Study, the authors sent a questionnaire to CCS aged <21 years at diagnosis who were residing in Switzerland, had survived ≥5 years, and were aged 15 to 45 years at the time of the survey. Cumulative doses of glucocorticoids were assessed from medical records and study protocols and body mass index was calculated from self-reported height and weight at the time of the survey. The authors compared the prevalence of overweight between CCS, their siblings, and the general population (Swiss Health Survey [SHS]) and investigated the association between overweight and treatment-related risk factors using multivariable logistic regression. The study included 1936 CCS, 546 siblings, and 9591 SHS participants. The median age of the CCS at the time of the survey was 24 years (interquartile range, 20-31 years) and the median time since diagnosis was 17 years (interquartile range, 12-22 years). At the time of the survey, approximately 26% of CCS were overweight, a percentage that was comparable to that among siblings (24%) and the SHS participants (25%). The prevalence of overweight was 24% in CCS treated with glucocorticoids only (686 CCS), 37% in those treated with cranial radiotherapy (CRT) (127 CCS), and 49% in those who received treatment with both glucocorticoids and CRT (101 CCS) (P < .001). The authors found no evidence of a dose-response relationship between cumulative glucocorticoid doses and overweight and no evidence that CRT modified the effect of the cumulative glucocorticoid dose on overweight. The results of the current study suggest that glucocorticoids used for the treatment of childhood cancer are not associated with long-term risk of overweight.

Does leflunomide have a role in giant cell arteritis? An open-label study

Glucocorticoid monotherapy has been the mainstay treatment of giant cell arteritis (GCA) for decades. We aimed to evaluate the role of leflunomide as a steroid-sparing agent in GCA. This open-label study included incipient GCA patients followed for at least 48 weeks at a single secondary/tertiary rheumatology centre. At the time of diagnosis, patients received glucocorticoids. At week 12 of follow-up, leflunomide 10 mg qd was recommended as an adjunctive therapy to all patients without contraindications. The decision to start the leflunomide was patient-dependent. The number of relapses, a cumulative glucocorticoid dose during follow-up and treatment-related adverse events (AE) were recorded and compared between glucocorticoid-only and leflunomide groups. Seventy-six patients (65.8% female, median (IQR) age 73.7 (66.1–78.8) years) were followed for a median (IQR) 96 (86–96) weeks. Thirty out of 76 (39.5%) patients received leflunomide at week 12 (leflunomide group); the others continued treatment with glucocorticoid (glucocorticoid-only group). During the first 48 weeks of follow-up, 22 patients relapsed, 4 (13.3%) in leflunomide group and 18 (39.1%) in glucocorticoid-only group. The difference was statistically significant (p = 0.02; NNT 3.9 (95% CI 2.2–17.4)). Furthermore, 17/30 (56.7%) patients in the leflunomide group managed to stop glucocorticoid at week 48 (with one relapse (5.9%) shortly afterwards). The cumulative glucocorticoid dose at the last visit was lower in the leflunomide group than in the glucocorticoid-only group (p = 0.01). Our findings indicate the steroid-sparing effect of leflunomide in GCA.

Prevalence of osteoporosis and osteopenia in a population of patients with inflammatory bowel diseases from the Wielkopolska Region

Introduction The incidence of osteoporosis in patients with inflammatory bowel disease (IBD) varies across different populations. Objectives The aim of this study was to evaluate the prevalence of osteoporosis in Polish patients with IBD, as well as the effect of the body mass index (BMI), disease duration, the number of hospital stays, and the use of glucocorticoids on bone mineral density (BMD). Patients and methods BMD of 208 patients with IBD (103 with Crohn disease [CD] and 105 with ulcerative colitis [UC]) and 41 healthy controls was measured using dual‑energy X‑ray absorptiometry. The association of BMD with the other parameters was analyzed using statistical methods. Results Osteoporosis of the lumbar (L2-L4) spine (T‑score) was observed in 11.7% of patients with CD and in 3.8% of those with UC, whereas that of the femoral neck (FN), in 5.8% and 2.9% of the patients with CD and UC, respectively. Osteopenia occurred in 35.9% (FN) and 36.9% (L2-L4) of CD patients, and in 25.7% (FN) and 29.5% (L2-L4) of UC patients. In CD patients, BMI was associated with lumbar and femoral BMD and with L2-L4 T‑score, whereas FN T‑score correlated with BMI. In UC patients, the cumulative glucocorticoid dose correlated with L2-L4 T‑score, FN BMD, FN T‑score, and FN Z‑score; the disease duration correlated with FN BMD, while the FN T‑score, with the number of hospital stays and FN BMD. Conclusions Osteoporosis and osteopenia are frequent in Polish patients with IBD. BMD correlated with BMI in all patients. In UC patients, BMD was associated with the cumulative glucocorticoid dose, disease duration, and number of hospital stays.

Adrenal Suppression in Infants Treated with Topical Ocular Glucocorticoids

To analyze the incidence of adrenal suppression and the glucocorticoid (GC) dose per kilogram body weight given in infants treated with standard protocol for topical ophthalmic GCs after congenital cataract surgery. Retrospective, consecutive case series. All children younger than 2 years of age who underwent operation for congenital cataract between January 2011 and May 2015 in 1 center. Patient charts were reviewed to collect data on results and timing of a standard corticotropin (adrenocorticotropic hormone [ACTH]) stimulation test and GC dose per kilogram body weight. Incidence of adrenal suppression in children tested on GC treatment. Glucocorticoid dose per kilogram body weight. Among 26 consecutive infants, 15 (58%) were tested while they were still on GC treatment. Ten of these 15 infants (67%) had adrenal suppression, 2 of whom had obvious clinical signs of Cushing's syndrome and 1 of whom had signs of Addisonian crises during general anesthesia. Eleven of the 26 infants (42%) were tested at a median time of 21 days (range, 6-89) after treatment cessation, and they all had normal test results. Children with suppressed adrenal function had received cumulative GC doses per body weight that were significantly higher the last 5 days before testing compared with children with normal test results. Infants with adrenal suppression were treated with hydrocortisone replacement therapy. Adrenal function recovered after a median of 3.1 months (range, 2.3 months to 2.3 years). Two thirds of the infants tested during treatment with a standard GC protocol after congenital cataract surgery showed adrenal suppression. There was a significant association between the cumulative daily dose of GCs and the test result. Because adrenal suppression is a serious but treatable condition, we recommend a systematic assessment of adrenal function in infants treated with doses of topical ocular GCs comparable to our regimen and careful evaluations of other treatment regimens.

Bone Morbidity and Recovery in Children With Acute Lymphoblastic Leukemia: Results of a Six-Year Prospective Cohort Study.

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non-VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z-score predicted both VF and non-VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children. Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2], p = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0], p = 0.01). VF and low LS BMD Z-score at baseline as well as glucocorticoid exposure predicted incident VF and non-VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse, because these children are at greatest risk for incident VF and subsequent residual vertebral deformity. © 2018 American Society for Bone and Mineral Research.

Risk Associated with Cumulative Oral Glucocorticoid Use in Patients with Giant Cell Arteritis in Real-World Databases from the USA and UK.

IntroductionTreatment of giant cell arteritis (GCA) involves immediate initiation of high-dose glucocorticoid therapy with slow tapering of the dose over many months. Chronic exposure to glucocorticoids is associated with serious comorbidities. The objective of this analysis was to determine the glucocorticoid exposure and risk of glucocorticoid-related adverse events (AEs) in real-world patients with GCA.MethodsData from the Truven Healthcare MarketScan® database (from January 1, 2000, to June 30, 2015) and the Clinical Practice Research Datalink (CPRD; from January 1, 1995, to August 31, 2013) were used to retrospectively analyze patients aged ≥ 50 years with GCA in the USA and UK, respectively. Outcomes included oral glucocorticoid use (cumulative prednisone-equivalent exposure), glucocorticoid-related AEs and the association of AE risk with glucocorticoid exposure over 52 weeks.ResultsOf the 4804 patients in the US MarketScan database and 3973 patients in the UK CPRD database included, 71.3 and 74.6% were women and mean age was 73.4 and 73.0 years, respectively. Median starting glucocorticoid dose and cumulative glucocorticoid dose at 52 weeks were 20–50 mg/day and 4000–4800 mg, respectively. The most frequent glucocorticoid-related AEs were hypertension and eye, bone health, and glucose tolerance conditions. In the first year after diagnosis, the likelihood of any glucocorticoid-related AE was significantly increased for each 1 g increase in cumulative glucocorticoid dose in the US and UK cohorts (odds ratio [95% CI], 1.170 [1.063, 1.287] and 1.06 [1.03, 1.09], respectively; P < 0.05 for both). Similar trends were observed for the risk of glucocorticoid-related AEs over full follow-up (mean, USA: 3.9 years, UK: 6.3 years).ConclusionsIn real-world patients with GCA, increased cumulative glucocorticoid exposure was associated with an increased risk of glucocorticoid-related AEs.FundingF. Hoffmann-La Roche Ltd.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s40744-018-0112-8) contains supplementary material, which is available to authorized users.

Ovarian reserve in young juvenile idiopathic arthritis patients

Objectives: Juvenile idiopathic arthritis (JIA) occurs during reproductive age, however, there are no systematic data regarding ovarian function in this disease.Methods: Twenty-eight post-pubertal JIA patients and age-matched 28 healthy controls were studied. Complete ovarian function was assessed during the early follicular phase of the menstrual cycle including anti-Müllerian hormone (AMH), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) by ovarian ultrasound, and anti-corpus lutheum antibodies (anti-CoL). Demographic data, menstrual abnormalities, disease parameters and treatment were also evaluated.Results: The mean current age (22.6 ± 6.59 vs. 22.5 ± 6.59 years, p = .952) was similar in JIA patients and healthy controls with a higher median menarche age [13(8–16) vs. 12(8–14) years, p = .029]. A lower median AMH levels [2.65(0.47–9.08) vs. 4.83(0.74–17.24) ng/mL, p = .029] with a higher LH [8.44 ± 4.14 vs. 6.03 ± 2.80 IU/L, p = .014] and estradiol levels [52.3(25.8–227.4) vs. 38.9(26.2–133.6) pg/mL, p = .008] were observed in JIA compared to control group. Anti-CoL and AFC were similar in both groups (p > .05). Further analysis of JIA patients revealed that current age, disease duration, number of active/limited joints, ESR, CRP, patient/physician VAS, JADAS 71, DAS 28, CHAQ, HAQ, patient/parents PedsQL, PF-SF 36, cumulative glucocorticoid and cumulative methotrexate doses were not correlated with AMH, FSH, estradiol levels or AFC (p > .05).Conclusion: The present study was the first to suggest diminished ovarian reserve, not associated to hypothalamic pituitary gonadal axis, in JIA patients during reproductive age. The impact of this dysfunction in future fertility of these patients needs to be evaluated in prospective studies.

Tocilizumab in the treatment of giant cell arteritis.

Giant cell arteritis is a systemic vasculitis of large vessels, manifesting mainly as temporal arteritis or large vessel vasculitis of the aorta and its branches. Glucocorticoid therapy is essential and so far had to be continued over a period of 1.5-2years, resulting in relevant morbidity through adverse effects. With the approval of tocilizumab, an effective glucocorticoid sparing option is now available. In two randomized controlled trials, a profound reduction of cumulative glucocorticoid dose, prolonged relapse-free remission and reduced number of adverse events in the treatment groups have been demonstrated. Therefore, tocilizumab constitutes a novel therapeutic option in giant cell arteritis. Its differential role in different subgroups, timing of tocilizumab therapy and optimal treatment duration remain to be determined.

Glucocorticoid‐induced diabetes among people without diabetes: a literature review

AbstractThe effect of glucocorticoid on glycaemic control in people with diabetes has been studied extensively in the literature. However, data regarding its effect on glucose homeostasis in those without diabetes are sparse. This review aims to investigate the incidence of glucocorticoid‐induced diabetes among people without diabetes subjected to high‐dose glucocorticoid, to determine its associated risk factors and to examine the effect of high‐dose glucocorticoid on glucose homeostasis.Four databases (Ovid Medline, Scopus, Embase, and PubMed) were searched until August 2017 using the following MeSH terms: ‘glucocorticoid*’, ‘dexamethasone’, ‘diabetes mellitus’ and ‘incidence’. Only studies that included the use of high‐dose glucocorticoid (equivalent to 4 mg dexamethasone per day) for at least seven days in their methodology were included.Nine out of 302 identified studies were included in this review. The incidence of glucocorticoid‐induced diabetes ranged from 1–50%. Pre‐diabetes, age, cumulative dose of glucocorticoid and family history of diabetes were predictors of glucocorticoid‐induced diabetes. The use of high‐dose glucocorticoid aggravated insulin resistance.Most of the studies were retrospective, and used low‐dose glucocorticoid with a short follow‐up period. The incidence of glucocorticoid‐induced diabetes reported varies widely depending on the type, dose and duration of glucocorticoid, the underlying condition and the presence of established risk factors for diabetes. Further prospective studies testing the effect of glucocorticoid in those without pre‐existing risk factors are required to accurately estimate the incidence of glucocorticoid‐induced diabetes. Copyright © 2018 John Wiley &amp; Sons.

Increased visceral adipose tissue and altered adiposity distribution in premenopausal lupus patients: correlation with cardiovascular risk factors.

Objective Visceral adipose tissue (VAT) correlates with cardiovascular risk factors and has never been assessed in systemic lupus erythematosus (SLE). Our aim was to evaluate VAT in premenopausal SLE patients. Methods Sixty-three premenopausal SLE patients and 186 age-matched healthy women were included. Demographic, anthropometric, disease and treatment parameters were evaluated. VAT was measured by dual X-ray absorptiometry (DXA) with APEX 4.0 software. Results SLE patients had a disease duration of 5.25 ± 3.80 years, SLEDAI activity score of 4.35 ± 5.13, SLICC/ACR-DI of 0.70 ± 0.80, current prednisone dose of 11.60 ± 12.10 mg/day and cumulative glucocorticoid dose of 22.34 ± 12.94 g. Overweight/obese SLE patients and controls had similar VAT parameters ( p > 0.05). Among individuals with BMI <25 kg/m2, SLE patients and controls had similar weight, fat mass and fat percentage ( p > 0.05) but patients had higher values of VAT parameters (VAT mass: 260.60 ± 117.23 vs. 194.77 ± 71.42 g, p = 0.001; VAT area: 54.05 ± 24.30 vs. 40.40 ± 14.82 cm2, p = 0.001; VAT volume: 281.75 ± 126.81 vs. 210.61 ± 77.29 cm3, p = 0.001) and trunk/limb fat mass ratio (0.78 ± 0.21 vs. 0.67 ± 0.12, p = 0.002) compared to controls. In SLE, VAT area correlated with weight ( r = 0.66, p < 0.001), non-HDL cholesterol ( r = 0.53, p < 0.001), LDL cholesterol ( r = 0.48, p < 0.001) and triglycerides ( r = 0.33, p = 0.008), but not with disease duration, SLEDAI, SLICC/ACR-DI or current glucocorticoid use ( p > 0.05). Conclusion This study provides original evidence that SLE is associated with increased VAT and altered adiposity distribution. The correlation with traditional risk factors for cardiovascular disease, independent of current glucocorticoid dose and disease activity, suggests the role of visceral fat as an additional tool for risk assessment in these young patients.

Association between glucocorticoid therapy and incidence of diabetes mellitus in polymyalgia rheumatica and giant cell arteritis: a systematic review and meta-analysis

BackgroundPolymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are almost always treated with glucocorticoids (GCs), but long-term GC use is associated with diabetes mellitus (DM). The absolute incidence of this...

Bone mineral density is compromised in very long-term survivors of irradiated childhood brain tumor

Introduction: The increase in the number of childhood brain tumor survivors warrants detailed research to increase our knowledge regarding the possible physical and psychosocial adverse outcomes of tumor and tumor therapy. The aim of this study was to evaluate the current bone health by measuring the bone mineral density (BMD) in irradiated, adult long-term survivors of childhood brain tumors.Material and methods: We studied a national cohort of 74 adult survivors of childhood brain tumors treated with irradiation in Finland between 1970 and 2008. Dual X-ray absorptiometry (DXA) was performed for the femoral necks, total hips, and lumbar spine. Laboratory tests were conducted for evaluating the pituitary, thyroid, and gonadal functions. The participants were interviewed, examined clinically, and the disease and treatment related data were retrieved from the patient files.Results: One fourth of the patients (23.6%) had sex- and age-normalized z-scores below the expected range for age (z-score ≤ −2.0). Mean BMD scores were decreased in all the DXA measurement sites. Male sex was associated with low BMD (p < .05), while body mass index (BMI) had a significant positive association with BMD (p < .01). Mode of irradiation (with or without spinal irradiation) or inclusion of chemotherapy in the treatment did not affect BMD significantly. However, patients with a ventriculoperitoneal shunt had lower BMD than those without a shunt (p < .05). Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were negatively associated with BMD in women (p < .05). However, a higher cumulative dose of glucocorticoids during treatment was not associated with lower BMD, while low BMD was significantly associated with previous fractures in long bones.Discussion: Low BMD should be taken in consideration in treatment of irradiated childhood brain tumor survivors especially in those with previous fractures in long bones.

Trabecular bone score as a supplementary tool for the discrimination of osteoporotic fractures in postmenopausal women with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a risk factor for bone fragility, and its effect on fracture risk is independent of bone mineral density (BMD). The trabecular bone score (TBS) is a new indirect parameter of bone quality. In this study, BMD and the TBS were compared between female postmenopausal RA patients with and those without vertebral fractures (VFs).This study had a cross-sectional design. Two hundred seventy-nine postmenopausal women with RA aged 50 years or older were included in this study. TBS measurements were performed on the same vertebrae as those for the BMD measurements.Among the 279 subjects, 34 had VFs (12.5%). There was a significant difference in the TBS (P = .005) but not L-spine BMD (P = .142) between the subjects with and those without VFs. The odds ratio (OR) for the TBS per standard deviation decrease was significant, even after adjusting for confounding factors such as age, height, rheumatoid factor positivity, the disease activity score for 28 joints (DAS28), the cumulative dose of glucocorticoids (GCs), the time since menopause and osteoporosis drug use (OR = 2.86; 95% CI, 1.34–6.09), and L-spine BMD (OR = 2.57; 95% CI, 1.19–5.54). The TBS was negatively correlated with the cumulative dose of GCs, but not with the DAS28 or erythrocyte sedimentation rate. However, the correlation was an L-shaped nonlinear relationship.The TBS could be a supplementary tool for discriminating osteoporotic fractures in postmenopausal women with RA, and it may have a nonlinear relationship with the cumulative dose of GCs, but not with RA disease activity.

Toxicity risk from glucocorticoids in sarcoidosis patients.

Glucocorticoids (GC) are considered first-line therapy for treating sarcoidosis, but there are few data about the adverse consequences of GC. Although there are several steroid-sparing medications available for treatment, a large proportion of patients are treated with prolonged courses of GC. The toxicities of GC in sarcoidosis populations have not been carefully evaluated. We performed a retrospective cohort study of all newly diagnosed sarcoidosis patients who had the entirety of their medical care in a single health system. We analyzed the time to development of a composite toxicity end-point, including diabetes, hypertension, weight gain, hyperlipidemia, low bone density and ocular complications of GC using Cox proportional hazards analysis. One hundred and five patients were ever treated with GC, whereas 49 were not treated during a median follow-up of 101 months. GC-treated patients developed 1.3±1.1 toxicities during therapy, versus 0.6±1.0 in the non-treated group. After adjustment for age, gender, race and preexisting conditions, the hazard ratio for ever-treated patients was 2.37 (1.34-4.17) for the composite end-point. Age and the presence of preexisting conditions also were associated with reaching the end-point. Similar effects were seen when analyzed for cumulative GC dose and for duration of GC use. For individual end-points, weight gain (HR 2.04) and new hypertension (HR 3.36) were associated with any use of GC. Our data suggest that GC are associated with clinically important toxicities in sarcoidosis patients, associated with both the cumulative dose and duration of treatment.

Relationship between glucocorticoid dose and adverse events in systemic lupus erythematosus: data from a randomized clinical trial

Objective: The aim was to obtain a better understanding of the relationship between exposure to glucocorticoids (GCs) and adverse events (AEs) reported in a randomized controlled trial (RCT) in systemic lupus erythematosus (SLE) patients.Method: We used data from the BLISS-76 trial on belimumab. The data were accessed through an agreement under the SHARE mechanism. AEs were grouped according to medical relevance, i.e. based on similarity of symptoms and pathophysiology. We studied the relationship between AEs and exposure to GCs at baseline and at any time-point, and compared the frequencies of each AE and groups of AEs between tertiles of cumulative GC dose.Results: In total, 991 AEs were reported in the 819 patients of the trial. The frequencies of anaemia, pyrexia, oral herpes, and malaise were significantly higher (p < 0.05) in patients who were on GCs at baseline than in those who were not. The frequencies of several other AEs, including nausea, seasonal allergy, bacterial sinusitis, and viral upper respiratory infection, were significantly higher in patients without GCs. For cumulative GCs, tachycardia and proteinuria were significantly more frequent in the highest tertile than in the lowest tertile, but other AEs and groups of AEs were significantly more frequent in the lowest tertile.Conclusion: This study highlights the feasibility of post-hoc analyses of RCTs using the SHARE mechanism and demonstrates the association of GCs with various AEs. Contrary to expectations, there were also associations between lower cumulative GC dose and several other AEs.

Body composition and adipokines plasma levels in patients with myasthenia gravis treated with high cumulative glucocorticoid dose

This study aimed to evaluate changes in body composition, i.e. overweight, obesity, fat accumulation and low lean body mass and plasma levels of adipokines in patients with MG. The study enrolled 80 patients with MG, and 62 controls. Body fat mass and body lean mass was analyzed by dual-energy X-ray absorptiometry technique (DXA). Plasma levels of leptin were analyzed by Luminex® and adiponectin and resistin were analyzed by ELISA. The mean age of patients with MG was 41.9years, with 13.5years of length of illness, and mean cumulative dose of glucocorticoids 38,123mg. Our results showed that the frequency of obesity is higher in MG patients than in controls, and patients with MG presented higher body fat mass, android body adiposity and total body fat than controls. MG patients presented lower levels of resistin and higher levels of leptin in comparison with controls. There were no differences in the plasma levels of adiponectin. Higher total body fat and lower body lean mass were associated with increased severity of MG symptoms. This result points to the relevance of estimation of body composition in planning long-term care of MG patients.

Glucocorticoids-Induced Hypertension: The Prevalence and Risk Factors

Introduction: Despite benefits in the treatment of most autoimmune and inflammatory diseases, glucocorticoids (GCs) have proved side effects including hypertension, diabetes, osteoporosis and lipid disorders. Determining the risk factors for hypertension can facilitate the identification of high-risk individuals and lead to effective control of the side effects. The present study aimed to determine the risk factors for hypertension in individuals receiving high-dose GCs. Methods: This prospective study recruited 140 adults (age>18 years) requiring prednisolone or equivalent more than 30mg daily for at least three months. The participants’ blood pressure was monitored every month and correlations between the incidence of hypertension and variables such as serum calcium levels, weight, underlying diseases, body mass index (BMI), and folic acid use were investigated by repeated measure analysis. Results: While none of the subjects were hypertensive at baseline, 55 patients (39.28) developed hypertension during the course of the study. Baseline weight and BMI, cumulative GC dose, family history of hypertension, and age were significantly higher in hypertensive patients. Conclusion: High BMI, male gender, elderly, family history of hypertension may have impact on development of hypertension in patients taking GCs.