Use Of Steroid-sparing Agents Research Articles

An Evidence-Based Approach to Diagnosing Patients Presenting With Orbital Inflammatory Syndromes (An American Ophthalmological Society Thesis)

PurposeThe initial management of patients presenting with orbital inflammatory syndromes (OIS) varies – with some pursuing a diagnostic workup while others treat without any testing. The evidence behind this rationale is limited. A review of patients with orbital inflammation is performed with analysis of diagnostic testing to develop a workflow for such patients. DesignA retrospective review of patients presenting with acute orbital inflammation at a single institution from 2011 – 2020 was conducted. MethodsOrbital imaging was required for inclusion. Patients with high suspicion of neoplasm, bacterial infection, vascular malformation, or thyroid eye disease were excluded. Review of presenting clinical findings, laboratory workup, orbital imaging, and biopsy were performed. Statistical analysis was performed identifying statistically significant diagnostic and treatment maneuvers. ResultsIn total, 172 patients met inclusion criteria (66% female, mean age 46 years). The primary clinical presentation was myositis, dacryoadenitis, and infiltrative in 67, 73, and 32 patients (39.0, 43.0, 18.6%, respectively). Laboratory studies were conducted in 145 (84%) while biopsy was performed in 55 (32%). Specific orbital inflammation (SOI) was diagnosed in 29 (16.9%) with most frequent diagnoses being sarcoidosis, IgG4-related disease, inflammatory bowel disease, and systemic lupus erythematosus. The majority (147, 85.5%) was initially treated with steroids, but steroid-sparing agent use was statistically higher in patients with SOI. ConclusionsIn patients presenting with OIS, distinguishing myositis, dacryoadenitis, and infiltrative disease has workup and differential diagnosis impacts. Because SOI is relatively common, sequelae of SOI, and potential steroid-sparing therapy needs, diagnosis via an evidence-based systemic approach is critical.

Treatment of Polymyalgia Rheumatica by Rheumatology Providers: Analysis from the American College of Rheumatology RISE Registry.

This study describes the demographics, comorbidities, and treatment patterns in a national cohort of patients with polymyalgia rheumatica (PMR) who received care from rheumatology providers. Patients with PMR were identified in the American College of Rheumatology Rheumatology Informatics System for Effectiveness registry from 2016 to 2022. Use of glucocorticoids and immunomodulatory antirheumatic medications used as steroid-sparing agents were examined overall and in a subgroup of patients new to rheumatology practices, the majority with presumed new-onset PMR. In these new patients, multivariate logistic regressions were performed to identify factors associated with persistent glucocorticoid and steroid-sparing agent use at 12 to 24 months. A total of 26,102 patients with PMR were identified, of which 16,703 new patients were included in the main analysis. Patients were predominantly female (55.8%) and White (46.7%), with a mean age of 72.0 years. Hypertension (81.2%), congestive heart failure (52.4%), hyperlipidemia (41.3%), and ischemic heart disease (36.0%) were the most prevalent comorbidities. At baseline, 92.3% of patients were on glucocorticoids, and only 13.1% were on a steroid-sparing agent. At 12 to 24 months, most patients remained on glucocorticoids (63.8%). Although there was an increase in use through follow-up, antirheumatic medications were prescribed only to a minority (39.0%) of patients with PMR. In this large US-based study of patients with PMR receiving rheumatology care, only a minority of patients were prescribed steroid-sparing agents during the first 24 months of follow-up; most patients remained on glucocorticoids past one year. Further identification of patients who would benefit from steroid-sparing agents and the timing of steroid-sparing agent initiation is needed.

Sex Differences in Therapy for Myasthenia Gravis (P7-8.002)

<h3>Objective:</h3> To determine if there are treatment differences between males and females with myasthenia gravis (MG). <h3>Background:</h3> Females with MG report worse quality of life and disease severity scores than males. The reason for these differences remains unclear and may be attributable to differences in treatment. <h3>Design/Methods:</h3> We retrospectively reviewed the medical records of people with generalized MG diagnosed and treated at the University of Calgary between 1997 and 2020. We reviewed disease profile, clinical measures and treatment to determine if there were sex differences. <h3>Results:</h3> We identified 388 patients with MG in our clinic database and included 180 people (41.7% female). There were no sex differences in age at symptom onset and diagnosis, comorbidities or antibody status. Myasthenia Gravis Impairment Index (at 1 year; female 20.9 [95%CI=18.1–23.7] vs male 13.9 [12.0–15.9]) and Myasthenia Gravis Quality of Life scores (at 1 year; female 10.1 [95%CI=8.6–11.5] vs male 6.5 [95%CI=5.2–7.8]) were higher in females, suggesting more impairment and dissatisfaction, while Quantitative Myasthenia Gravis score and Myasthenia Gravis Foundation of America clinical classification were similar between sexes. Females were treated with low dose prednisone (&lt;40mg by mouth daily) less frequently than males (68.0% vs 81.9%, <i>p</i>=0.04), however there was no sex difference in the rate of high dose prednisone use (≥ 40 mg by mouth daily; 45.3% vs 47.6%, <i>p</i>=0.88). There was a non-significant trend towards lower rates of steroid-sparing agent use in females (56.0% vs 65.7%, <i>p</i>=0.21). A higher proportion of females were treated with rituximab (24.0% vs 12.4%, <i>p</i>=0.05). <h3>Conclusions:</h3> Females with MG are less likely to be treated with low dose prednisone and more likely to be treated with rituximab than males. Sex differences in treatment approaches may contribute to disparity in disease outcome and QoL measures. <b>Disclosure:</b> Dr. Beland has nothing to disclose. Dr. Jewett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx Pharmaceuticals. Dr. Jewett has received research support from ALS Canada. Dr. Jewett has received research support from Canadian Institute of Health Research. Dr. Lee has nothing to disclose. Dr. Perera has nothing to disclose. Dr. Korngut has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Korngut has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Korngut has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche.

Sex and Race Differences in Cardiac Sarcoidosis Presentation, Treatment and Outcomes

Although sex- and race-based patterns have been described in the extracardiac organ involvement of sarcoidosis, cardiac sarcoidosis (CS)-specific studies are lacking. We studied CS presentation, treatment and outcomes based on sex and race in a tertiary-center cohort. Multivariable adjusted Cox proportional hazards and survival analyses were performed for primary composite outcomes (left ventricular assist device, heart transplantation, all-cause death) and for secondary outcomes (ventricular arrhythmia and all-cause death. We identified 252 patients with CS (108 female, 109 Black). At presentation with CS, females vs males (P = 0.001) and Black vs White individuals (P = 0.001) more commonly had symptomatic heart failure (HF), with HF most common in Black females (ANOVA P < 0.001). Treatment differences included more corticosteroid use (90% vs 79%; P = 0.020), higher 1-year prednisone dosage (13 vs 10 mg; P = 0.003) and less frequent early steroid-sparing agent use in males (29% vs 40%; P = 0.05). Black participants more frequently received a steroid-sparing agent (75% vs 60%; P = 0.023). Composite outcome-free survival did not differ by sex or race. Male sex had an adjusted hazard ratio of 2.34 (95% CI 1.13, 4.80; P = 0.021) for ventricular arrhythmia. CS course may differ by sex and race and may contribute to distinct clinical CS phenotypes.

Role-Specific Curricular Needs for Identification and Management of Immune-Related Adverse Events.

Immune checkpoint inhibitors (ICIs) activate the immune system against cancer and have become standard of care for many cancers. With increased ICI use, their toxicitiesknown as immune-related adverse events (irAEs) are becoming more common, but it is unclear how prepared relevant clinicians feel to diagnose and treat irAEs. The objective of this study was to assess irAE knowledge, confidence, and experience among generalists and oncology clinicians to guide future curricular interventions related to irAEs. A 25-item survey with questions assessing knowledge, experience level, confidence, and resource utilization regarding irAE diagnosis and management was sent to University of Chicago-affiliated(UChicago) internal medicine residents and hospitalists (inpatient irAE management)along with UChicago oncology fellows, attendings, nurse practitioners (NPs), andphysician assistants (PAs) (inpatient and outpatient) as well as Chicago community oncologists (outpatient) in June 2022. Overall response rate was 37% (171/467). Knowledge scores averaged below 70% for all clinicians. "No idea" responses were most common with knowledge questions on steroid-sparing agent use and ICI use for patients with preexisting autoimmune disease. IrAE experience correlated with higher knowledge for oncology attendings (p = 0.015) and hematology/oncology NPs/PAs (p = 0.031). IrAE experience correlated with higher confidence for residents (p = 0.026), oncology fellows (p = 0.047), and hematology/oncology NPs/PAs (p = 0.042). Most commonly utilized resources were colleagues and UpToDate, and most clinicians were very likely to use online resources in the future. Knowledge and confidence gaps exist, and they were somewhat mitigated by experience. Future irAE curricula can fill these needs through online role-specific resources: irAE identification for generalists versus irAE identification and management for oncologists.

CD8 Encephalitis in HIV: A Review of This Emerging Entity.

Encephalitis is a life-threatening neurological condition with multiple causes in the setting of Human Immunodeficiency Virus (HIV). CD8 Encephalitis (CD8E) is a newly recognised condition which can present in an acute manner, with pertinent features including classical radiological findings with an intense brain parenchymal infiltration of CD8+ T cells. This review attempted to clarify the symptomatology, distribution and determinants of this condition, as well as to examine its vast unknowns. A literature review was undertaken in July 2022, utilising the PubMed and Google Scholar databases. Papers published between 2006-2022 were reviewed. Eighteen papers, totalling 57 patients, were found and analysed. Statistical analysis was undertaken using Chi-squared and Wilcoxon rank-sum tests as appropriate, with p < 0.05 deemed significant. In this review, 57 patients were identified, with a female (61%, 34/56) and Black African (70%, 40/57) preponderance. Females were more likely to present with headache (p = 0.006), and headache was more likely to be present in those who died (p = 0.02). There was no statistically significant association between baseline CD4 count (p = 0.079) and viral load (p = 0.72) with disease outcome. Overall, 77% (41/53) of patients had classical imaging findings, including bilateral gadolinium-enhancing punctate and perivascular white matter lesions. However, many patients (23/57) required a brain biopsy as part of their diagnostic workup. Corticosteroid treatment was commonly prescribed in patients (64%, 35/55) and had a mortality benefit, with an overall survival in this group of 71% (p = 0.0008). In those who died, median survival was 5.5 months. In rare instances, recurrence of the disease was noted, which responded poorly to treatment. CD8E represents a new and complex condition with few risk factors identified for its occurrence. The presenting symptoms are broad, but headache appears to be more common in females and more significantly associated with death. Though rare, CD8E is likely under-diagnosed, possibly due to overlapping features with other illnesses and lack of physician experience in its recognition and management. Corticosteroids demonstrate a clear mortality benefit, but more studies are required to determine their optimal dosing and duration, as well as the use of steroid-sparing agents. Further reviews should help to better determine the risk factors for the condition, as well as non-invasive biomarkers, to aid in diagnosis and help to predict poor prognosis and disease recurrence.

S2329 Iatrogenic Cushing’s Syndrome in Eosinophilic Esophagitis: A Rare Complication of Swallowed Topical Corticosteroids

Introduction: Topical corticosteroids (TCS) are a first-line treatment for eosinophilic esophagitis (EoE), effective at inducing and maintaining disease remission and well-tolerated with uncommon medication-related adverse events. Despite the theoretical risk of adrenal suppression (AS) with prolonged TCS use, data supporting clinically significant adrenal insufficiency in EoE are lacking and the risk of this rare complication is thought to be low. We present a case of iatrogenic Cushing’s syndrome associated with chronic TCS therapy in EoE and an opportunity for steroid-sparing treatment. Case Description/Methods: A 27-year-old woman with a 7-year history of EoE refractory to proton pump inhibitor, 6-food elimination diet, and swallowed fluticasone (FP) achieved disease remission with high-dose oral viscous budesonide (OVB) 4mg. Rapid recurrence of dysphagia, endoscopic findings, and esophageal eosinophilia occurred with lower OVB doses. After FP use for 5 years and transitioning to OVB for 18 months, she developed cushingoid features including prominent pathologic striae on the abdomen, breasts, and thighs, facial rounding, supraclavicular fullness, central obesity, and a dorsocervical hump. Given known exposure to exogenous steroids, features consistent with iatrogenic Cushing’s syndrome, and assumed hypothalamic-pituitary-adrenal axis (HPAA) suppression, the patient began a taper of OVB and steroid-sparing treatment was initiated with dupilumab 300mg weekly. After tapering OVB to 2mg daily over 2 months, assessment (ACTH, morning cortisol, 24-hour urine cortisol) was normal, consistent with HPAA recovery (Figure). Discussion: Topical steroids such as OVB are commonly used and recommended for long-term management of EoE with rare reports of adrenal insufficiency. As data supporting biochemical AS with TCS use in EoE is limited to observational studies with heterogenous testing for AI and lack of symptom assessment, the risk of clinically relevant AS is likely low. However, our case demonstrates that despite the favorable pharmacokinetics, systemic effects of TCS may be understated, particularly with high compliance and prolonged use of high daily doses. Clinicians should counsel patients on the non-negligible risk of AS when prescribing TCS for EoE, and consider assessment of the adrenal axis or use of steroid-sparing agents in those reliant on chronic TCS for disease control.Figure 1.: Endoscopic evidence of (B) active disease on FP (B) disease remission on OVB 4mg daily; (C) Cushingoid features of abdominal striae and dorsocervical hump.

Comparative efficacy of mycophenolic acid and cyclosporine A in treatment of children with steroid-dependent nephrotic syndrome

BACKGROUND. Steroid-dependent nephrotic syndrome (SDNS) treatment is still an important problem in pediatric nephrology since the proper use of steroid-sparing agents can reduce the frequency of relapses and avoid steroid toxicity. THE AIM of our study was to compare the efficacy of cyclosporine A (CsA) and mycophenolic acid (MPA) in children with SDNS. PATIENTS AND METHODS. We observed 91 children (30 girls, 61 boys) with SDNS in 2015-2020. Age at the disease debut was 3 years [2,1; 5,0]. The age at steroid-sparing therapy debut was 8 years [4,0; 16,0]. All children received standard clinical and laboratory examinations and kidney biopsy. RESULTS: 25 children were treated with CsA, and 66 children were treated with MPA. The steroid-sparing therapy duration was 36 months [29; 44]. The frequency of relapses before the steroid-sparing therapy onset was 1,32 ± 0,62 (0,5; 4,3)/year, during steroid-sparing therapy it became 0,5 ± 0,58 (0; 2)/year (р &lt; 0,05). Relapse rate in the MPA group was 0,36 ± 0,49 (0; 1,76)/year compared to 0,85 ± 0,66 (0; 2)/year in the CsA group (p &lt; 0,05). Withdrawal of prednisolone was achieved in 44 (48,4 %) children. The relapse-free period during steroid-sparing therapy with steroid withdrawal was 25 months [6; 120]. 15 children (16,5 %) showed long–term stable remission with no immunosuppressive therapy. 14 of them were treated with MPA and only one with CsA (χ2=9,7, р = 0,0021). The remission duration was 7-32,9 months. There were no severe side effects of CsA and MPA requiring discontinuation of therapy. CONCLUSION: steroid-sparing therapy of SDNS with CsA and MPA significantly reduces relapse frequency. Relapse risk in patients treated with CsA was significantly higher than with MPA. So, it is justified to prescribe MPA as a first-choice immunosuppressive therapy in patients with SDNS.

Therapeutic trials in difficult to treat steroid sensitive nephrotic syndrome: challenges and future directions.

Steroid sensitive nephrotic syndrome is a common condition in pediatric nephrology, and most children have excellent outcomes. Yet, 50% of children will require steroid-sparing agents due to frequently relapsing disease and may suffer consequences from steroid dependence or use of steroid-sparing agents. Several steroid-sparing therapeutic agents are available with few high quality randomized controlled trials to compare efficacy leading to reliance on observational data for clinical guidance. Reported trials focus on short-term outcomes such as time to first relapse, relapse rates up to 1–2 years of follow-up, and few have studied long-term remission. Trial designs often do not consider inter-individual variability, and differing response to treatments may occur due to heterogeneity in pathogenic mechanisms, and genetic and environmental influences. Strategies are proposed to improve the quantity and quality of trials in steroid sensitive nephrotic syndrome with integration of biomarkers, novel trial designs, and standardized outcomes, especially for long-term remission. Collaborative efforts among international trial networks will help move us toward a shared goal of finding a cure for children with nephrotic syndrome.

Safety and Effectiveness of Mycophenolate Mofetil in Interstitial Lung Diseases: Insights from a Machine Learning Radiographic Model

Introduction: Treatment of interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) often includes systemic corticosteroids. Use of steroid-sparing agents is amenable to avoid potential side effects. Methods: Functional indices and high-resolution computed tomography (HRCT) patterns of patients with non-IPF ILDs receiving mycophenolate mofetil (MMF) with a minimum follow-up of 1 year were analyzed. Two independent radiologists and a machine learning software system (Imbio 1.4.2.) evaluated HRCT patterns. Results: Fifty-five (n = 55) patients were included in the analysis (male: 30 [55%], median age: 65.0 [95% CI: 59.7–70.0], mean forced vital capacity %predicted [FVC %pred.] ± standard deviation [SD]: 69.4 ± 18.3, mean diffusing capacity of lung for carbon monoxide %pred. ± SD: 40.8 ± 14.3, hypersensitivity pneumonitis: 26, connective tissue disease-ILDs [CTD-ILDs]: 22, other ILDs: 7). There was no significant difference in mean FVC %pred. post-6 months (1.59 ± 2.04) and 1 year (−0.39 ± 2.49) of treatment compared to baseline. Radiographic evaluation showed no significant difference between baseline and post-1 year %ground glass opacities (20.0 [95% CI: 14.4–30.0] vs. 20.0 [95% CI: 14.4–25.6]) and %reticulation (5.0 [95% CI: 2.0–15.6] vs. 7.5 [95% CI: 2.0–17.5]). A similar performance between expert radiologists and Imbio software analysis was observed in assessing ground glass opacities (intraclass correlation coefficient [ICC] = 0.73) and reticulation (ICC = 0.88). Fourteen patients (25.5%) reported at least one side effect and 8 patients (14.5%) switched to antifibrotics due to disease progression. Conclusion: Our data suggest that MMF is a safe and effective steroid-sparing agent leading to disease stabilization in a proportion of patients with non-IPF ILDs. Machine learning software systems may exhibit similar performance to specialist radiologists and represent fruitful diagnostic and prognostic tools.

Favorable outcomes with reduced steroid use in juvenile dermatomyositis

BackgroundHigh-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing.MethodsWe retrospectively reviewed the records at a single tertiary-care children’s hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis, and complications from treatment.ResultsOf the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (IQR 3–7.5). Myositis control was achieved in a median of 7.1 months (IQR 0.9–63.4). Cutaneous disease control was achieved in a median of 16.7 months (IQR 4.3–89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (IQR 0.5–1.74). The median duration of steroid treatment was 9.1 months, (IQR 4.7–17.4), while the median duration of any pharmacotherapy was 29.2 months (IQR 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%).ConclusionCurrent accepted treatment paradigms for Juvenile Dermatomyositis include oral glucocorticoids beginning at 2 mg/kg/day and reduced over a prolonged time period. However, our results suggest that treatment using reduced doses and duration with early use of steroid-sparing agents is comparably effective in achieving favorable outcomes in Juvenile Dermatomyositis.

Non-steroidal treatment of cardiac sarcoidosis: A systematic review.

The treatment of active cardiac sarcoidosis (CS) usually involves immunosuppressive therapy, with the goal of preventing inflammation-induced scar formation. In most cases, steroids remain the first-line treatment for CS. However, given the side effect profile of their long-term use, steroid-sparing therapies are increasingly used. There are no published randomized trials of steroid-sparing agents in CS. We sought to do a systematic review to evaluate the current published data on the use of non-steroidal treatments in the management of CS. We searched the Cochrane Library, Ovid Medline, Ovid Embase, PubMed, and Web of Science Core Collection databases from inception of database to August 2020 to identify the effectiveness of biological or synthetic disease-modifying antirheumatic agents (s- and bDMARDs). Secondary objectives include safety profile as well as the change in the average corticosteroid dose after treatment initiation. Twenty-three studies were ultimately selected for inclusion which included a total of 480 cases of CS treated with a range of both s- and bDMARDs. In all included studies, sDMARDs and bDMARDs were studied in combination with steroids or as second or higher-line treatments after therapeutic failure or intolerance to corticosteroid use. Methotrexate (MTX) and infliximab (IFX) were the most common synthetic and biologic DMARDs studied respectively, reported in about 35% of the studies reviewed. The use of steroid-sparing agents was associated with a reduction in the maintenance steroid dose used. In conclusion, steroids will remain as the cornerstone of anti-inflammatory management in patients with CS until trials on the use and safety profile of other immunosuppressive agents are completed and published.

Impact of steroids and steroid-sparing agents on quality of life in children with nephrotic syndrome.

Steroids and/or steroid-sparing medications are commonly used for nephrotic syndrome treatment; however, the impact of these medications on health-related quality of life over time is not well described. Longitudinal cohort is up to 5years where children were assessed with baseline and annual Pediatric Quality of Life Inventory questionnaire. A mixed-effects linear regression determined differences in scores among children receiving steroids and/or steroid-sparing agents for at least 30days compared with those not on medication at 1, 3, 6, and 12months prior to assessment. Among 295 children, 64% were male, with a median age of 3.7 (interquartile range [IQR], 2.7, 5.9) years at diagnosis, and comprised 25% Europeans, 40% South Asians, and 8% East/Southeast Asians. Adjusted HRQOL scores were reduced among children taking steroids and steroid-sparing agents among 705 HRQOL measures (median 2 [IQR, 1,3] per child). Compared to children without medication, steroid and steroid-sparing agent use up to 12months prior to assessment were associated with an overall HRQOL drop of 3.17 (95% confidence interval [CI], - 5.25, - 1.08) and 3.18 (95% CI, - 5.24, - 1.12), respectively, after adjustment. Functioning domain scores were reduced by 4.41 points (95% CI, - 6.57, - 2.25) in children on steroids, whereas fatigue domain scores were reduced by 5.47 points (95% CI, - 9.28, - 1.67) in children on steroid-sparing agents after adjustment. HRQOL is consistently decreased in children receiving steroids and steroid-sparing agents, with differential effects on functioning and fatigue. Counseling families on possible effects of prolonged treatment periods is important in the management of childhood nephrotic syndrome.

Outcomes After Transcervical Thymectomy for Ocular Myasthenia Gravis: A Retrospective Cohort Study With Inverse Probability Weighting.

The benefit of thymectomy in reducing requirement for corticosteroids, symptom severity, need for immunosuppression, and hospitalization rates in patients with seropositive generalized myasthenia has recently been established. It is unclear whether this benefit applies to patients with myasthenia and purely ocular manifestations (ocular myasthenia gravis [OMG]). We conducted a retrospective single-center cohort study of patients with OMG. Patients were included if their diagnosis was confirmed by acetylcholine receptor or muscle-specific kinase antibodies, abnormal electrophysiology, or a positive edrophonium test and at least 1 year of clinical follow-up. At each visit, the presence and severity of ocular and generalized symptoms was ascertained using a 4-point scale. Prednisone dose, steroid-sparing agent use, and need for intravenous immunoglobulin or plasmapheresis were recorded. The effect of thymectomy on time-weighted prednisone dose and symptom severity score was assessed using linear regression models. To adjust for nonrandomization of thymectomy, we used inverse probability weighting using a propensity score model derived from the prethymectomy observation period for thymectomy patients and a 6-month lead-in period for nonthymectomy patients that incorporated age, sex, acetylcholine receptor antibody seropositivity, disease severity (as defined by both symptom severity and treatment requirement), and treating physician preferences. Eighty-two patients (30 with thymectomy and 52 nonthymectomy) were included. In unadjusted analyses, time-weighted daily prednisone dose was 2.9 mg higher with thymectomy compared with nonthymectomy (95% CI: 0.2-5.7), but after inverse probability weighting, this was no longer statistically significant (difference = 1.7 mg, 95% CI: -0.8 to 4.2). There was no statistically significant difference in symptom severity score (adjusted difference = 0.35, 95% CI: -0.02 to 0.72) or risk of generalization (P = 0.22). In this retrospective study that used statistical techniques to account for nonrandomization, no significant differences in prednisone dose or symptom severity after thymectomy in ocular myasthenia were demonstrated.

Pediatric Ocular Myasthenia Gravis

We present a review of current strategies in the treatment of pediatric ocular myasthenia gravis (OMG). A critical appraisal was performed of the current literature available on OMG and the treatment options available for all age populations. From this data, we present the evidence surrounding therapeutic options for pediatric OMG and discuss treatment outcomes in the pediatric population. We also present gaps in the literature with regard to pediatric OMG and possibilities for future research. While there is data on the use of steroid-sparing immunosuppressive agents for myasthenia gravis (MG), as a whole it is more specific for the use in generalized juvenile myasthenia gravis (JMG) and more focused toward the adult population. In the currently available literature, there have been reports published on the use of steroid-sparing agents including azathioprine, cyclosporine, and mycophenolate mofetil. A recent open-label trial has provided evidence for the use of tacrolimus to improve symptoms of JMG including OMG that were refractory to prednisone. In addition to this, there has been evidence that thymectomy is effective in controlling pediatric OMG and shows a pattern toward preventing generalization of MG, reducing prednisone dosing, and increasing resolution of disease. There are other treatments used in the pediatric population of MG, including intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab, but currently there are no reports on use in OMG. In the population of patients with pediatric OMG, a high percentage of patients are able to obtain stabilization of symptoms using only pyridostigmine or pyridostigmine in combination with oral prednisone. Rates of generalization of OMG range from 15 to 35%, with higher rates in the adolescent population, but approximately 25% of pediatric patients with OMG can have complete remission. For pediatric OMG patients with ophthalmologic manifestations that are refractory to pyridostigmine and prednisone, the use of steroid-sparing agents has been practiced more recently. In addition to this, thymectomy has been utilized in this population. In both of these instances, no pediatric randomized control trials have been performed to date.

Cyclosporine for moderate-to-severe alopecia areata: A double-blind, randomized, placebo-controlled clinical trial of efficacy and safety

Despite widespread use of steroid-sparing agents, particularly cyclosporine, for treatment of alopecia areata (AA), there are no clinical trials investigating the efficacy of these agents. To evaluate the efficacy of cyclosporine compared with placebo at 3months in patients aged 18 to 65years with moderate-to-severe AA. A double-blind, randomized, placebo-controlled trial was conducted. Adults aged 18 to 65years of age with moderate-to-severe AA were randomized in a 1:1 ratio to receive 3months of cyclosporine (4mg/kg/d) or matching placebo. Blinded assessments included physical examination, blood biochemistry, photography, quality of life measurements, and efficacy evaluation using Severity of Alopecia Tool score and eyelash and eyebrow assessment scales. The results obtained for 32 participants (16 who received cyclosporine and 16 who received placebo) were analyzed. Compared with the placebo group, the cyclosporine group had a greater proportion of participants achieving at least a 50% reduction in Severity of Alopecia Tool score (31.3% vs 6.3% [P=.07]) and greater proportion of participants achieving a 1-grade improvement in eyelash (18.8% vs 0% [P=.07]) and eyebrow (31.3% vs 0% [P=.02]) scale score. Small sample size and single-institution trial may limit interpretation and generalizability of these results. Response approached but did not reach a statistically significant difference between cyclosporine and placebo.

Early use of steroid-sparing agents in the inactivation of moderate-to-severe active thyroid eye disease: a step-down approach.

The current first-line treatment for management of active thyroid eye disease (TED) is high-dose intravenous corticosteroids, which have the potential for serious adverse effects. Our aim was to evaluate the effect of steroid-sparing agents (SSAs) in patients with moderate-to-severe active TED, using methotrexate as first-line. Presented is a retrospective, four-year, single-centre, consecutive case series of patients with moderate-to-severe TED treated using the Oxford protocol. Treatment modality, disease activity, and adverse effects are reported at presentation, 6- and 12-month follow-up. 104 consecutive TED patients treated by the Oxford TED team were reviewed. 24 patients with moderate-to-severe active disease were identified (mean age 46.8years;12 female) with a mean pretreatment VISA inflammatory index score of 5.5/10 (SD=1.98; range 1-9). Intravenous methyl-prednisolone (IVMP) and an SSA was commenced in all patients. Mean total steroid dose was 2.72g (SD=1.4;1.0-6.9). 38% of patients (n=9) received ≤1.5g of IVMP. Only two patients required >4.5g of IVMP equating to the EUGOGO treatment protocol dose for this patient group. There was significant improvement in inflammatory index score both at the intermediate review (mean score 2.7; SD=2.8; P<0.001; mean follow up 25.2weeks) and at one year or last follow-up (mean score 1.4; SD=1.5; P<0.001; mean follow up 48.0weeks). No serious or long-term adverse effects were reported. This study suggests that the initiation of an SSA, using methotrexate as first-line, with limited adjuvant IVMP is an effective and safe treatment for moderate-to-severely active TED, resulting in a significant reduction in both disease activity and total steroid load.

Clinical profile of patients with steroid sensitive nephrotic syndrome at tertiary care centre in Gujarat, India

Background: Nephrotic syndrome is a significant cause of chronic renal disease in children. The objective of the study was to analyze demographic profile, response to steroids and associated complications, in children with Nephrotic syndrome.Methods: A retrospective study of all patients referred to Renal diseases clinic at GMERS Medical College Gotri Vadodara was done. Period of study was from year 2014 to June 2017. Variables assessed were sex distribution, age at presentation for first attack, occurrence of complications, steroid responsiveness and use of steroid sparing agents. Study was done from special clinic cards used for documentation of visits of patients in Nephrotic disease special clinic.Results: 59 patients were studied. Mean age at presentation of was 4.08 years. Sex distribution ratio was 1.18:1. 88% of cases were infrequent relapsers. Steroid dependence was observed in 8.4% of cases. Complications were noted in 38% children. UTI was the commonest complication 13.5%. Associated renal conditions were present in 5% of children.Conclusions: In the present study clinical profile of children with Nephrotic syndrome was concordant with typical nephrotic syndrome in children. Pattern of nephrotic syndrome and response to treatment did not differ significantly from other studies.

The Oxford Multidisciplinary Thyroid Eye Disease Clinic: Can short waiting times and use of Steroid Sparing Agents reduce total glucocorticoid dose and requirement for surgery/radiotherapy?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Syndrome néphrotique idiopathique corticodépendant de l’enfant : facteurs prédictifs de recours à un traitement immunosuppresseur

More than half of the children with idiopathic nephrotic syndrome become steroid-dependent (or frequent relapsers) and will later require the use of complementary treatment aiming to reduce steroids' side effects and to limit the number of proteinuria relapses. It appears important to identify these children as early as possible in order to adapt their treatment. The aim of this study was to analyze the population of children, under 18 years of age, diagnosed between 1/01/2000 and 31/05/2015 with an idiopathic nephrotic syndrome and followed at the Montpellier University Hospital to search for criteria predictive of steroid-sparing agent use. In this retrospective study of children with idiopathic nephrotic syndrome, the exclusion criteria were primary steroid resistance and children with no proteinuria relapse after diagnosis. Eighty-four children (54 boys) were included in this study. The mean follow-up duration was 5.5 years (0.75-16). The mean age at diagnosis was 4.6 years. Sixty-five children (77%) received at least one steroid-sparing agent during their follow-up, within a mean 10 months after diagnosis. In these patients, the first relapse of the disease occurred earlier when compared with the children who were maintained on steroid alone (4 months vs 7 months; P<0.001). The use of methylprednisolone pulses to obtain a remission, the cumulative dose of steroid treatment, and the number of proteinuria relapses were also significantly correlated with the use of complementary immunosuppressive therapy. We found no predictive criteria of the use of steroid-sparing agents at diagnosis in our population of children. Nevertheless, with the steroid regimen used, the time within which the first proteinuria relapse occurred appears to be a significant criterion for the secondary use of a steroid-sparing agent. These data should be taken into account when choosing the treatment regimen.