Impact of inhaled ciclesonide on asymptomatic or mild COVID-19: A randomized trial.

The aim of this study was to determine the efficacy and safety of ciclesonide in the treatment of novel coronavirus disease 2019 (COVID-19) as gauged by pneumonia progression. This multi-center, open-label randomized trial was conducted with patients recruited from 22 hospitals across Japan. Participants were patients admitted with mild or asymptomatic COVID-19 without signs of pneumonia on chest X-rays. Asymptomatic participants were diagnosed after identification through contact tracing. Trial participants were randomized to either the ciclesonide or control arm. Participants in the treatment arm were administered 400 µg of ciclesonide three times a day over seven consecutive days. The primary endpoint was exacerbated pneumonia within seven days. Secondary outcomes were changes in clinical findings, laboratory findings, and changes over time in the amount of the viral genome. In the treatment group, 16 patients (39.0%) were classified as having exacerbated pneumonia compared to 9 (18.8%) in the control group. The risk ratio (RR) was 2.08 (95% confidence interval (CI): 1.15-3.75), indicating a worsening of pneumonia in the ciclesonide group. Significant differences were noted in participants with a fever on admission (RR: 2.62, 90% CI: 1.17-5.85, 95% CI: 1.00-6.82) and individuals 60 years of age or older (RR: 8.80, 90% CI: 1.76-44.06, 95% CI: 1.29-59.99). The current results indicated that ciclesonide exacerbates signs of pneumonia on images in individuals with mild or asymptomatic symptoms of COVID-19 without worsening clinical symptoms.

Deflazacort dose optimization and safety evaluation in Duchenne muscular dystrophy (DOSE): A randomized, double-blind non-inferiority trial.

BACKGROUND: US food and drug administration has recently approved deflazacort for Duchenne muscular dystrophy (DMD) and recommended the dosage of 0.9 mg/kg/d for patients aged ≥5years. However, data assessing the minimal efficacious dose and need of dose-titration based on age or disease severity is limited. OBJECTIVE: To determine whether deflazacort 0.45 mg/kg/d (proposed lower dosage) is non-inferior to 0.9 mg/kg/d among newly diagnosed patients with DMD. METHOD: A double-blinded, non-inferiority, randomized trial, conducted between December 2018 and July 2020. Newly diagnosed patient aged 5-15 years with genetic or muscle biopsy confirmed DMD and baseline 6-min walk distance (6MWD) > 150 m were screened. Patients were randomly assigned (1:1), stratified to prespecified subgroups by age (≤7years and >7years), and baseline 6MWD (≤350 m and >350 m), to receive either 0.45 mg/kg/d or 0.9 mg/kg/d regimens. The primary endpoint was the change in 6MWD, from baseline to week-24 of intervention. The trial was powered with a predefined, non-inferiority margin of 30 m. The analyses were by modified intention-to-treat (mITT). RESULT: A total of 97 patients were enrolled, 40 receiving 0.45 mg/kg/d and 45 receiving 0.9 mg/kg/d deflazacort comprised of mITT population. For primary endpoint analysis the mean (SD) change in 6MWD from baseline to week-24 was 9.7 m (41.5) in deflazacort 0.45 mg/kg/d, and 34.7 m (43.5) for 0.9 mg/kg/d. The mean difference in change in 6MWD across the group was 24.8 m (95% CI 6.7 to 43, p value 0.008). The mean difference in change in 6MWD in the subgroups of boys ≤7 years of age was 21.8 m (95% CI -0.82, 44.5, p = 0.059), with baseline 6MWD of >350 m was 19.9 m (95% CI -2.4, 42.4; p = 0.08). The incidence of combined moderate to severe treatment-related adverse events was significant in the 0.9 mg/kg/d group by week 24 (odds ratio 0.36 [95% CI, 0.14 to 0.89], p = 0.03). DISCUSSION: The efficacy of proposed low dose deflazacort in comparison to the standard dose did not meet the prespecified criteria for non-inferiority. The low dose deflazacort was non-inferior in subgroup of patients with age ≤7 years and baseline 6MWD of >350 m. TRIAL REGISTRATION: Clinical Trial Registry-India Identifier: CTRI/2019/02/017388.

Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial.

Importance: Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen and dosage. Objective: To compare efficacy and adverse effects of the 3 most frequently prescribed corticosteroid regimens in boys with Duchenne muscular dystrophy. Design, Setting, and Participants: Double-blind, parallel-group randomized clinical trial including 196 boys aged 4 to 7 years with Duchenne muscular dystrophy who had not previously been treated with corticosteroids; enrollment occurred between January 30, 2013, and September 17, 2016, at 32 clinic sites in 5 countries. The boys were assessed for 3 years (last participant visit on October 16, 2019). Interventions: Participants were randomized to daily prednisone (0.75 mg/kg) (n = 65), daily deflazacort (0.90 mg/kg) (n = 65), or intermittent prednisone (0.75 mg/kg for 10 days on and then 10 days off) (n = 66). Main Outcomes and Measures: The global primary outcome comprised 3 end points: rise from the floor velocity (in rise/seconds), forced vital capacity (in liters), and participant or parent global satisfaction with treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM; score range, 0 to 100), each averaged across all study visits after baseline. Pairwise group comparisons used a Bonferroni-adjusted significance level of .017. Results: Among the 196 boys randomized (mean age, 5.8 years [SD, 1.0 years]), 164 (84%) completed the trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P < .001 for daily prednisone vs intermittent prednisone using a global test; P = .017 for daily deflazacort vs intermittent prednisone using a global test) and the daily regimens did not differ significantly (P = .38 for daily prednisone vs daily deflazacort using a global test). The between-group differences were principally attributable to rise from the floor velocity (0.06 rise/s [98.3% CI, 0.03 to 0.08 rise/s] for daily prednisone vs intermittent prednisone [P = .003]; 0.06 rise/s [98.3% CI, 0.03 to 0.09 rise/s] for daily deflazacort vs intermittent prednisone [P = .017]; and -0.004 rise/s [98.3% CI, -0.03 to 0.02 rise/s] for daily prednisone vs daily deflazacort [P = .75]). The pairwise comparisons for forced vital capacity and TSQM global satisfaction subscale score were not statistically significant. The most common adverse events were abnormal behavior (22 [34%] in the daily prednisone group, 25 [38%] in the daily deflazacort group, and 24 [36%] in the intermittent prednisone group), upper respiratory tract infection (24 [37%], 19 [29%], and 24 [36%], respectively), and vomiting (19 [29%], 17 [26%], and 15 [23%]). Conclusions and Relevance: Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment; there was no significant difference between the 2 daily corticosteroid regimens. The findings support the use of a daily corticosteroid regimen over the intermittent prednisone regimen tested in this study as initial treatment for boys with Duchenne muscular dystrophy. Trial Registration: ClinicalTrials.gov Identifier: NCT01603407.

Safety of ciclesonide in children with asthma: A review of randomized controlled trials.

Background: Parental concerns about the adverse effects of asthma medications can lead to nonadherence and uncontrolled asthma in children. Ciclesonide (CIC) is a prodrug, with low oropharyngeal deposition and bioavailability that may minimize the risk of local and systemic adverse effects. CIC is U.S. Food and Drug Administration approved for asthma in children ages ≥ 12 years. Objective: To summarize safety results from the 13 phase II or III randomized controlled trials conducted in children with asthma during CIC clinical development. Methods: Four 12- to 24-week trials compared the safety of once-daily CIC 40, 80, or 160 µg/day with placebo; four 12-week trials compared the safety of CIC 80 or 160 µg/day with either fluticasone or budesonide; one 12-month trial compared the long-term safety of CIC 40, 80, or 160 µg/day with fluticasone; one 12-month trial compared growth velocity of CIC 40 or 160 µg/day with placebo; and three cross-over trials compared short-term growth velocity and hypothalamic-pituitary-adrenal (HPA) axis effects of CIC 40, 80, or 160 µg/day with placebo or fluticasone. Results: In all, 4399 children were treated with CIC. The incidence of treatment-emergent adverse events (AE) was similar among the CIC doses and between CIC and placebo in short-term studies and between CIC and fluticasone in the long-term safety study. No CIC-related serious AEs were reported in any study. The incidence of treatment-related oral candidiasis was low and similar between CIC (≤0.5%) and placebo (≤0.7%) or active controls (≤0.5%) in the short-term studies. There was no clinically relevant HPA axis suppression or reduction in growth velocity associated with CIC. Conclusion: Data from 13 studies demonstrate that CIC is associated with low rates of oropharyngeal AEs, with no indication of clinically relevant systemic effects in children with asthma. The favorable safety profile and demonstrated improvements in asthma control make CIC an ideal inhaled corticosteroid for the treatment of asthma in children.

Glucocorticoid-Associated Demise of a Patient With Duchenne Muscular Dystrophy.

We describe the clinical deterioration of a 26-yr-old man with Duchenne muscular dystrophy on oral daily high-dose deflazacort. Although this daily regimen was targeted to benefit ambulation and respiration, it resulted in premature death with lethal sequelae from liver failure, decubiti, diabetes mellitus, and morbid obesity. This case illustrates the need for further research weighing risk versus benefit of daily glucocorticoid therapy, specifically deflazacort, in Duchenne muscular dystrophy patients. Thus, curtailment of daily dosing to eliminate dire sequelae in patients living longer into adulthood than ever before is recommended.

A Review of Deflazacort for Patients With Duchenne Muscular Dystrophy.

Objective: The objective of this article is to review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, and formulary considerations of deflazacort. Data Sources: A search of MEDLINE and EMBASE (1946 to December 31, 2019) was conducted using the terms deflazacort and Duchenne muscular dystrophy (DMD). Results were limited to clinical trials, humans, and English. Additional sources and data were obtained from the references of included articles and prescribing information. Study Selection and Data Extraction: All articles published after July 2014 related to pharmacology, pharmacokinetics, efficacy, or safety of the therapy in human subjects were included. Data Synthesis: Deflazacort 0.9 mg/kg/d is a once-daily oral corticosteroid and is the first drug of its class to be Food and Drug Administration (FDA) approved for DMD. Studies with deflazacort show improved functional outcomes, delayed onset of cardiomyopathy, reduction in scoliosis surgery, and improved survival, but these improvements are supported by relatively weak evidence. Relevance to Patient Care and Clinical Practice: This review presents data from studies published after the most recent DMD 2016 treatment guidelines and offers prescribing considerations, including pharmacology, pharmacokinetics, adverse effects, formulary considerations, and areas of uncertainty. Conclusions: Deflazacort presents an additional, FDA-approved corticosteroid option for patients that offers improved quality of life for DMD patients. However, there is weak evidence to support these benefits; a full risk-benefit analysis considering adverse events, efficacy, cost, and previous trials of steroid therapy is necessary when selecting therapy. Further research will help clarify deflazacort's optimal dose, duration of treatment, and impact on quality of life.

Repurposing of FDA-Approved Drugs for Treating Iatrogenic Botulism: A Paired 3D-QSAR/Docking Approach†.

Botulinum neurotoxin (BoNT) is widely used for the treatment of spasticity, focal dystonia, chronic migraine, facial hemispasm, and facial aesthetic treatments. Generally, treatment with botulinum toxin is a safe procedure when conducted by clinicians with expertise, and local side effects are rare and transient. However, occasionally adverse effects can occur due to the spread of the drug to nontargeted muscles and organs, producing dry mouth, fatigue, and flu-like symptoms, up to signs of systemic botulism, which appears to be more frequent in children treated for spasticity than in adults. In silico 3D-QSAR and molecular docking studies were performed to build a structure-based model on selected potent known botulinum neurotoxin type A inhibitors; this was used to screen the US Food and Drug Administration (FDA) database. Thirty molecules were identified as possible light-chain BoNT/A inhibitors. In this study, we applied a well-established ligand- and structure-based methodology for the identification of hit compounds among a database of FDA-approved drugs. The identification of budesonide, protirelin, and ciclesonide followed by other compounds can be considered a starting point for investigations of selected compounds that could bypass much of the time and costs involved in the drug approval process.

Comprehensive overview of the recently FDA-approved contraceptive vaginal ring releasing segesterone acetate and ethinylestradiol: A new year-long, patient controlled, reversible birth control method.

Introduction: This is an overview of the recently FDA-approved silicone elastomer combined hormonal contraceptive vaginal ring (CVR), which is used cyclically for up to 1 year, eliminating resupply challenges. This ring requires no refrigeration, simplifying the supply chain. Developed by the Population Council, this CVR will soon be marketed in the United States as Annovera™ by TherapeuticsMD. Areas Covered: The composition of the elastomer ring and the chemical, pharmacokinetic and pharmacodynamic properties of both hormonal components are discussed. Results of the clinical trials of its efficacy, tolerability, safety, and acceptability follow. Finally, subanalyses from the clinical trials are presented to guide clinicians in counseling potential users. Expert Opinion: This CVR introduces a new progestin - segesterone acetate (SA) - that has no androgenic or estrogenic action in vitro or in vivo, but has the highest anti-ovulatory potential of all available progestins. SA is paired with EE in an intravaginal elastomer ring, that is used cyclically (21 days in place/7 days removed) to provide 12 months (13 cycles) of contraception. This once-a-month, self-applied CVR offers a convenient, rapidly reversible, year-long contraception with efficacy and side effect profiles similar to other combined hormonal methods, for women with BMI < 29 kg/m2.

Bleeding profile associated with 1-year use of the segesterone acetate/ethinyl estradiol contraceptive vaginal system: pooled analysis from Phase 3 trials.

OBJECTIVES: To describe bleeding patterns among users of the segesterone acetate (SA) and ethinyl estradiol (EE) contraceptive vaginal system (CVS), and identify factors associated with unscheduled bleeding/spotting (B/S). STUDY DESIGN: We pooled results from two multicenter, single-arm, open-label, pivotal, phase 3 studies of the SA/EE CVS conducted in 17 US and 7 international sites. Participants (age 18-40 years; BMI ≤29 kg/m2) followed a 21/7-day in/out schedule of CVS use for up to 13 cycles and recorded vaginal bleeding daily in paper diaries. Scheduled and unscheduled B/S were summarized by cycle. We used multiple logistic regression to identify factors associated with unscheduled bleeding/spotting, based on the first 4 cycles only. RESULTS: Analysis included data from 2070 participants (16,408 cycles). Ninety-eight percent documented scheduled B/S [mean (SD): 4.9 (1.1) days/cycle)]. Absence of scheduled B/S was 5-8% of women/cycle. Unscheduled B/S ranged from 13.2% to 21.7% of women per cycle. Few women (1.8%) discontinued prematurely due to unacceptable bleeding. Black women were more likely to report unscheduled B/S than White women [Adjusted odds ratio (AOR) = 1.49, 95% confidence interval (CI) = 1.14-1.94]. Women with fewer years of schooling [

Eficacia del corticoide intratimpánico como tratamiento de rescate en sordera súbita neurosensorial idiopática / Efficacy of intratympanic corticosteroid as a salvage treatment in idiopathic sudden sensorineural hearing loss

Introducción: La hipoacusia súbita neurosensorial idiopática (SSI) es la pérdida de al menos 30 dB de causa desconocida. Dado que la recuperación auditiva en SSI es variable, el rescate con corticoides intratimpánicos (CIT) podría contribuir a la recuperación auditiva. Nuestro objetivo es analizar la respuesta auditiva tras CIT como rescate, en ausencia de recuperación completa tras tratamiento sistémico. Material y método: Realizamos un estudio observacional de cohortes históricas de los 125 casos detectados de SSI entre 2006 y 2014. De ellos, 16 obtuvieron a la semana recuperación completa según los criterios de Siegel. Los 109 casos restantes se analizaron en dos grupos: el que recibió CIT (grupo de tratamiento) y otro que no lo recibió (grupo control). Evaluamos la recuperación auditiva a los 6 meses y a 2 años. Resultados: La media de audición en la audiometría al diagnóstico no tenía diferencias significativas entre los grupos. Al séptimo día del tratamiento sistémico, el PTA obtenido fue de 53,13 dB en el grupo control y de 66,11 dB en el grupo de estudio (p < 0,01). Tras 6 meses, la ganancia en decibelios obtenida tras el tratamiento con CIT de rescate fue de 10,84 dB, y en el grupo control, de 1,13 dB (p < 0,0001). Tras CIT, solo se consiguió la recuperación completa en 10 pacientes. Ningún paciente del grupo control obtuvo recuperación completa. Conclusión: Encontramos que el tratamiento de rescate con CIT en la SSI favorece la mejoría auditiva tras la ausencia de recuperación después de un tratamiento sistémico. Sin embargo, en la mayoría de los pacientes no consigue obtener una recuperación completa según criterios de Siegel

Introduction: Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as an abrupt hearing loss of at least 30dB of unknown cause. The hearing response obtained after intratympanic steroid injection as a salvage treatment after a prior failure of initial systemic steroid treatment was analysed. Material and method: An observational study was performed on 125 cases of ISSHL who were diagnosed from 2006 to 2014. Sixteen achieved complete recovery after one week according to Siegel's criteria. The remaining 109 cases were analysed in two groups: one that received intratympanic corticosteroid salvage therapy (treatment group) and one that did not (control group). The recovery was analysed after 6 months and 2 years of follow-up. Results: The difference between each group at baseline were not statistically significant. After systemic treatment for 7 days, PTA in the control group was 53.13 dB and 66.11 dB in the treatment group (P < .01). After 6 months, the mean PTA improvement was 10.84dB in the treatment group, and 1.13 dB in the control group, a significant difference (P < .0001). Only 10 cases achieved full hearing recovery after intratympanic corticosteroid salvage therapy, none of the patients did so in the control group. Conclusion: Intratympanic corticosteroid rescue for ISSHL acheived hearing improvement for the cases with failure of initial systemic corticosteroid treatment. However, this treatment did not provide complete hearing recovery according to Siegel's criteria in most cases

Effect of deflazacort on pregnancy outcome in kidney transplant patients: should we change the immunosuppressant before conception?

BACKGROUND: Despite the good prognosis in patients with transplant organs, limited evidence is available on how immunosuppressants affect pregnancy. The aim of this study was to determine whether immunosuppressant use affects the pregnancy outcome and to identify whether there is any need to change the immunosuppressant before the patient tries to conceive. METHODS: This retrospective cohort study included women with previous kidney transplantation history who visited the Department of Obstetrics and Gynecology for either infertility or antenatal care between January 2005 and May 2016. A total of 40 cases (36 women) met the inclusion criteria. Statistical analyses were performed using SAS version 9.4. RESULTS: There were no differences in the immunosuppressant regimen between the pregnant and non-pregnant groups (never-pregnant+miscarriage) (P = 0.73). Individual immunosuppressant use was significantly different in terms of pregnancy outcome among the never-pregnant, miscarriage, and clinical pregnancy groups (azathioprine, P = 0.01; deflazacort, P < 0.0001). Only deflazacort use differed significantly between the clinical pregnancy and non-pregnant groups (P = 0.003). After adjusting for factors that may affect pregnancy outcome, deflazacort use remained significantly associated with a decreased odds ratio for clinical pregnancy (P = 0.02). Cox regression analysis also showed that deflazacort use was the only remaining factor that could hinder the success of clinical pregnancy (P = 0.03). CONCLUSIONS: Our study suggests that the type of immunosuppressive regimen may not affect the success of clinical pregnancy. However, deflazacort may decrease the possibility of clinical pregnancy in women with kidney transplant when they try to conceive.

Segesterone acetate/ethinyl estradiol 12-month contraceptive vaginal system safety evaluation.

OBJECTIVES: To evaluate safety outcomes from clinical studies of a 12-month contraceptive vaginal system (CVS) releasing an average of segesterone acetate (SA) 150 mcg and ethinyl estradiol (EE) 13 mcg daily. STUDY DESIGN: We integrated clinical safety data from nine studies in which women used the CVS for 21 consecutive days and removed it for 7 days of each 28-day cycle. Four studies used the final manufactured CVS, including a 1-year pharmacokinetic study, two 1-year phase 3 trials and a second-year treatment extension study. We assessed safety by evaluating adverse events women reported in a daily diary. We also included data from focused safety studies evaluating endometrial biopsies, vaginal microbiology and liver proteins from one of the phase 3 studies. RESULTS: The combined studies included 3052 women; 2308 women [mean age 26.7±5.1 years; mean body mass index (BMI) 24.1±3.7 kg/m2] received the final manufactured CVS, of whom 999 (43.3%) completed 13 cycles of use. Women using the final CVS most commonly reported adverse events of headache (n=601, 26%), nausea (n=420, 18%), vaginal discharge/vulvovaginal mycotic infection (n=242, 10%) and abdominal pain (n=225, 10%). Few (<1.5%) women discontinued for these complaints. Four (0.2%) women experienced venous thromboembolism (VTE), three of whom had risk factors for thrombosis [Factor V Leiden mutation (n=1); BMI>29 kg/m2 (n=2)]. During 21,482 treatment cycles in the phase 3 studies evaluable for expulsion, women reported partial expulsions in 4259 (19.5%) cycles and complete expulsions in 1509 (7%) cycles, most frequently in the initial cycle [499/2050 (24.3%) and 190/2050 (9.3%), respectively]. Safety-focused studies revealed no safety concerns. CONCLUSION: The 1-year SA/EE CVS has an acceptable safety profile. Additional studies are warranted in obese women at higher risk of VTE. IMPLICATIONS: This 1-year contraceptive vaginal system represents a new long-term, user-controlled and procedure-free option with a safety profile similar to other combination hormonal contraceptives. The same precautions currently used for combination hormonal contraceptive prescriptions apply to this new contraceptive vaginal system.

Efficacy of intratympanic corticosteroid as a salvage treatment in idiopathic sudden sensorineural hearing loss. / Eficacia del corticoide intratimpánico como tratamiento de rescate en sordera súbita neurosensorial idiopática.

INTRODUCTION: Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as an abrupt hearing loss of at least 30dB of unknown cause. The hearing response obtained after intratympanic steroid injection as a salvage treatment after a prior failure of initial systemic steroid treatment was analysed. MATERIAL AND METHOD: An observational study was performed on 125 cases of ISSHL who were diagnosed from 2006 to 2014. Sixteen achieved complete recovery after one week according to Siegel's criteria. The remaining 109 cases were analysed in two groups: one that received intratympanic corticosteroid salvage therapy (treatment group) and one that did not (control group). The recovery was analysed after 6 months and 2 years of follow-up. RESULTS: The difference between each group at baseline were not statistically significant. After systemic treatment for 7 days, PTA in the control group was 53.13dB and 66.11dB in the treatment group (P<.01). After 6 months, the mean PTA improvement was 10.84dB in the treatment group, and 1.13dB in the control group, a significant difference (P<.0001). Only 10 cases achieved full hearing recovery after intratympanic corticosteroid salvage therapy, none of the patients did so in the control group. CONCLUSION: Intratympanic corticosteroid rescue for ISSHL acheived hearing improvement for the cases with failure of initial systemic corticosteroid treatment. However, this treatment did not provide complete hearing recovery according to Siegel's criteria in most cases.

Myocarditis in Duchenne Muscular Dystrophy After Changing Steroids.

Importance: Cardiac dysfunction is a leading cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). This case highlights the importance of steroids in treating cardiac complications of DMD and the dangers of discontinuing or switching between steroid classes. Objective: To recognize the presentation of acute myocardial inflammation, or dystrophinitis, in DMD, which presents as myocarditis and to treat the myocardial inflammation and dilated cardiomyopathy associated with DMD through guideline-directed medical therapy, steroids, and serial surveillance for cardiac dysfunction. Design, Setting, and Participant: A case report of an 18-year-old patient with DMD and with steroid withdrawal-induced myocarditis followed up for 3 years to observe for cardiac function recovery and the natural history of cardiomyopathy in DMD, who was hospitalized in the cardiac care unit and followed up between November 3, 2016, and March 27, 2017. Exposures: Switching from deflazacort to underdosed prednisone for 7 days. Main Outcomes and Measures: Increased myocardial inflammation, edema, and fibrosis after stopping deflazacort abruptly. Results: An 18-year-old male patient with DMD presented to the emergency department with acute-onset chest pain. Ischemic changes were present on electrocardiogram, and elevated cardiac enzymes were detected. Depressed cardiac function and potential evidence of inflammation were seen on cardiac magnetic resonance (CMR) imaging, characterized by elevated T2 values and late gadolinium enhancement. These findings were all consistent with acute myocarditis but without a viral prodrome. Several days prior to presentation, the patient's deflazacort was abruptly discontinued and converted to an equivalent dose of prednisone. After restarting deflazacort, his symptoms improved, and subsequent CMR showed resolution of myocardial edema and improved left ventricular function. Conclusions and Relevance: This case highlights adverse effects associated with changing between corticosteroid classes in DMD cardiomyopathy and also demonstrates the utility of CMR in detecting myocardial inflammation and monitoring response to treatment.

Cataract development associated with long-term glucocorticoid therapy in Duchenne muscular dystrophy patients.

PURPOSE: To evaluate the development of cataracts or elevated intraocular pressure (IOP) in patients with Duchenne muscular dystrophy (DMD) on long-term glucocorticoid (GC) treatment. METHODS: The medical records of DMD patients evaluated from 2010 to 2015 at a single center were reviewed retrospectively. The main outcome measures were prevalence of cataracts and elevated IOP, age of first detection of cataract, time from initial steroid use to first detection of cataract, and relative risk of cataract development for deflazacort versus prednisone treatment. RESULTS: Of 596 DMD patients, 514 underwent GC therapy; all but one was male. The racial distribution was 82.1% white, 1.0% African American, 5.0% Hispanic, 2.9% Asian, and 8.0% more than one race or "other." The prevalence of cataracts was 22.4% in patients on GC therapy. The mean age at which cataract formation was first documented was 12.9 ± 4.1 years (IQR, 9.6-14.6). The mean time from initial steroid use to the first detection of cataract was 6.5 ± 3.6 years (IQR, 4.0-8.6). The odds of cataract development were 2.4-fold higher for patients on deflazacort compared with prednisone (95% CI, 1.3-4.5; P = 0.004). Only 7 patients (1.4%) underwent cataract surgery, at a mean age of 16.9 years (range, 10.7-24.6 years); all were on deflazacort. Among patients with available intraocular pressure measurements, elevated IOP occurred in only 1 patient (1.1%), who was on deflazacort. CONCLUSIONS: In patients undergoing GC therapy for DMD, the rate of cataract formation was slow and well tolerated, with a higher risk among deflazacort patients. The percentage of patients requiring cataract extraction or with elevated IOP was very small. These findings suggest that a schedule of annual eye examinations is appropriate.