Efficacy of vamorolone in treatment of Duchene muscle dystrophy. A meta-analysis.

Background and aim: Recent studies evaluated the role of vamorolone in treating Duchenne muscular dystrophy (DMD), so we aimed in our Meta-analysis to assess the efficacy of vamorolone in comparison with placebo and corticosteroids for treating DMD patients. Methods: We searched PubMed, Web of Science, Scopus, and Cochrane library databases. We included any randomized control trials and controlled observational studies that investigated the role of vamorolone in treating DMD patients. We used RevMan software, version 5.4. to perform our meta-analysis. Results: After a search of the literature, 4 studies were included in the meta-analysis; the total number of patients included in the study is 277 patients, 125 patients in the vamorolone group, 106 in the glucocorticoids group, and 46 in placebo (steroid naïve) group. The pooled analysis showed a statistically significant association between the vamorolone group and increased TTSTAND velocity, TTRW velocity and TTCLIMB velocity compared with the placebo group (MD = 0.04, 95% CI = 0.02-0.07, p = 0.002), (MD = 0.24, 95% CI = 0.11-0.37, p = 0.0003), and (MD = 0.06, 95% CI = 0.05-0.06, p < 0.00001), respectively. Also, the analysis showed a statistically significant association between vamorolone and increased TTRW velocity and increased Height percentile for age compared with the glucocorticoid group (MD = -0.14, 95% CI = -0.26 to -0.01, p = 0.03) and (MD = 17.82, 95% CI = 3.89-31.75, p = 0.01), respectively. Conclusion: Our study revealed a significant association between vamorolone and increased TTSTAND velocity, TTRW velocity, and TTCLIMB velocity compared with the placebo (steroid naïve), also showed a statistically significant association between increased TTRW velocity and increased Height percentile for age compared with the glucocorticoid that enhances the privilege of vamorolone over glucocorticoid in treating DMD patients. More multicenter randomized studies are needed to support our results.

Functional outcome measures in young, steroid-naïve boys with Duchenne muscular dystrophy.

The purpose of this study was to quantitate motor performance in 196 genetically confirmed steroid-naïve boys with Duchenne muscular dystrophy (DMD), to evaluate the test-retest reliability of measures of motor performance in young DMD boys, and to assess correlations among the different functional outcomes including timed tests. Boys aged 4-7 years were recruited in the FOR-DMD study, a comparative effectiveness study of different steroid regimens in DMD. Eligible boys had to be able to rise from the floor independently and to perform pulmonary function testing consistently. The boys were evaluated with standardized assessments at the screening and baseline visits at 32 sites in 5 countries (US, UK, Canada, Italy, Germany). Assessments included timed rise from floor, timed 10 m walk/run, six-minute walk distance, North Star Ambulatory Assessment (NSAA) and forced vital capacity (FVC). Mean age at baseline was 5.9 years (range 4.1-8.1 years). Test-retest reliability was high for functional assessments, regardless of time lag between assessments (up to 90 days) and for the majority of age groups. Correlations were strong among the functional measures and timed tests, less so with FVC. Physiotherapy measures are reliable in a young, steroid-naïve population and rise from floor velocity appears to be a sensitive measure of strength in this population.

A low exhaled nitric oxide level excludes a short-term benefit from inhaled corticosteroids in suspected asthma: A randomized placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker that reflects IL-4/IL-13 production and therefore represents T2 allergic inflammation. FeNO has previously been used to guide inhaled corticosteroid (ICS) treatment in asthma. The purpose of this study was to determine if a low FeNO (≤27 ppb) could be used to reliably identify patients with symptoms suggestive of asthma who would not benefit from initiating treatment with an ICS. METHODS: A total of 180 steroid-naïve adults with healthcare professional suspected asthma and an FeNO of ≤27 ppb were randomized to receive either 400 mcg of budesonide or placebo daily for 3 months. The primary outcome was the difference in the Asthma Control Questionnaire 7 (ACQ7) between treatment groups and the study was powered to determine equivalence. Secondary outcomes were the difference in FEV1 , Medical Research Council and Leicester Cough Questionnaire scores. RESULTS: One hundred and thirty-four patients (68 budesonide and 66 placebo) completed the study and were included in the analysis. The between-group mean difference in ACQ7 from baseline to the end of the study was -0.25 and the 95% CI around this difference was -0.004 to 0.495 confirming equivalence (p < 0.05). Differences in forced expiratory volume over 1 s and other secondary outcomes were also small and clinically unimportant. CONCLUSION: The results of this study suggest that steroid-naïve patients with symptoms suggestive of asthma and an FeNO ≤ 27 ppb are unlikely to benefit from initiating treatment with an ICS over 3 months. However, further research is recommended to confirm these findings before withholding ICS treatment.

Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. METHODS: We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. RESULTS: The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. CONCLUSIONS: GMA shows effectiveness in inducing remission in UC patients not receiving steroid.

Children with severe acute asthma admitted to Dutch PICUs: A changing landscape.

The number of children requiring pediatric intensive care unit (PICU) admission for severe acute asthma (SAA) around the world has increased. OBJECTIVES: We investigated whether this trend in SAA PICU admissions is present in the Netherlands. METHODS: A multicenter retrospective cohort study across all tertiary care PICUs in the Netherlands. Inclusion criteria were children (2-18 years) hospitalized for SAA between 2003 and 2013. Data included demographic data, asthma diagnosis, treatment, and mortality. RESULTS: In the 11-year study period 590 children (660 admissions) were admitted to a PICU with a threefold increase in the number of admissions per year over time. The severity of SAA seemed unchanged, based on the first blood gas, length of stay and mortality rate (0.6%). More children received highflow nasal cannula (P < 0.001) and fewer children needed invasive ventilation (P < 0.001). In 58% of the patients the maximal intravenous (IV) salbutamol infusion rate during PICU admission was 1 mcg/kg/min. However, the number of patients treated with IV salbutamol in the referring hospitals increased significantly over time (P = 0.005). The proportion of steroid-naïve patients increased from 35% to 54% (P = 0.004), with a significant increase in both age groups (2-4 years [P = 0.026] and 5-17 years [P = 0.036]). CONCLUSIONS: The number of children requiring PICU admission for SAA in the Netherlands has increased. We speculate that this threefold increase is explained by an increasing number of steroid-naïve children, in conjunction with a lowered threshold for PICU admission, possibly caused by earlier use of salbutamol IV in the referring hospitals.

Steroid-sparing strategies in the management of ulcerative colitis: efficacy of leukocytapheresis.

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonpharmacologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is efficacious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treatment of active UC; however, long-term, high doses of corticosteroids usually produce predictable and potentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be minimized. This may be of great benefit to patients because severe side effects of steroids seriously impair health-related quality of life. In this article, we reviewed current evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the management of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-naïve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid-sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, the available data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.