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The role of oral methotrexate as a steroid sparing agent in refractory eosinophilic asthma.

ABSTRACT: The use of oral methotrexate for refractory eosinophilic asthma in a tertiary asthma referral centre, Glenfield Hospital, Leicester, was evaluated between January 2006 and December 2014. The patients ( n = 61) were carefully phenotyped at baseline with markers of airway inflammation. In addition, a structured oral methotrexate proforma was utilized to evaluate response to therapy and adverse events. Oral steroid withdrawal was attempted 3 months after commencing treatment. Several outcomes were evaluated at 12 months, including both efficacy and adverse effects; 15% ( n = 9/61) responded by achieving a decrease in daily oral corticosteroid dose (mean 8.43 (±8.76) mg), although we were unable to identify factors that predicted a treatment response. There were no other significant changes in any other clinical outcome measures. There was a high rate of adverse events (19/61 (31%)), primarily gastrointestinal/hepatitis. Our findings support the use of biological agents in preference to using oral methotrexate as a steroid sparing agent at the first instance. In the event of failure of these agents, oral methotrexate remains a therapeutic option, which can be considered in highly specialist severe asthma centres.

SUBMITTER: Bilocca D

PROVIDER: S-EPMC5802657 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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The role of oral methotrexate as a steroid sparing agent in refractory eosinophilic asthma.

Bilocca David D Hargadon B B Pavord I D ID Green R H RH Brightling C E CE Bradding P P Wardlaw A J AJ Martin N N Murphy A C AC Siddiqui S S

Chronic respiratory disease 20170601 1

The use of oral methotrexate for refractory eosinophilic asthma in a tertiary asthma referral centre, Glenfield Hospital, Leicester, was evaluated between January 2006 and December 2014. The patients ( n = 61) were carefully phenotyped at baseline with markers of airway inflammation. In addition, a structured oral methotrexate proforma was utilized to evaluate response to therapy and adverse events. Oral steroid withdrawal was attempted 3 months after commencing treatment. Several outcomes were ...[more]

PMID: 28569072

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Project description:Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources. Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations.We conducted a randomized, double-blind, placebo-controlled, parallel-group study of 61 subjects who had refractory eosinophilic asthma and a history of recurrent severe exacerbations. Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year. The primary outcome measure was the number of severe exacerbations per subject during the 50-week treatment phase. Secondary outcomes included a change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, in which scores range from 1 to 7, with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinically important), forced expiratory volume in 1 second (FEV(1)) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum.Mepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks (2.0 vs. 3.4 mean exacerbations per subject; relative risk, 0.57; 95% confidence interval [CI], 0.32 to 0.92; P=0.02) and with a significant improvement in the score on the AQLQ (mean increase from baseline, 0.55 vs. 0.19; mean difference between groups, 0.35; 95% CI, 0.08 to 0.62; P=0.02). Mepolizumab significantly lowered eosinophil counts in the blood (P<0.001) and sputum (P=0.002). There were no significant differences between the groups with respect to symptoms, FEV(1) after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma.Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma. The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population. (Current Controlled Trials number, ISRCTN75169762.)

Project description:Background:Brain metastases are common in advanced melanoma and often necessitate corticosteroids such as dexamethasone to control symptoms and reduce peritumoral edema. Immunotherapy improves survival in metastatic melanoma, but concomitant treatment with corticosteroids may reduce efficacy. Here, we report the use of bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, as a steroid-sparing agent in melanoma patients with brain metastases treated with immunotherapy. Methods:Medical records and imaging were retrospectively analyzed for melanoma patients with brain metastases who received bevacizumab at our institution between 2012 and 2017. Results:12 melanoma patients with brain metastases received bevacizumab (5-7.5 mg/kg Q2-3 W; median 4 cycles, range 1-9). Patients were BRAF wild-type or resistant to BRAF/MEK inhibitor therapy. All had progressive intracranial disease after prior resection, stereotactic radiosurgery and/or whole brain radiotherapy, and up to four lines of previous systemic treatment. Prior to bevacizumab, all patients had radiologically defined peritumoral edema and nine required dexamethasone for symptom control. In 10 evaluable patients, six reduced their dexamethasone dose by more than 50%, and eight displayed reduced edema 4 weeks after bevacizumab. Seven patients experienced adverse events possibly related to bevacizumab, including intracranial hemorrhage, hypertension, and gastrointestinal bleeding. Ten patients received immunotherapy after bevacizumab. Five patients survived more than 6 months, including one who remained disease-free after 4 years and without neurological deficit despite being hemiplegic from edematous brain metastases prior to bevacizumab. Conclusion:In 12 very poor prognosis melanoma patients with brain metastases, bevacizumab was well-tolerated, associated with improved symptoms and reduced peritumoral edema despite weaning steroids, and facilitated treatment with immunotherapy that provided durable survival in a substantial proportion of cases.

Dataset Information

The role of oral methotrexate as a steroid sparing agent in refractory eosinophilic asthma.

Publications

The role of oral methotrexate as a steroid sparing agent in refractory eosinophilic asthma.

Similar Datasets

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