Dataset Information

Adverse events of pirfenidone for the treatment of pulmonary fibrosis: a meta-analysis of randomized controlled trials.

ABSTRACT:

Background

Pirfenidone (PFD) is a novel antifibrotic agent approved for patients with pulmonary fibrosis. However, there are concerns regarding toxicity of the drug. In this meta-analysis, we analyzed the adverse events (AEs) of PFD for the treatment of pulmonary fibrosis.

Methods

We performed a systematic search of PubMed, Embase, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for trials published between January 1999 and October 2011. Data extracted from literature were analyzed with Review manager 5.0.24.

Results

The results of six randomized controlled trials (1073 participants) revealed that the number of individuals who discontinued PFD therapy was significantly higher than patients receiving placebo. The PFD group had a significantly higher rate of gastrointestinal (nausea, dyspepsia, diarrhea, and anorexia), neurological (dizziness and fatigue), and dermatological (photosensitivity and rash) AEs compared to the placebo group.

Conclusions

PFD used for the treatment of pulmonary fibrosis is not so safe or well-tolerated. Notably, gastrointestinal, neurological and dermatological adverse effects were more common in patients receiving PFD therapy, and therefore appropriate precaution is needed.

SUBMITTER: Jiang C

PROVIDER: S-EPMC3467250 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adverse events of pirfenidone for the treatment of pulmonary fibrosis: a meta-analysis of randomized controlled trials.

Jiang Chunguo C Huang Hui H Liu Jia J Wang Yanxun Y Lu Zhiwei Z Xu Zuojun Z

PloS one 20121009 10

<h4>Background</h4>Pirfenidone (PFD) is a novel antifibrotic agent approved for patients with pulmonary fibrosis. However, there are concerns regarding toxicity of the drug. In this meta-analysis, we analyzed the adverse events (AEs) of PFD for the treatment of pulmonary fibrosis.<h4>Methods</h4>We performed a systematic search of PubMed, Embase, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for trials published between January 1999 and October 2011. Data extracted from ...[more]

PMID: 23056564

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Project description:IntroductionThis study assessed baseline cardiovascular (CV) risk factors, concomitant CV medication use, risk of major adverse cardiac events-plus (MACE-plus), and bleeding adverse events (AEs) in patients with idiopathic pulmonary fibrosis (IPF) in three randomized, placebo-controlled phase III trials of pirfenidone.MethodsPatients in the pirfenidone phase III trials were included. Patients with unstable or deteriorating cardiac disease within 6 months before enrollment were ineligible. Medical history at baseline and concomitant CV medication use during treatment were reported. A retrospective, blinded review of AE preferred terms was conducted to identify MACE-plus and bleeding events. Subgroup analyses examined the impact of concomitant CV medication use on how pirfenidone treatment affected clinical outcomes.ResultsIn total, 1247 patients were included [n = 623 pirfenidone (2403 mg/day) and n = 624 placebo]. The median age was 68 years, 74% were male, and 65% were current/former smokers. Commonly reported CV risk factors included hypertension (52%), obesity (44%), hypercholesterolemia (23%), and hyperlipidemia (23%). Pre-existing cardiac disorders included coronary artery disease (16%), myocardial infarction (5%), and atrial fibrillation (5%). Lipid-modifying agents (60%), antithrombotic agents (54%), and renin-angiotensin inhibitors (39%) were commonly used concomitant CV medications. The incidences of MACE-plus and bleeding events were similar between the pirfenidone and placebo groups (1.8% and 2.9% for MACE-plus events and 3.7% and 4.3% for bleeding events, respectively). Except for patients receiving heparin, pirfenidone had a beneficial effect compared with placebo on efficacy outcomes regardless of concomitant CV medications.ConclusionsCV risk factors and comorbidities and use of concomitant CV medications are common in patients with IPF. Pirfenidone did not appear to increase the risk of CV or bleeding events. Use of several concomitant CV medications, including warfarin, did not appear to adversely impact pirfenidone's beneficial effect on efficacy outcomes.Trial registrationNCT00287716, NCT00287729, and NCT01366209.FundingF. Hoffmann-La Roche Ltd. and Genentech, Inc.

Project description:ObjectiveTo systematically evaluate the safety and adverse event profiles of immune checkpoint inhibitors (ICIs) in patients with esophageal cancer (EPC) or gastroesophageal junction cancer (GEJC).MethodsPubMed, Web of Science, Cochrane Library, and major conference proceedings were systematically searched for all phase II or phase III randomized controlled trials (RCTs) in EPC or GEJC using ICIs. Safety outcomes including treatment-related adverse events (trAEs), immune-related adverse events (irAEs), and serious trAEs were evaluated by network meta-analysis or dichotomous meta-analysis based on the random-effects model.ResultsEleven RCTs involving EPC (five RCTs) and GEJC (six RCTs) were included in the final meta-analysis. NMA showed that placebo was associated with the best safety ranking for grade 3-5 trAEs (SUCRA = 96.0%), followed by avelumab (78.6%), nivolumab (73.9%), ipilimumab (57.0%), and pembrolizumab (56.6%). Conventional pairwise meta-analysis (CPM) showed that ICIs have similar grade 3-5 trAE risk compared with chemotherapy (RR = 0.764, 95% CI: 0.574 to 1.016, I 2 = 95.7%, Z = 1.85, P = 0.065). NMA showed that the general safety of grade 3-5 irAEs ranked from high to low is as follows: ChT (85.1%), placebo (76.5%), ipilimumab (56.0%), nivolumab (48.5%), avelumab (48.4%), camrelizumab (41.8%), pembrolizumab (36.4%), and nivolumab + ipilimumab (21.6%). CPM showed that the rates of grade 3-5 irAEs in the ICI group and the chemotherapy group were 7.35% (154/2,095, 95% CI: [6.23%, 8.47%]) versus 2.25% (42/1,869, 95% CI: [1.58%, 2.92%]), with statistical significance (RR = 3.151, 95% CI = 2.175 to 4.563, Z = 6.07, P = 0.000). The most common irAEs in the ICI group were skin reaction (15.76%, 95% CI: [13.67%, 17.84%]), followed by hypothyroidism (9.73%, 95% CI: [8.07%, 11.39%]), infusion-related reactions (5.93%, 95% CI: [4.29%, 7.58%]), hepatitis (5.25%, 95% CI: [4.28%, 6.22%]), and pneumonitis (4.45%, 95% CI: [3.5%, 5.4%]).ConclusionDifferent ICIs had different toxicity manifestations and should not be considered as an entity. Compared with chemotherapy, ICIs were more prone to irAEs, but the overall rates remained low and acceptable. For clinicians, it is important to recognize and monitor the adverse events caused by ICIs for patients with EPC or GEJC.

Dataset Information

Adverse events of pirfenidone for the treatment of pulmonary fibrosis: a meta-analysis of randomized controlled trials.

Background

Methods

Results

Conclusions

Publications

Adverse events of pirfenidone for the treatment of pulmonary fibrosis: a meta-analysis of randomized controlled trials.

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