Journal
BMC MEDICINE
Volume 14, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12916-016-0558-x
Keywords
Idiopathic pulmonary fibrosis; Network meta-analysis; Systematic review; Treatment
Categories
Funding
- Biogen
- Boerhinger Ingelheim
- Gilead Sciences
- Fibrogen
- Kadmon
- MedImmune
- Promedior
- Sanofi-Aventis
- Roche-Genentech
- InterMune-Eu
- UCB celltech
- Veracyte
- Biogen Idec
- Boehringer Ingelheim
- Cipla
- ImmuneWorks
- InterMune
- Roche
- Shionogi
- Takeda
Ask authors/readers for more resources
Background: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with high morbidity and mortality. Effective treatments for IPF are limited. Several recent studies have investigated novel therapeutic agents for IPF, but very few have addressed their comparative benefits and harms. Methods: We performed a Bayesian network meta-analysis (NMA) to assess the effects of different treatments for IPF on mortality and serious adverse events (SAEs). We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) up to August 2015. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach served to assess the certainty in the evidence of direct and indirect estimates. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment. We included parallel group RCTs, including factorial designs, but excluded quasi-randomized and cross-over trials. Studies were only included if they involved adult (>= 18 years of age) patients with IPF as defined by the 2011 criteria and examined one of the 10 interventions of interest (ambrisentan, bosentan, imatinib, macitentan, N-acetylcysteine, nintedanib, pirfenidone, sildenafil, prednisone/azathioprine/N-acetylcysteine triple therapy, and vitamin K antagonist). Results: A total of 19 RCTs (5,694 patients) comparing 10 different interventions with placebo and an average follow-up period of 1 year fulfilled the inclusion criteria. SUCRA analysis suggests nintedanib, pirfenidone, and sildenafil are the three treatments with the highest probability of reducing mortality in IPF. Indirect comparison showed no significant difference in mortality between pirfenidone and nintedanib (NMA OR, 1.05; 95 % CrI, 0.45-2.78, moderate certainty of evidence), pirenidone and sildenafil (NMA OR, 2.26; 95 % CrI, 0.44-13.17, low certainty of evidence), or nintedanib and sildenafil (NMA OR 2.40; 95 % CrI, 0.47-14.66, low certainty of evidence). Sildenafil, pirfenidone, and nintedanib were ranked second, fourth, and sixth out of 10 for SAEs. Conclusion: In the absence of direct comparisons between treatment interventions, this NMA suggests that treatment with nintedanib, pirfenidone, and sildenafil extends survival in patients with IPF. The SAEs of these agents are similar to the other interventions and include mostly dermatologic and gastrointestinal manifestations. Head-to-head comparisons need to confirm these findings.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available