New research sheds light on mycophenolate and azathioprine efficacy in interstitial lung disease
Italy: A systematic review and meta-analysis published in BMJ Open Respiratory Research assess whether the administration of mycophenolate mofetil (MMF) or azathioprine (AZA) in interstitial lung disease (ILD) was associated with changes in pulmonary function and gas transfer.
The researchers reported an unclear benefit of MMF on interstitial lung disease. They found no significant difference in outcome compared with placebo or standard of care.
"We observed a minor increase in percent predicted forced vital capacity and diffusion lung capacity of carbon monoxide from baseline in MMF. Studies on AZA were limited," Francesco Lombardi, Pulmonary Medicine, Policlinico Universitario Agostino Gemelli, Roma, Italy, and colleagues wrote.
Mycophenolate mofetil and azathioprine are two immunomodulatory drugs used for treating connective tissue disease, with both drugs having mechanisms that target lymphocytes. They are being increasingly used to treat ILD, but the evidence is limited for the efficacy of AZA or MMF in improving outcomes. Therefore, Dr. Lombardi and colleagues sought to evaluate the MMF or AZA efficacy on pulmonary function in ILD.
The population included any interstitial lung disease diagnosis, interventions included AZA or MMF treatment, and the outcome was delta change from baseline in percent gas transfer (diffusion lung capacity of carbon monoxide, %DLco) and predicted forced vital capacity (%FVC). The study's primary endpoint compared outcomes relative to the placebo comparator; the secondary endpoint evaluated outcomes in treated groups only.
Prospective observational studies and randomized controlled trials (RCTs) were included. No language restrictions were applied. Studies with high-dose concomitant steroids and retrospective studies were excluded.
A systematic search of online databases was conducted on May 9. Meta-analyses were specified according to drug and outcome with random effects, I2 evaluated heterogeneity, and Grading of Recommendations, Assessment, Development, and Evaluation evaluated certainty of evidence.
Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.
Following were the key findings:
- Out of 2831 publications screened, 12 were suitable for quantitative synthesis.
- Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94; %DLco −2.03).
- An overall 2.03% change from baseline in %FVC was observed in MMF, and the RCT subgroup summary estimated a 4.42% change from baseline in %DLCO.
- AZA studies were limited.
- All estimates were considered very low-certainty evidence.
In conclusion, there were limited RCTs of AZA or MMF, and their benefit on interstitial lung disease was of very low certainty. MMF may support the preservation of pulmonary function, but the confidence in the effect was weak.
"To support high certainty evidence, RCTs should be designed to directly assess the efficacy of mycophenolate mofetil in ILD," the researchers wrote.
Reference:
Lombardi F, Stewart I, Fabbri L REMAP-ILD Consortium, et alMycophenolate and azathioprine efficacy in interstitial lung disease: a systematic review and meta-analysisBMJ Open Respiratory Research 2024;11:e002163. doi: 10.1136/bmjresp-2023-002163
