Efficacy and safety of Chinese herbal medicines combined with cyclophosphamide for connective tissue disease-associated interstitial lung disease: A meta-analysis of randomized controlled trials

This was a meta-analysis of 7 randomized controlled trials conducted in China in patients with connective tissue disease-associated interstitial lung disease, including systemic sclerosis, dermatomyositis/polymyositis, primary Sjogren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus. In the active intervention arms, 260 participants received Chinese herbal medicines plus cyclophosphamide and 246 received cyclophosphamide alone.

Chinese herbal medicines were given as add-on therapy to cyclophosphamide in patients with CTD-ILD, with glucocorticoids used as background treatment in both groups. Across seven trials, the herbal intervention was delivered as 5 decoctions, 1 granule, and 1 oral liquid, with treatment durations of 3 or 6 months; exact doses and frequencies were not reported.

Chinese herbal medicines added to cyclophosphamide improved clinical outcomes and lung function in CTD-ILD compared with cyclophosphamide alone. The combination was associated with better VC (WMD 9.49, 95% CI 5.54 to 13.45), FVC (SMD 0.83, 95% CI 0.36 to 1.29), FEV1 (SMD 0.54, 95% CI 0.23 to 0.86), TLC (SMD 0.90, 95% CI 0.68 to 1.13), DLCO (SMD 1.05, 95% CI 0.38 to 1.73), MVV (SMD 0.83, 95% CI 0.50 to 1.17), HRCT lung integral (SMD -2.02, 95% CI -3.14 to -0.91), and ESR (WMD -13.33, 95% CI -18.58 to -8.09). Clinical efficacy rate was also higher with the combination (RR 1.21, 95% CI 1.09 to 1.35), and adverse events were not increased (4/79 vs 22/77 in 4 studies).

The evidence base was limited by low trial quality, heterogeneity, and small sample sizes within individual studies. All trials were conducted in China, which limits generalizability, and herbal formulations, doses, and time points were not standardized or fully reported.