Background:mycophenolate mofetil (MMF) is currently recommended as a first-line drug for the treatment of interstitial lung disease (ILD) with morphological (chest CT or lung histopathological type) manifestations of nonspecific interstitial pneumonia (NSIP). Rituximab can be used as a salvage treatment for some patients with NSIP ILD who have failed to treat first-line drugs. Methods: A randomized, double-blind, placebo-controlled double-parallel-group clinical trial was conducted in which patients diagnosed with NSIP-type ILD (including connective tissue disease-related ILD and idiopathic NSIP) were randomly assigned to 2 groups for 6 months: the trial group was given MMF (2 g/d) in combination with rituximab (1 000 mg, days 1 and 15), and the control group was given MMF alone. The primary study endpoint was change in FVC as % of the projected value over the 6-month period; Secondary endpoints were 6-month progression-free survival (PFS) and drug safety. Results: A total of 122 patients with NSIP type ILD treated with MMF were included between January 2017 and January 2019, including 63 patients in the trial group (who received at least one rituximab treatment in addition to MMF) and 59 patients in the control group (who received MMF only). After 6 months, compared to the control group, FVC as % of the predicted value was significantly improved from baseline [(1.60 ± 1.13) %vs.（-2.01±1.17）%，95%CI：0.41~6.80，P=0.027 3], with longer PFS (crude hazard ratio of 0.47, 95%CI：0.23~0.96，P=0.03）。 The incidence of serious adverse events was 41% (26/63) in the trial group and 39% (23/59) in the control group; There were 9 infections in the experimental group, including 5 bacterial infections, 3 viral infections and 1 other infections; There were 4 cases of bacterial infection in the control group. Conclusion: For patients with ILD whose morphological manifestations conform to NSIP type, the efficacy of rituximab combined with MMF is better than that of MMF alone; But combination therapy may increase the risk of viral infection.
