The efficacy and safety of tacrolimus on top of glucocorticoids in the management of IIM-ILD: a retrospective and prospective study

Objective: To examine the efficacy of tacrolimus on top of glucocorticoids (GCs) in the management of idiopathic inflammatory myopathies-associated interstitial lung disease (IIM-ILD) and further assess the therapeutic benefit and safety of low-dose pirfenidone followed above treatments. Methods: . IIM-ILD patients hospitalized in Tongji Hospital from 2014 to 2020 were included. Demographic data, survival outcomes, and recurrence rates over the 1-year follow-up period were retrospectively analyzed. In the retrospective study, patients were divided into two groups based on treatment with tacrolimus or other conventional immunosuppressants. For the prospective study, a total of 34 IIM-ILD patients either treatment-naïve or after a sufficient period of washout were enrolled from 2018 to 2020 and treated with tacrolimus alone (n=12) or in combination with low-dose pirfenidone (n=22). Clinical characteristics, survival outcomes and multifarious assessment scales were followed up at baseline, 3, 6 and 12 months. The primary endpoint was 12-month survival rate and the secondary endpoints included respiratory-related events, adverse events, exacerbation in HRCT findings and laboratory parameters during therapy courses, and changes in respiratory function. Results: . A total of 250 IIM-ILD patients followed up for over 1 year were identified. Tacrolimus group (n=93) had a significantly higher survival rate (HR=0.428, p=0.018) and a lower relapse rate (HR=0.587, p=0.009) compared with patients with other types of immunosuppressant (n=157) after adjustment. The prospectively enrolled 34 IIM-ILD patients were treated with tacrolimus with or without combination with low-dose pirfenidone. After 12 months of treatment with tacrolimus, patients showed significant improvements in cardio-pulmonary function, disease activity, muscle strength, and mental scale. Sub-group analysis indicated that patients with tacrolimus+pirfenidone combination therapy showed better chest HRCT scores and lower respiratory-related relapse rates than those in tacrolimus only group (log-rank p=0.0029). The incidence rate of drug-associated adverse events (AEs) was comparable between two groups and none of the patients discontinued the treatment due to severe AEs. Conclusion: Tacrolimus is well-tolerated and effective in improving both myositis and lung involvements. Furthermore, low-dose pirfenidone add-on treatment seems could result in multidimensional improvements in IIM-ILD patients. Trial registration. Chinese clinical trial Register, http://www.chictr.org.cn, ChiCTR2100043595.