A Retrospective Analysis of Outcome in Melanoma Differentiation–Associated Gene 5–Related Interstitial Lung Disease Treated with Tofacitinib or Tacrolimus

Abstract

Objective The efficacy of tofacitinib in early diagnosis of MDA5-ILD has been described. But whether tofacitinib exposure is associated with a reduced one-year mortality remains undetermined. Methods Patients diagnosed as MDA5-ILD receiving tofacitinib or tacrolimus treatment were included. Cox proportional hazards model adjusted for age, sex, smoking history, anti-MDA5 antibody titers, concurrent use of other steroids sparing agents was performed to compare all-cause mortality and to investigate the risk factors predicting 1-year mortality in the two treatment groups. Results During the study period, twenty-six patients were treated with tofacitinib and thirty-five with tacrolimus. The 6-month and 1-year mortality in tofacitinib group were significantly lower than those in tacrolimus group (38.5% vs. 62.9%, p=0.028; 44.0% vs. 65.7%, p=0.031, respectively). There were thirteen patients diagnosed as rapidly progressive-ILD (RPILD) in tofacitinib group and twenty-two in tacrolimus group. The majority of death occurred in patients with RPILD. The 6-month and 1-year mortality of patients with RPILD in tofacitinib group were also lower than those in tacrolimus group (76.9% and 95.5%, p=0.021; 84.6% and 100.0%, p=0.017). The adjusted model showed tofacitinib exposure was associated with a lower risk for 1-year mortality (HR0.438, 95% CI 0.200-0.960, p=0.039). While the incidence of adverse events and medication discontinuation rates between the two groups were similar (73.1% and 74.3%, p=1.000; 23.1% and 14.3%, p=0.504). Conclusion Our observational study showed tofacitinib use might have a potential impact on improving the outcomes of MDA5-ILD. Future clinical trials are needed to assess the long-term efficacy and tolerability of tofacitinib.

Drs. Dai and Fan reply

“…We thank Wang et al 1 for their interest and suggestions on our study on melanoma differentiation-associated gene 5-related interstitial lung disease (MDA5-ILD), which highlighted that tofacitinib (TOF) use might have a potential effect on improving the outcomes of MDA5-ILD. 2 We completely agree with their valuable suggestions. Indeed, the treatment of MDA5-ILD has always been a huge challenge.…”

The Use of Tofacitinib Has a Potential Effect on Improving the Outcomes of Melanoma Differentiation–Associated Gene 5–Related Interstitial Lung Disease

“…Third, from the data in the article, 1 the mean age in the TAC group was 55.94 (SD 1.72) years compared with 55.42 (SD 2.20) years in the TOF group. Although there was no statistically significant difference in the age of the patients in the 2 groups, the age was generally older.…”

“…Finally, we would like to thank Fan and colleagues again for their contributions 1 to the body of work on this disease and we look forward to hearing from them.…”

“…We read with great interest the recent retrospective analysis by Fan and colleagues on the outcomes of tofacitinib (TOF) or tacrolimus (TAC) in combination with glucocorticoids for melanoma differentiation-associated gene 5 (MDA5)-related interstitial lung disease (MDA5-ILD), published in The Journal of Rheumatology. 1 The authors mainly investigated whether TOF exposure was associated with reduced mortality at 6 months and 1 year, and also compared the incidence of adverse events and discontinuation rates in the TOF and TAC groups for the treatment of MDA5-ILD. Fan et al ultimately concluded that the use of TOF has a potential effect on improving the outcomes of MDA5-ILD.…”

“…[2][3][4] In the study by Fan et al, the composition of anti-MDA5 antibody titers was different between the 2 groups of patients prior to treatment initiation, with 16 (61.5%) in the TOF group having weak-positive antibody titers compared to 9 (25.7%) in the TAC group. 1 Theoretically, this implies that relatively few patients in the TOF group were in an active state of the disease compared to those in the TAC group. Since its interference with the study results could not be excluded, additional subgroup analysis regarding the different antibody titers between the 2 groups of patients was necessary to explain the effect of the different antibody titers on the overall study.…”