AB0697 Dramatic reduction of mortality rate by tofacitinib in anti-MDA-5 antibody-positive patients with rapidly progressive interstitial lung disease

Abstract

BackgroundRapidly progressive interstitial lung disease (RP-ILD) is often seen in dermatomyositis patients with anti-melanoma differentiation-associated gene 5 (anti-MDA-5) antibody. They often have a poor prognosis with rapid decline in pulmonary function, leading to respiratory failure (1). Aggressive immunosuppressive therapy has been reported with improved prognosis, however; it may lead to opportunistic infections, including cytomegalovirus (CMV) or Pneumocystis pneumonia (PCP) infection (2, 3).ObjectivesThis study aimed to evaluate the effectiveness of tofacitinib (TOF) in combination with CMV and PCP prophylaxis in anti-MDA-5-positive patients.MethodsMedical records of 17 anti-MDA-5-positive RP-ILD patients enrolled during Mar 2017 to May 2021 were reviewed. RP-ILD was defined by the presence of deteriorated dyspnea, with a decrease in PaO2 levels and emerging radiographic anomalies within 4 weeks without evidence of infection (4). Chest CT was scored using Ichikado score (5). Clinical parameters including ferritin levels, white counts (WBC), Lactate dehydrogenase (LDH) levels, GAP scores (Gender, Age, and Physiology score for idiopathic pulmonary fibrosis) were recorded. Medications included cyclophosphamide (CyP), intravenous immunoglobulin (IVIG), mycophenolic acid derivatives (MPA), rituximab (RTX), and calcineurin inhibitor (CNI). Kaplan-Meier survival analysis and Log-rank test were used to evaluate one-year mortality differences (MedCalc version 19.6). The Ethics Committee approved our study (CE17038B).ResultsSix anti-MDA-5-positive RP-ILD patients were treated with tofacitinib; five had concomitant CMV prophylaxis with valganciclovir (VGCV); 4 had PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP-SMX). Patients’ demographic data are shown in Table 1. The median age, clinical manifestations, laboratory data, and chest CT scores were comparable between tofacitinib and non-tofacitinib groups. Prevalence of MPA use was higher in the non-TOF group. Kaplan-Meier survival analysis (Figure 1) indicated that patients with tofacitinib treatment (p=0.001), valganciclovir (p=0.003), and TMP-SMX (p=0.028) prophylaxis exhibited better 1-year survival rates compared with those without TOF therapy, VGCV, and TMP-SMX prophylaxis.Table 1.Clinical characteristics of anti-MDA-5 antibody-positive patients with RP-ILD receiving tofacitinib vs non-tofacitinib treatment.Tofacitinib (n=6)Non-tofacitinib (n=11)p valueAge (years)58 (42.3-77)57 (50.0-62.0)0.884Female sex, n (%)2 (33.3)6 (54.5)0.620Diabetes mellitus, n (%)0 (0)5 (45.5)0.102Fever, n (%)5 (83.3)10 (90.9)1.000Mechanic’s hands, n (%)4 (66.7)5 (45.5)0.620Ferritin (n=16, ng/ml))2670.9 (719.7-4209.7)1563.5 (967.8-3169.0)0.635WBC (x1000μl)8.7 (6.5-9.9)8.7 (6.0-12.9)0.884LDH (n=16, U/l)367.0 (218.0-557.5)433.0 (331.0-625.3)0.313GAP score5 (2.5-8)5 (2-6)0.808CT score200.0 (124.2-214.2)196.7 (153.3-273.3)0.733TMP-SMX, n (%)4 (66.7)0 (0)0.006**VGCV, n (%)5 (83.3)0 (0)0.001**CyP, n (%)1 (16.7)4 (36.4)0.600IVIG, n (%)1 (16.7)6 (54.5)0.304MPA, n (%)0 (0)7 (63.6)0.035*RTX, n (%)3 (50.0)5 (45.5)1.000CNI, n (%)2 (33.3)6 (54.5)0.620Continuous variables were expressed as median (inter-quartile range).*p<0.05, **p<0.01 by Mann–Whitney U test or Fisher’s Exact test.Figure 1.ConclusionThe study demonstrated the efficacy of tofacitinib treatment in anti-MDA-5-positive RP-ILD. In addition, CMV and PCP prophylaxis appeared to improve in 1-year survival. Rheumatologists might consider TOF with prophylaxis as an option for anti-MDA-5-positive patients in daily practice.