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AB0697 (2022)
Dramatic reduction of mortality rate by tofacitinib in anti-MDA-5 antibody-positive patients with rapidly progressive interstitial lung disease
C. W. Tseng1,2, M. Satoh3, Y. M. Chen1,2,4,5,6
1Taichung Veterans General Hospital, Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung, Taiwan, Republic of China
2National Chung Hsing University, Department of Post-Baccalaureate Medicine, College of Medicine, Taichung, Taiwan, Republic of China
3University of Occupational and Environmental Health, Department of Clinical Nursing, School of Health Sciences, Kitakyushu, Fukuoka, Japan
4Taichung Veterans General Hospital, Department of Medical Research, Taichung, Taiwan, Republic of China
5National Chung Hsing University, Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, Taichung, Taiwan, Republic of China
6National Yang Ming Chiao Tung University, School of Medicine, College of Medicine, Taipei, Taiwan, Republic of China

Background: Rapidly 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).


Objectives: This study aimed to evaluate the effectiveness of tofacitinib (TOF) in combination with CMV and PCP prophylaxis in anti-MDA-5-positive patients.


Methods: Medical 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).


Results: Six 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.

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 value
Age (years) 58 (42.3-77) 57 (50.0-62.0) 0.884
Female sex, n (%) 2 (33.3) 6 (54.5) 0.620
Diabetes mellitus, n (%) 0 (0) 5 (45.5) 0.102
Fever, n (%) 5 (83.3) 10 (90.9) 1.000
Mechanic’s hands, n (%) 4 (66.7) 5 (45.5) 0.620
Ferritin (n=16, ng/ml)) 2670.9 (719.7-4209.7) 1563.5 (967.8-3169.0) 0.635
WBC (x1000μl) 8.7 (6.5-9.9) 8.7 (6.0-12.9) 0.884
LDH (n=16, U/l) 367.0 (218.0-557.5) 433.0 (331.0-625.3) 0.313
GAP score 5 (2.5-8) 5 (2-6) 0.808
CT score 200.0 (124.2-214.2) 196.7 (153.3-273.3) 0.733
TMP-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) 0.600
IVIG, n (%) 1 (16.7) 6 (54.5) 0.304
MPA, n (%) 0 (0) 7 (63.6) 0.035*
RTX, n (%) 3 (50.0) 5 (45.5) 1.000
CNI, n (%) 2 (33.3) 6 (54.5) 0.620

Continuous variables were expressed as median (inter-quartile range).

* p <0.05, ** p <0.01 by Mann–Whitney U test or Fisher’s Exact test.


Conclusion: The 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.


REFERENCES:

[1]Sato S, et al. Arthritis Rheum 2009;60(7):2193-200.

[2]Sekiguchi A, et al. J Dermatol 2020;47(8):876-81.

[3]Sabbagh SE, et al. Rheumatology 2021;60(2):829-36.

[4]Kurasawa K, et al. Rheumatology 2018;57(12):2114-19.

[5]Ichikado K, et al. Radiology 2006;238(1):321-9.


Acknowledgements: We are grateful to the Biostatistics Task Force staff of Taichung Veterans General Hospital for their assistance in performing the statistical analyses and Tomoko Hasegawa for her technical assistance with the immunoassays. We also thank Dr. Wen-Nan Huang, Dr. Pin-Kuei Fu, Dr. Chia-Wei Hsieh, Dr. Yi-Hsing Chen, and Dr. Der-Yuan Chen for their help on resources and supervision.


Disclosure of Interests: None declared

Citation: , volume 81, supplement 1, year 2022, page 1476
Session: Scleroderma, myositis and related syndromes (Publication Only)