Journal of Peking University (Health Sciences) ›› 2025, Vol. 57 ›› Issue (6): 1101-1106. doi: 10.19723/j.issn.1671-167X.2025.06.013

Previous Articles     Next Articles

Clinical characteristics, efficacy and safety of antifibrotic agents in elderly patients with connective tissue disease-associated interstitial lung disease

Jingwen LAN, Zhe CHEN, Yongjing CHENG, Like ZHAO*()   

  1. Department of Rheumatology and Immunology, Beijing Hospital; National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
  • Received:2025-08-13 Online:2025-12-18 Published:2025-10-28
  • Contact: Like ZHAO
  • Supported by:
    the National High-Level Hospital Clinical Research Funding(BJ-2025-251); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-001)

RICH HTML

  

Abstract:

Objective: To investigate the clinical characteristics, treatment regimens, and the efficacy and safety of antifibrotic agents in elderly patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods: This single-center retrospective cohort study enrolled 129 elderly patients (≥60 years) with a confirmed diagnosis of CTD-ILD at Beijing Hospital from June 2016 to June 2024. Baseline data, including comorbidities and CTD subtypes, treatment regimens (glucocorticoids, immunosuppressants, antifibrotic agents), pulmonary function parameters, high-resolution computed tomography (HRCT) imaging features, and adverse events were retrieved from the electronic medical record system. Treatment efficacy was evaluated according to the 2022 American Thoracic Society/European Respiratory Society criteria for progressive pulmonary fibrosis. Statistical analyses were performed using SPSS 26.0, with χ2 tests or t-tests applied for between-group comparisons. Results: (1) Clinical characteristics: The predominant CTD subtypes were rheumatoid arthritis (RA), primary Sjögren syndrome (pSS), and polymyositis or dermatomyositis (PM/DM). Hypertension was present in 45.7% of the patients, reflecting the characteristics of multiple comorbidities in the elderly population. (2) CTD treatment regimens: 76.0% of the patients received glucocorticoid therapy, 83.7% used immunosuppressants (IS)/conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), among which cyclophosphamide had the highest usage rate (47.3%); 31.8% of the patients were combined with antifibrotic drugs (nintedanib 16.3%, pirfenidone 10.1%, and 5.4% used both). (3) Efficacy of antifibrotic therapy: There was no statistically significant difference in the 6-month HRCT progression rate between the antifibrotic and non-antifibrotic groups (31.3% vs. 45.2%, P=0.193). However, the proportion of the patients with pulmonary function deterioration in the antifibrotic group was significantly lower than that in the non-antifibrotic group (34.1% vs. 53.4%, P=0.041), suggesting a potential role in delaying pulmonary function deterioration. (4) Safety of antifibrotic agents: Gastrointestinal adverse events occurred in 39.0% of the patients receiving antifibrotics (26.8% diarrhea, 22.0% nausea), and abnormal liver function was observed in 17.1%. (5) Long-term outcomes: During a 2-year follow-up, 67.4% of the patients experienced infections (47.3% pulmonary infections), 14.0% progressed to respiratory failure, and the all-cause mortality rate was 2.3%. Conclusion: The main subtypes of CTD-ILD in the elderly are RA, pSS, and PM/DM, which are often complicated with hypertension. Antifibrotic agents may significantly delay the deterioration of pulmonary function, but attention should be paid to the risks of gastrointestinal adverse effects and hepatotoxicity. Infection remains the primary complication, emphasizing the need to balance benefits of immunosuppressive therapy and the risk of infection to formulate treatment strategies.

Key words: Elderly, Connective tissue disease-associated interstitial lung disease, Antifibrotic agents

CLC Number: 

  • R593.2

Table 1

Baseline characteristics of elderly CTD-ILD patients"

Baseline characteristics Value
Demographic and clinical characteristics
  Female 94 (72.9)
  Male 35 (27.1)
  Smoking history 27 (20.9)
  Age/years 69.69±5.81
  Disease duration/years 10.51±10.11
CTD subtypes
  RA 37 (28.7)
  pSS 30 (23.3)
  PM/DM 28 (21.7)
  SSc 18 (14.0)
  AAV 12 (9.3)
  SLE 4 (3.1)
Common comorbidities
  Hypertension 59 (45.7)
  Diabetes mellitus 29 (22.5)
  Coronary artery disease 28 (21.7)
  Pulmonary neoplasms 3 (2.3)

Table 2

Distribution of CTD targeted therapies in elderly CTD-ILD patients"

Therapeutic classification Value, n (%) Total, n (%)
Glucocorticoids 98 (76.0)
IS/csDRAMDs 108 (83.7)
  CTX 61 (47.3)
  TGT 58 (45.0)
  MTX 36 (27.9)
  LEF 26 (20.2)
  HCQ 21 (16.3)
  MMF 20 (15.5)
  TAC 17 (13.2)
  CsA 4 (3.1)
bDRAMDs 17 (13.2)
  Tocilizumab 8 (6.2)
  Adalimumab 5 (3.9)
  Rituximab 4 (3.1)
tsDRAMDs 22 (17.1)
  Tofacitinib 15 (11.6)
  Baricitinib 7 (5.4)

Table 3

Pulmonary function progression in elderly CTD-ILD patients"

Pulmonary function parameters Non-antifibrotic group (n=88) Antifibrotic group (n=41) χ2 P
FVC% pred decline ≥5% 34 (38.6) 13 (31.7)
DLCO% pred decline ≥10% 25 (28.4) 10 (24.4)
Total 47 (53.4) 14 (34.1) 4.163 0.041

Table 4

Incidence of major adverse events in elderly CTD-ILD patients over a 2-year period"

Adverse event classification Value, n (%) Total, n (%)
Infection 87 (67.4)
  Pulmonary infection 61 (47.3)
  Upper respiratory tract infection 53 (41.1)
  Urinary tract infection 15 (11.6)
  VZV infection 4 (3.1)
Cardiovascular events 15 (11.6)
  Heart failure 9 (7.0)
  Pulmonary hypertension 6 (4.7)
Respiratory failure 18 (14.0)
RP-ILD 7 (5.4)
All-cause mortality 3 (2.3)
1
中国医师协会风湿免疫科医师分会风湿病相关肺血管/间质病学组, 国家风湿病数据中心. 2018中国结缔组织病相关间质性肺病诊断和治疗专家共识[J]. 中华内科杂志, 2018, 57 (8): 558- 565.
2
Mathai SC , Danoff SK . Management of interstitial lung disease associated with connective tissue disease[J]. BMJ, 2016, 352, h6819.
3
Spagnolo P , Cordier JF , Cottin V . Connective tissue diseases, multimorbidity and the ageing lung[J]. Eur Respir J, 2016, 47 (5): 1535- 1558.

doi: 10.1183/13993003.00829-2015
4
Mena-Vázquez N , Redondo-Rodriguez R , Rojas-Gimenez M , et al. Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: A multicenter prospective study[J]. Front Immunol, 2024, 15, 1341321.

doi: 10.3389/fimmu.2024.1341321
5
Pofi R , Caratti G , Ray DW , et al. Treating the side effects of exogenous glucocorticoids; Can we separate the good from the bad?[J]. Endocr Rev, 2023, 44 (6): 975- 1011.

doi: 10.1210/endrev/bnad016
6
Wijsenbeek M , Suzuki A , Maher TM . Interstitial lung diseases[J]. Lancet, 2022, 400 (10354): 769- 786.

doi: 10.1016/S0140-6736(22)01052-2
7
Allanore Y , Vonk MC , Distler O , et al. Continued nintedanib in patients with systemic sclerosis-associated interstitial lung disease: 3-year data from SENSCIS-ON[J]. RMD Open, 2025, 11 (1): e005086.

doi: 10.1136/rmdopen-2024-005086
8
Maher TM , Mayes MD , Kreuter M , et al. Effect of nintedanib on lung function in patients with systemic sclerosis-associated interstitial lung disease: Further analyses of a randomized, double-blind, placebo-controlled trial[J]. Arthritis Rheumatol, 2021, 73 (4): 671- 676.

doi: 10.1002/art.41576
9
Solomon JJ , Danoff SK , Goldberg HJ , et al. The design and rationale of the Trail1 trial: A randomized double-blind phase 2 clinical trial of pirfenidone in rheumatoid arthritis-associated interstitial lung disease[J]. Adv Ther, 2019, 36 (11): 3279- 3287.

doi: 10.1007/s12325-019-01086-2
10
Crestani B , Huggins JT , Kaye M , et al. Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: Results from the open-label extension study, INPULSIS-ON[J]. Lancet Respir Med, 2019, 7 (1): 60- 68.

doi: 10.1016/S2213-2600(18)30339-4
11
Lancaster LH , de Andrade JA , Zibrak JD , et al. Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis[J]. Eur Respir Rev, 2017, 26 (146): 170057.

doi: 10.1183/16000617.0057-2017
12
Jeganathan N , Sathananthan M . Connective tissue disease-related interstitial lung disease: Prevalence, patterns, predictors, prognosis, and treatment[J]. Lung, 2020, 198 (5): 735- 759.

doi: 10.1007/s00408-020-00383-w
13
Aletaha D , Neogi T , Silman AJ , et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League against Rheumatism Collaborative Initiative[J]. Arthritis Rheum, 2010, 62 (9): 2569- 2581.

doi: 10.1002/art.27584
14
Aringer M , Costenbader KH , Dörner T , et al. Response to: "2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus by Aringer et al" by Cui et al[J]. Ann Rheum Dis, 2022, 81 (9): e166.

doi: 10.1136/annrheumdis-2020-218615
15
Lundberg IE , Tjärnlund A , Bottai M , et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups[J]. Arthritis Rheumatol, 2017, 69 (12): 2271- 2282.

doi: 10.1002/art.40320
16
van den Hoogen F , Khanna D , Fransen J , et al. 2013 classification criteria for systemic sclerosis: An American College of Rheumatology/European League against Rheumatism Collaborative Initiative[J]. Arthritis Rheum, 2013, 65 (11): 2737- 2747.

doi: 10.1002/art.38098
17
Lynch DA , Sverzellati N , Travis WD , et al. Diagnostic criteria for idiopathic pulmonary fibrosis: A Fleischner Society White Paper[J]. Lancet Respir Med, 2018, 6 (2): 138- 153.

doi: 10.1016/S2213-2600(17)30433-2
18
王凯, 殷松楼. 结缔组织病相关间质性肺病的诊治进展[J]. 中国免疫学杂志, 2016, 32 (10): 1562- 1565.
19
李梦涛, 王迁. 结缔组织病相关间质性肺病: 从发病机制研究到"双达标"治疗策略[J]. 天津医药, 2024, 52 (7): 673- 678.
20
李爽, 陈宏. 结缔组织病相关性间质性肺病的特征及治疗[J]. 临床肺科杂志, 2020, 25 (9): 1427- 1431.
21
Khanna D , Tashkin DP , Denton CP , et al. Etiology, risk factors, and biomarkers in systemic sclerosis with interstitial lung disease[J]. Am J Respir Crit Care Med, 2020, 201 (6): 650- 660.

doi: 10.1164/rccm.201903-0563CI
22
Wang HF , Wang YY , Li ZY , et al. The prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease: A systematic review and meta-analysis[J]. Ann Med, 2024, 56 (1): 2332406.

doi: 10.1080/07853890.2024.2332406
23
Tashkin DP , Roth MD , Clements PJ , et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS Ⅱ): A randomised controlled, double-blind, parallel group trial[J]. Lancet Respir Med, 2016, 4 (9): 708- 719.

doi: 10.1016/S2213-2600(16)30152-7
24
Ghembaza A , Vautier M , Cacoub P , et al. Risk factors and prevention of Pneumocystis jirovecii pneumonia in patients with autoimmune and inflammatory diseases[J]. Chest, 2020, 158 (6): 2323- 2332.

doi: 10.1016/j.chest.2020.05.558
25
Ishikawa Y , Nakano K , Tokutsu K , et al. Estimation of treatment and prognostic factors of Pneumocystis pneumonia in patients with connective tissue diseases[J]. RMD Open, 2021, 7 (1): e001508.

doi: 10.1136/rmdopen-2020-001508
26
Matteson EL , Kelly C , Distler JHW , et al. Nintedanib in patients with autoimmune disease-related progressive fibrosing interstitial lung diseases: Subgroup analysis of the INBUILD trial[J]. Arthritis Rheumatol, 2022, 74 (6): 1039- 1047.

doi: 10.1002/art.42075
[1] Yuanmei LIU, Yicheng FU, Jingxin HAO, Fuchun ZHANG, Huilin LIU. Construction and validation of a nomogram for predicting in-hospital postoperative heart failure in elderly patients with hip fracture [J]. Journal of Peking University (Health Sciences), 2024, 56(5): 874-883.
[2] LIU Jie,GUO Chao. A prospective cohort study of the influence of positive/negative effectivity on the mortality risk of the Chinese elderly [J]. Journal of Peking University (Health Sciences), 2022, 54(2): 255-260.
[3] Ming-xin AO,Xue-min LI,Yuan-yuan YU,Hui-juan SHI,Hong-shi HUANG,Ying-fang AO,Wei WANG. Effects of visual restoration on dynamic plantar pressure features in elder individuals [J]. Journal of Peking University (Health Sciences), 2021, 53(5): 907-914.
[4] Jian CHEN,Cai-hong ZUO,Cai-yi ZHANG,Ming YANG,Pei-xun ZHANG. Comparison of the effects of two cephalomedullary nails (zimmer natural nail and proximal femoral nail antirotation) in treatment of elderly intertrochan teric fractures [J]. Journal of Peking University(Health Sciences), 2019, 51(2): 283-287.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!