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Rituximab in connective tissue disease–associated interstitial lung disease

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Abstract

Introduction/objectives

To evaluate rituximab (RTX) effectiveness and safety in patients with interstitial lung disease (ILD) related to connective tissue diseases (CTD).

Methods

Retrospective multicenter cohort study, including patients with CTD-ILD, followed in six Portuguese rheumatology departments until November 2018. ILD diagnosis was based on high-resolution CT (HRCT) and/or lung biopsy. Results of HRCT, pulmonary function tests, and 6-min walking test before and after RTX were compared using the Wilcoxon matched pair test. Safety, including adverse events during treatment and reasons for RTX discontinuation, was also analyzed.

Results

A total of 49 patients were included, with rheumatoid arthritis being the commonest CTD (61.2%). The median interval between CTD onset and ILD diagnosis was 4 years (IQR 1–9.5) and median ILD duration at first RTX administration was 1 year (IQR 0–4). The median RTX treatment duration until the last follow-up was 3 years (IQR 1–6). Usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) were the commonest patterns, occurring in 20 and 18 patients, respectively. One year after RTX first administration, there was a stabilization in carbon monoxide diffusing capacity (DLCO; mean + 5.4%, p = 0.12) and improvement in forced vital capacity (FVC; mean + 4.3%, p = 0.03), particularly in patients with NSIP. Patients with UIP had less promising results, but at 1 year, pulmonary function tests remained stable (DLCO + 2.5%, p = 0.77; FVC + 4.2%, p = 0.16). Infection was the main reason for RTX discontinuation and led to two deaths.

Conclusions

RTX seems to be a promising treatment for CTD-ILD patients, particularly when NSIP pattern is present.

Key points

• The use of rituximab in patients with interstitial lung disease related to connective tissue disease is associated with long-standing disease stability in a wide range of systemic rheumatic diseases.

• Efficacy results were particularly impressive in patients with non-specific interstitial pneumonia pattern, although in a subgroup of patients with usual interstitial pneumonia pattern, disease progression was also hold with this treatment.

• In a large number of patients, rituximab was used in monotherapy and as first-line treatment.

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Acknowledgments

The authors would like to thank all the pulmonologists that collaborate with them in the diagnosis and follow-up of these patients.

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Authors and Affiliations

  1. Rheumatology Department, Hospital Garcia de Orta EPE, Avenida Torrado da Silva, 2805-267, Almada, Portugal

    Ana Catarina Duarte, Ana Cordeiro & Maria José Santos

  2. Rheumatology Department, Centro Hospitalar Universitário de São João EPE, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal

    Bruno Miguel Fernandes & Miguel Bernardes

  3. Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte EPE, Avenida Professor Egas Moniz, 1649-035, Lisbon, Portugal

    Patrícia Martins & Inês Cordeiro

  4. Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-035, Lisbon, Portugal

    Patrícia Martins, Inês Cordeiro & Maria José Santos

  5. Rheumatology Department, Centro Hospitalar e Universitário de Coimbra EPE, Quinta dos Vales, São Martinho do Bispo 108, 3041-801, Coimbra, Portugal

    Tânia Santiago

  6. Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal

    Tânia Santiago

  7. Rheumatology Unit, Centro Hospitalar Tondela-Viseu EPE, Avenida Rei Dom Duarte, 3500, Viseu, Portugal

    Maria Inês Seixas

  8. Rheumatology Unit, Hospital de Braga, Sete Fontes - São Victor, 4710-243, Braga, Portugal

    Ana Roxo Ribeiro

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  1. Ana Catarina Duarte
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  2. Ana Cordeiro
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  10. Maria José Santos
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Correspondence to Ana Catarina Duarte.

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This study was conducted according to the principles of the Declaration of Helsinki (revised in Fortaleza – 2013) and after approval from the Ethics Committee of Hospital Garcia de Orta.

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Duarte, A.C., Cordeiro, A., Fernandes, B.M. et al. Rituximab in connective tissue disease–associated interstitial lung disease. Clin Rheumatol 38, 2001–2009 (2019). https://doi.org/10.1007/s10067-019-04557-7

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