Non-anti-TNF biologic agents are associated with slower worsening of interstitial lung disease secondary to rheumatoid arthritis

Abstract

Objectives

To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD).

Patients and methods

We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was changed in lung function (improvement, stabilization, worsening, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with worsening of ILD.

Results

After 24 months, lung disease was stabilized in 40 patients (57.1%), improved in 8 (11.4%), and worse in 21 (30.0%). One patient (1.4%) died. The factors associated with worsening of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015–0.686]), DAS28 (OR, 1.969 [95%CI, 1.005–3.857]), and smoking (OR, 6.937 [95%CI, 1.378–4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%).

Conclusions

Lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. Non-anti-TNF DMARDs reduce the risk of worsening of lung disease in 90% of patients. The inflammatory activity of RA and smoking, on the other hand, are associated with worsening.

Key Points
• We have performed prospectively evaluated lung and joint function in patients with RA-ILD receiving treatment with various DMARDs.
• In our study, the lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs.
• Neither csDMARDs nor anti-TNF agents were associated with a significant risk of worsening of lung disease, whereas non-anti-TNF bDMARDs could reduce the risk of worsening of lung disease.
• Smoking and poor control of joint involvement were the main factors associated with worsening of lung disease.

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Acknowledgments

Grant for medical researchers of the “Fundación Española de Reumatología”. To the Spanish Rheumatology Society (SER) for the translation of the manuscript.

Funding

Grant for Medical Researchers of the “Fundación Española de Reumatología” 2019.

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Affiliations

Authors

Contributions

NMV participated in the design of the study, carried out patient recruitment and statistical analysis, and drafted the manuscript. FJGN and SMA were a contributor in including patients. They were a major contributor in writing the manuscript and they were a contributor in analyzing and interpreting the patient data. MCAH and MIPM collected radiology data. IUG, MCRB, FGJN, IAO, LPA, and CGC were a major contributor in including patients. AFN: a contributor in writing the manuscript. He was a contributor in analyzing and interpreting the patient data. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Natalia Mena-Vázquez or Sara Manrique-Arija.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Málaga (“Comité de Ética de la Investigación de Málaga”) (Project identification code 4/2015, P15).

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Mena-Vázquez, N., Godoy-Navarrete, F.J., Manrique-Arija, S. et al. Non-anti-TNF biologic agents are associated with slower worsening of interstitial lung disease secondary to rheumatoid arthritis. Clin Rheumatol (2020). https://doi.org/10.1007/s10067-020-05227-9

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Keywords

  • Biologics
  • Interstitial lung disease
  • Non-anti-TNF biologics
  • Rheumatoid arthritis