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Original Article
DOI: 10.1016/j.reumae.2020.04.010
Available online 4 December 2020
Systematic review of the impact of drugs on diffuse interstitial lung disease associated with rheumatoid arthritis
Revisión sistemática sobre el impacto de los fármacos en la enfermedad pulmonar intersticial difusa asociada a Artritis Reumatoide
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Carmen Carrasco Cuberoa,
Corresponding author
mcarrascocubero@gmail.com

Corresponding author.
, Eugenio Chamizo Carmonab, Paloma Vela Casasemperec
a Servicio de Reumatología, Hospital Universitario de Badajoz, Badajoz, Spain
b Servicio de Reumatología, Hospital General de Mérida, Mérida, Badajoz, Spain
c Servicio de Reumatología, Hospital General Universitario de Alicante, Alicante, Spain
Received 02 January 2020. Accepted 22 April 2020
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Tables (6)
Table 1. Systematic reviews and meta-analysis.
Table 2. Randomised clinical trials.
Table 3. Studies that evaluate efficacy and survival with csDMARDs.
Table 4. Studies that evaluate efficacy and mortality due to glucocorticoids and immunosuppressants.
Table 5. Cohort and case-control studies of anti-TNF and non-anti-TNF biologics.
Table 6. Table evaluating the quality of results.
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Abstract
Objective

To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD).

Methods

Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed.

Results

1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors.

Conclusions

There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such us TNFi, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.

Keywords:
Rheumatoid arthritis
Diffuse interstitial lung disease
Disease modifying antirheumatic drugs
Systematic review
Abbreviations:
ABA
ACPA
AIP
Anti-TNF
AZA
bDMARD
BSRBR
CPM
csDMARD
CTZ
DLCO
DMARD
ETN
FVC
GC
GOLI
GS
HR
HRCT
IL
ILD
INF
IP
IPF
IR
KL-6
LDH
LE
LEF
MA
MMF
MMP-3
MTX
NS
NSIP
OR
RA
RCTs
RF
RFT
RR
RTX
SAD
SR
SSZ
TCZ
TNF
tsDMARD
UIP
Resumen
Objetivo

Revisar la evidencia disponible sobre la repercusión de los tratamientos de la artritis reumatoide (AR) en la enfermedad pulmonar intersticial difusa (EPID) asociada.

Métodos

Revisión sistemática de estudios que evalúan el impacto del tratamiento farmacológico en pacientes con AR y EPID. Se realizó una búsqueda bibliográfica en MEDLINE, EMBASE y Cochrane, selección de artículos y evaluación de la calidad metodológica (FLC 3.0 OSTEBA) y graduación del nivel de evidencia (SING).

Resultados

Se identificaron 1.720 referencias en búsqueda primaria y 7 en manual o indirecta. Se incluyeron 43 artículos: 7 revisiones sistemáticas, 2 ensayos clínicos aleatorizados, 5 estudios de cohortes, 8 estudios de casos-controles y 21 series de casos. Metotrexato (MTX) y leflunomida (LEF) no aumentan la incidencia, complicaciones ni mortalidad por EPID. Aunque los resultados no son uniformes, los anti-TNF han tenido con frecuencia peores resultados en incidencia, progresión y mortalidad por EPID que MTX, LEF, abatacept (ABA) y rituximab (RTX). La evidencia encontrada es escasa para los inhibidores de JAK quinasas y antifibróticos, y controvertida para los inhibidores de la IL-6.

Conclusiones

No existe evidencia de que MTX o LEF empeoren el pronóstico de los pacientes con AR-EPID. RTX y ABA parecen tener mejores resultados que otros biológicos, como anti-TNF, consiguiendo con frecuencia la estabilización y, en algunos casos, la mejoría de la EPID en pacientes con AR.

Palabras clave:
Artritis reumatoide
Enfermedad pulmonar intersticial difusa
Fármacos antirreumáticos modificadores de enfermedad
Revisión sistemática

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