Background
Interstitial lung disease (ILD) is a relatively common and serious
complication of rheumatoid arthritis (RA)[1]. Its prevalence varies
widely from 3 to 67%, increasing from 2 to 10 fold the risk of death in
RA patients[2]. Moreover, RA-ILD is considered the second most
common cause of death in these patients, just behind cardiovascular
disease[3].
RA-ILD is a heterogeneous disease, involving different ILD subtypes with
different HRCT patterns. Usual interstitial pneumonia (UIP) is the most
frequent imaging pattern, accounting for 40~60% of patients with
RA-ILD, followed by nonspecific interstitial pneumonia for about 40%.
Unclassifiable patterns can be observed in up to 6% of patients[3].
UIP and Idiopathic pulmonary fibrosis (IPF), the most frequent pattern,
have a poor prognosis and low median survival rate[4]. A
meta-analysis of 10 cohort studies, including 1256 patients with RA-ILD,
estimated a 1.6-fold higher risk of death for those with a UIP pattern
than other patterns[5].
RA-UIP shares radiological and histopathological similarities with IPF,
indicating the necessity of saving RA-UIP. However, how to reverse or
stabilize the lesions remains challenging.Therapeutic options in these
patients are complicated by the possible pulmonary toxicity of many
diseases modifying antirheumatic drugs (DMARDs) and by their unclear
efficacy on pulmonary involvement[6].
Tofacitinib is a small-molecule Janus kinase (JAK)1/JAK3, and to a
lesser extent, JAK2/tyrosine kinase(TYK)2 inhibitor approved for the
treatment of RA. JAK/signal transducer and activator of transcription
(STAT) pathway has been implicated in pulmonary fibrosis[7,8]. In
vitro and in vivo studies investigated tofacitinib in ILDs. These
results collectively indicated that tofacitinib is a potential
therapeutic option for RA-UIP[9-12].
Iguratimod (IGU), a small molecule with new anti-inflammatory and
immunomodulatory properties, was developed as a novel anti-rheumatic
drug and is widely used for RA. Researches had also found that IGU could
be an effective therapeutic strategy for pulmonary fibrosis[13-15].
Successful treatment of RA-UIP with tofacitinib combined with IGU has
not been reported yet. Here, we report three cases of RA-UIP, and they
were successfully treated with the combination therapy of tofacitinib
combined with IGU .