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 .