Introduction
Interstitial lung disease (ILD) is characterized by replacement of
normal pulmonary parenchyma with inflammatory cells and/or fibrotic
tissues which results in progressive loss of functional lung units that
impairs gas exchange. Connective tissue diseases (CTDs) are one of the
main causes of ILD and lung involvement is the leading morbidity and
mortality reason in connective tissue disorders [1, 2]. Although ILD
is most commonly observed in systemic sclerosis [3] and rheumatoid
arthritis (RA) it can be seen in nearly all CTDs[4].Due to high
mortality and morbidity of CTD-ILD, selecting optimal immunosuppressive
regimen considering type and severity of underlying rheumatic disease,
progression of pulmonary impairment and drug tolerance/side effects.
Immunosuppressive drugs remain as the main stay of therapy in CTD-ILD.
Azathioprine (AZA) and cyclophosphamide (CYC) are among the most
commonly employed immunosuppressive drugs. AZA inhibits both T and B
cell proliferation[5],whereas CYC, an alkylating agent, inhibits T
cell proliferation by inducing its apoptosis and decreases both humoral
and cellular immune responses[6, 7]. There are several studies
regarding use of CYC as induction regimen in CTD-ILD, which showed clear
benefit in stabilization and improvement in lung functions [8, 9].
Although CYC is effective in preserving lung function, it loses its
efficacy after discontinuation and necessitates long term treatment,
which is significantly limited by its cumulative toxicity. Therefore,
CYC is mostly used in induction regimens, followed by maintenance
therapy with other drugs, such as AZA or mycophenolate mofetil (MMF).In
a retrospective study, AZA was compared with MMF and found to have
similar safety and efficacy for stabilization of lung functions
[10].
Despite its favorable toxicity profile compared to CYC, studies in which
AZA is used in induction regimens are quite scarce. There were two
studies which compared efficacy of AZA and CYC in induction treatment of
systemic sclerosis [3] related ILD, both reported stabilization of
lung functions with AZA[11, 12]. A case series of 11 patients with
primary Sjögren’s syndrome (pSS) related ILD, authors reported favorable
responses with AZA based induction regimen, but lack of a comparator
drug limited implementation of results [13]. To the best of our
knowledge, AZA based regimens in ILD patients with interstitial
pneumonia with autoimmune features (IPAF) has not been previously
reported.
Therefore, studies on efficacy of AZA in CTD-ILD are still needed,
especially for those with IPAF or RA, and also in other cases in which
CYC is contraindicated or not tolerated. Herein, we retrospectively
investigated efficacy and safety of AZA in the treatment of ILD and
compared it with intravenous ( iv) CYC in a relatively large cohort.