Background/Purpose:

Interstitial
lung disease (ILD) secondary to connective tissue disease (CTD) is most
commonly seen in systemic sclerosis followed by polymyositis and dermatomyositis. 
Anti-synthetase syndrome is a myositis associated
with ILD and antibodies directed against tRNA synthetases. To date, there is no
standard of treatment for ILD secondary to CTD, but retrospective data suggest
that tacrolimus may be an effective therapeutic option. We conducted a
retrospective study to assess the effectiveness of tacrolimus in patients with
ILD secondary to CTD.

Methods:

A chart
review was performed of adult patients with ILD secondary to CTD who received
tacrolimus between December 1, 1996 and December 31, 2014 at a single center
academic hospital.  A diagnosis of ILD was made based on pulmonary function
tests, lung biopsy, high-resolution CT of the chest, and chest radiograph.  The
primary endpoint was improvement or stability in pulmonary function at six
months based on FEV1 (forced expiratory volume in 1 second) and diffusing
capacity for carbon monoxide (DLCO).  Secondary endpoints included imaging
results and clinical measurements at six and 12 months.

Results:

Fifteen cases
of ILD secondary to CTD treated with tacrolimus were identified.  All patients had
a diagnosis of polymyositis, of which two also had systemic lupus erythematosus
and Sjogren’s syndrome. The mean age was 53 years, 86% were females, and 46%
were previous smokers.  Clinical characteristics are reported in Table 1. Baseline
and six month mean creatinine kinase levels (IU/L) were 794 and 97 respectively.
 At six months, FEV1 improved in 50% of patients who had available data and in 43%
of those with anti-synthetase antibodies (Table 2). Two anti-synthetase
positive patients who had DLCO measured at six months showed improvement.  FK506
levels were not significantly different between responders and non-responders.

Conclusion:

Tacrolimus
appears to be a well-tolerated and effective therapy for stabilizing ILD in patients
with CTD, particularly anti-synthetase syndrome.  Our small sample size limits the
ability to determine whether these findings are statistically significant.  Additionally,
several patients were on concomitant mycophenolate mofetil.  To date, no
controlled studies have been conducted to evaluate the effectiveness of
tacrolimus in the treatment of ILD secondary to CTD.  Our findings warrant larger
prospective randomized controlled trials to evaluate and compare the outcomes
of tacrolimus therapy as adjunctive or monotherapy for ILD secondary to CTD.

Disclosures:  H. Chaudhry, None; R.
Tehrani, None; R. Ostrowski, None.