Benefit of adjunctive tacrolimus in connective tissue disease-interstitial lung disease

Abstract

We evaluated the safety and effectiveness of adjunctive tacrolimus therapy with conventional immunosuppression in patients with severe connective tissue disease-related interstitial lung disease (CTD-ILD). We included patients from our interstitial lung disease (ILD) registry with CTD-ILD, in whom tacrolimus was added to corticosteroids and an additional immunosuppressive agent. Demographic data, clinical features, lung function, radiographic images, and pathologic findings were reviewed. Effectiveness was assessed by comparing pulmonary function tests (PFTs) closest to tacrolimus initiation to PFTs approximately 6-12 months later. Corticosteroid dose at these time points was also evaluated. We report adverse events attributed to tacrolimus. Seventeen patients with CTD-ILD were included in adverse event analysis; twelve were included in efficacy analysis. Length of tacrolimus therapy ranged from 6 to 110 months (mean 38.8 months ± 31.4). The mean improvement in percent predicted total lung capacity was 7.5% ± 11.7 (p = 0.02). Forced vital capacity mean improvement was 7.4% ± 12.5 (p = 0.06). The average decrease in corticosteroid dose at follow-up was 20.3 mg ± 25.2 (p = 0.02) with complete discontinuation in six patients. No patients experienced a life-threatening adverse event attributed to tacrolimus. Tacrolimus can be effective and is well tolerated as an adjunctive therapy and allows tapering of corticosteroids.

Keywords: Autoimmune disease; Idiopathic inflammatory myopathies; Immunosuppression; Interstitial lung disease.

Figure 1

Enrollment DM: dermatomyositis; PM: polymyositis; IIM: idiopathic inflammatory myopathy; UCTD: undifferentiated connective tissue disease; ILD: interstitial lung disease Five of seventeen patients (one with dermatomyositis, one with anti-synthetase syndrome, three with UCTD) were excluded from efficacy analysis due to incomplete data. These patients were included in adverse event analysis.

Figure 2

Figure 2a. Change in FVC with tacrolimus Change in forced vital capacity (FVC) from baseline PFTs to those at follow-up 4–13 months after tacrolimus start. Mean baseline FVC was 59.4% ± 17.4 with a mean improvement of 7.4% ± 12.5 (p = 0.06). Figure 2b. Change in DLCO with tacrolimus Change in diffusion capacity of the lung for carbon monoxide (DLCO) percent predicted from baseline PFTs to those at follow-up 4–13 months after tacrolimus start. Mean baseline DLCO was 47.4% ± 13.6 with a mean improvement of 10.0% ± 17.0 (p = 0.02). Figure 2c. Change in prednisone dose with tacrolimus Change in prednisone dose (mg) from the clinic visit nearest the baseline PFTs to the visit nearest follow-up PFTs 4–13 months after tacrolimus start. Mean average decrease in prednisone dose at follow-up was 20.3 ± 25.2 (p=0.02). Of note, patient 4’s increase in prednisone dose is a result of comparing dosages from the clinic visit nearest baseline and follow-up PFTs. His baseline PFT was performed two months before tacrolimus initiation, and his clinical course necessitated an increase in prednisone to 40 mg by the time of tacrolimus initiation.

Figure 2

Figure 2a. Change in FVC with tacrolimus Change in forced vital capacity (FVC) from baseline PFTs to those at follow-up 4–13 months after tacrolimus start. Mean baseline FVC was 59.4% ± 17.4 with a mean improvement of 7.4% ± 12.5 (p = 0.06). Figure 2b. Change in DLCO with tacrolimus Change in diffusion capacity of the lung for carbon monoxide (DLCO) percent predicted from baseline PFTs to those at follow-up 4–13 months after tacrolimus start. Mean baseline DLCO was 47.4% ± 13.6 with a mean improvement of 10.0% ± 17.0 (p = 0.02). Figure 2c. Change in prednisone dose with tacrolimus Change in prednisone dose (mg) from the clinic visit nearest the baseline PFTs to the visit nearest follow-up PFTs 4–13 months after tacrolimus start. Mean average decrease in prednisone dose at follow-up was 20.3 ± 25.2 (p=0.02). Of note, patient 4’s increase in prednisone dose is a result of comparing dosages from the clinic visit nearest baseline and follow-up PFTs. His baseline PFT was performed two months before tacrolimus initiation, and his clinical course necessitated an increase in prednisone to 40 mg by the time of tacrolimus initiation.

Figure 2

Figure 2a. Change in FVC with tacrolimus Change in forced vital capacity (FVC) from baseline PFTs to those at follow-up 4–13 months after tacrolimus start. Mean baseline FVC was 59.4% ± 17.4 with a mean improvement of 7.4% ± 12.5 (p = 0.06). Figure 2b. Change in DLCO with tacrolimus Change in diffusion capacity of the lung for carbon monoxide (DLCO) percent predicted from baseline PFTs to those at follow-up 4–13 months after tacrolimus start. Mean baseline DLCO was 47.4% ± 13.6 with a mean improvement of 10.0% ± 17.0 (p = 0.02). Figure 2c. Change in prednisone dose with tacrolimus Change in prednisone dose (mg) from the clinic visit nearest the baseline PFTs to the visit nearest follow-up PFTs 4–13 months after tacrolimus start. Mean average decrease in prednisone dose at follow-up was 20.3 ± 25.2 (p=0.02). Of note, patient 4’s increase in prednisone dose is a result of comparing dosages from the clinic visit nearest baseline and follow-up PFTs. His baseline PFT was performed two months before tacrolimus initiation, and his clinical course necessitated an increase in prednisone to 40 mg by the time of tacrolimus initiation.

Figure 3

Figure 3a. Patient 1 HRCT Before Tacrolimus Treatment 12/2008: HRCT during patient 1’s initial hospitalization demonstrates reticulonodular interstitial abnormalities and patchy ground-glass opacities bilaterally. Figure 3b. Patient 1 HRCT After Tacrolimus Treatment 10/2009: HRCT 6 months post-tacrolimus initiation reveals that the reticular interstitial opacities are less coarse and ground-glass opacities are decreased.

Figure 3

Figure 3a. Patient 1 HRCT Before Tacrolimus Treatment 12/2008: HRCT during patient 1’s initial hospitalization demonstrates reticulonodular interstitial abnormalities and patchy ground-glass opacities bilaterally. Figure 3b. Patient 1 HRCT After Tacrolimus Treatment 10/2009: HRCT 6 months post-tacrolimus initiation reveals that the reticular interstitial opacities are less coarse and ground-glass opacities are decreased.