Efficacy Of Intermittent Intra-Venous Cyclophosphamide and Cyclosporin A Combination Therapy For Rapidly Progressive Interstitial Lung Disease With Dermatomyositis Associated With Anti-Melanoma Differentiation-Associated Gene 5 Autoantibody Titer

Noriko Sasaki¹, Shinji Sato¹, Shinichi Nogi¹, Naofumi Chinen², Kiri Honda¹, Eiko Saito¹, Chiho Yamada² and Yasuo Suzuki², ¹Rheumatology, Tokai University School of Medicine, Isehara, Japan, ²Division of Rheumatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: antibiotics and dermatomyositis, Lung Disease

Session Information

Title: Muscle Biology, Myositis and Myopathies: Advances in the Epidemiology, Immunology and Therapy of Myositis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Anti-Melanoma Differentiation-Associated Gene 5 (MDA5) autoantibody is present specifically in patients with dermatomyositis (DM), especially those with few or no muscle manifestations (clinically amyopathic dermatomyositis: CADM). It is strongly associated with rapidly progressive interstitial lung disease (RP-ILD). Recently, an association between anti-MDA5 antibody titer measured by enzyme-linked immunosorbent assay (ELISA) and disease activity has been reported in addition to its diagnostic utility for CADM with RP-ILD. However, the relationship between antibody titer and efficacy of intermittent intra-venous cyclophosphamide and cyclosporin A combination therapy had not been reported.

Methods: 7 patients with CADM and RP-ILD positive for anti-MDA5 antibody by RNA and protein immunoprecipitation assay who were seen at our University between 2011 and 2012 were retrospectively evaluated for anti-MDA5 antibody and lung involvement. Anti-MDA5 antibody titers were determined by a previously established ELISA. Patients received combination therapy consisting of intermittent intra-venous cyclophosphamide (0.5 g/m²/month), cyclosporin A (2-4 mg/kg/day) and high dose corticosteroid (1 mg/kg/day orally, then tapering gradually) including pulse therapy (1,000 mg/day for 3 days) over 24-48 weeks. Associations between anti-MDA5 titer and the change in high resolution computed tomography (HRCT) findings after improvement of lung involvement or outcome were analyzed. HRCT findings were evaluated by alveolar and interstitial score proposed by Kazerooni et al.

Results: The combination therapy was effective for all 7 CADM and RP-ILD patients and none of them died during follow-up. There was no correlation between the mean alveolar score and the mean titer of anti-MDA5 antibody before treatment (r=-0.36; P= 0.44). The mean titer of anti-MDA5 antibody significantly decreased after treatment (130.8 units vs. 15.3 units, P= 0.016, cut-off level = ~15 unit). In parallel with the reduced antibody titer, respiratory symptoms improved in all patients and the mean alvelolar score significantly decreased after treatment (10.9 vs. 7.6, P= 0.012), whearas no changes were seen in the mean interstitial score. After improvement of RP-ILD, anti-MDA5 titer remained under the cut-off level over time in 5 of 7 (71%) patients.

Conclusion: These results emphasize the clinical importance of using anti-MDA5 antibodies to monitor disease activity of lung involvement and to evaluate the response to treatment in patients with DM and RP-ILD.

Disclosure:

N. Sasaki,
None;

S. Sato,

Holding a patent on anti-MDA5 antibody-measuring kit,

S. Nogi,
None;

N. Chinen,
None;

K. Honda,
None;

E. Saito,
None;

C. Yamada,
None;

Y. Suzuki,
None.

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