Abstract
The purpose of this study was to assess the impact of enteric-coated mycophenolate sodium (EC-MPS) on skin and pulmonary manifestations of patients with progressive systemic sclerosis (Ssc). A prospective, open-label single-centre trial with EC-MPS 2 × 720mg/day over 12 months and a long-term follow-up of 50 months were conducted. Modified Rodnan skin score (mRSS) was used to assess the skin and pulmonary function tests to assess the pulmonary involvement. In order to quantify the extent of alveolitis/fibrosis via densitometry, the high attenuation value, median lung density and percentiles of lung tissue densities were obtained by high-resolution computed tomography. Eleven patients were included. Three patients had to stop medication before month 6 (2× side effects, 1× progression). For the remaining eight patients, the median mRSS was non-significantly reduced from 13.5 at baseline to 11 at month 12. According to the CT histography, median lung density and high attenuation values remained stable. However, the course of percentiles −200 to −300 and particularly −300 to −400 Hounsfield units slightly increased in seven of eight patients after 12 months, suggesting worsening of pulmonary involvement. Accordingly, median diffusing capacity for carbon monoxide showed a tendency to decline (75.1 % vs. 70.2) while forced vital capacity non-significantly improved (78.0 vs. 85.5 %) during the study. Four patients are still on EC-MPS without clinical signs of progression after 50 months follow-up. EC-MPS showed non-significant improvement of the skin. Pulmonary fibrosis remained stable with only a slight tendency towards progression which might be ascribed to the medication as well as the natural course of the disease. CT histography appears to be a sensitive method for the detection of progression of pulmonary fibrosis and therefore should be considered for further studies in Ssc.
Similar content being viewed by others
References
Tyndall AJ, Bannert B, Vonk M, Airò P, Cozzi F, Carreira PE et al (2010) Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 69(10):1809–15
Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE et al (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354:2655–66
Hoyles RK, Ellis RW, Wellsbury J, Lees B, Newlands P, Goh NS et al (2006) A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum 54:3962–3970
Derk CT, Grace E, Shenin M, Naik M, Schulz S, Xiong W (2009) A prospective open label study of mycophenolate fort he treatment of diffuse systemic sclerosis. Rheumatology 48:1595–99
Stratton RJ, Wilson H, Black CM (2001) Pilot study with antithymocyte globuline plus mycophenolate mofetil in recent-onset diffuse scleroderma. Rheumatology 40:84–88
Vanthuyne M, Blockmans D, Westhovens R, Roufosse F, Cogan E, Coche E et al (2007) A pilot study of mycophenolate mofetil combined to intravenous methylprednisolone pulses and oral low-dose glucocorticoids in severe early systemic sclerosis. Clin Exp Rheumatol 25(2):287–92
Liossis SNC, Bounas A, Andonopoulos AP (2006) Mycophenolate mofetil as first line treatment improves clinically evident early scleroderma lung disease. Rheumatology 45:1005–08
Nihtyanova SI, Brough GM, Black CM, Denton CP (2007) Mycophenolate mofetil in diffuse cutaneous systemic sclerosis—a retrospective analysis. Rheumatology 46:442–445
Le EN, Wigley FM, Shah AA, Boin F, Hummers LK (2011) Long-term experience of mycophenolate mofetil for treatment of diffuse cutaneous systemic sclerosis. Ann Rheum Dis 70(6):1104–7
Mendoza FA, Nagle SJ, Lee JB, Jimenez SA (2012) A prospective observational study of mycophenolate mofetil treatment in progressive diffuse cutaneous systemic sclerosis of recent onset. J Rheumatol 39:1241–7
Simeón-Aznar CP, Fonollosa-Plá V, Tolosa-Vilella C, Selva-O'Callaghan A, Solans-Laqué R, Vilardell-Tarrés M (2011) Effect of mycophenolate sodium in scleroderma-related interstitial lung disease. Clin Rheumatol 30(11):1393–8
Salvadori M, Holzer H, de Mattos A, Sollinger H, Arns W, Oppenheimer F et al (2004) Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant 4(2):231–6
Antoniou KM, Wells AU (2008) Scleroderma lung disease: evolving understanding in light of newer studies. Curr Opin Rheumatol 20(6):686–91
Cavigli E, Camiciottoli G, Diciotti S, Orlandi I, Spinelli C, Meoni E et al (2009) Whole lung densitometry versus visual assessment of emphysema. Eur Radiol 19(7):1686–92
Matsuo S, Yamashiro T, Washko GR, Kurihara Y, Nakajima Y, Hatabu H (2010) Quantitative CT assessment of chronic obstructive pulmonary disease. Radiographics 30:55–66
Camiciottoli G, Orlandi I, Bartolucci M, Meoni E, Nacci F, Diciotti S, Barcaroli C, Conforti ML, Pistolesi M, Matucci-Cerinic M, Mascalchi M (2007) Lung CT densitometry in systemic sclerosis: correlation with lung function, exercise testing, and quality of life. Chest 131(3):672–81
Nannini C, West CP, Erwin PJ, Matteson EL (2008) Effects of cyclophosphamide on pulmonary function in patients with scleroderma and interstitial lung disease: a systematic review and meta-analysis of randomized controlled trials and observational prospective cohort studies. Arthritis Res Ther 10(5):R124
Acknowledgments
This study was supported by an unrestricted grant from Novartis.
Disclosures
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
Joerg C. Henes and Marius Horger contributed equally.
Rights and permissions
About this article
Cite this article
Henes, J.C., Horger, M., Amberger, C. et al. Enteric-coated mycophenolate sodium for progressive systemic sclerosis—a prospective open-label study with CT histography for monitoring of pulmonary fibrosis. Clin Rheumatol 32, 673–678 (2013). https://doi.org/10.1007/s10067-012-2155-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-012-2155-5