Rheumatology Advance Access originally published online on September 23, 2006
Rheumatology 2006 45(12):1572; doi:10.1093/rheumatology/kel335
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LETTERS TO THE EDITOR |
Mycophenolate mofetil for interstitial lung disease in scleroderma
Department of Pathophysiology, University of Athens School of Medicine and Laiko University hospital, Athens, Greece
Correspondence to: G. E. Tzelepis, MD, University of Athens Medical School, Department of Pathophysiology, 75 M. Asias street, Athens, 11527 Greece. E-mail: gtzelep{at}med.uoa.gr
SIR, In six patients with systemic sclerosis (SSc) and interstitial lung disease (ILD), Liossis et al. [1] reported pulmonary function improvements following first-line treatment with mycophenolate mofetil (MMF) for a period of 4–6 months. The improvements of lung diffusion capacity (DLCO), primarily, and to a lesser extent of forced vital capacity (FVC) along with radiological evidence of infiltrate clearing on chest CT lead the authors to conclude that MMF in conjunction with small doses of steroids may be an effective first-line therapy for these patients.
We would like to report our experience with MMF when used not as a first-line drug but as a long-term immunosuppressive agent following treatment with i.v. cyclophosphamide (CYC). Seven patients (age 58± 11 yrs; 6 women) with SSc and ILD received MMF for a period of 18± 7 months. Initially, patients were treated with MMF 500 mg twice daily for a month. A complete blood count at that point, excluding the development of leucopenia, allowed for escalation of the MMF dosage to 2000 mg/day, which was continued thereafter. All patients had completed therapy with i.v. CYC for a period of 3± 1.4 yrs.
Pulmonary function indices before and after treatment with MMF were measured and compared with those obtained in a case-control group of seven patients (Table 1) who had similarly completed treatment with i.v. CYC but received no long-term immunosuppressive therapy following CYC treatment. As shown in the table, the changes in FVC and DLCO did not differ between the two groups.
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CYC has emerged as the first-line therapy for ILD in SSc. It produces a small but significant effect on FVC (about 2.5% of predicted), when compared with placebo; this modest effect is maintained for about 1 yr following the discontinuation of treatment [2]. Thereafter, the annual loss in the FVC may range from two to eight per cent of the predicted value, being greater for patients with more fibrosis on high-resolution CT [2], as well as during the first 3 yrs from disease onset [3, 4]. In the absence of clinical data, the most appropriate long-term immunosuppressive agent to substitute CYC is unknown. Azathioprine combined with low-dose steroids, a regimen commonly used in idiopathic pulmonary fibrosis despite lack of sufficient evidence of survival improvement, could be an alternative selection [5, 6].
MMF is primarily used in post-transplant patients to suppress acute and chronic allograft rejection [7]. It inhibits purine synthesis through de novo pathways and thus decreases the activity of inflammatory cells including T-, B-lymphocytes and macrophages. Over the last decade, MMF has emerged as a useful therapy not only in solid organ transplantation but also in various autoimmune disorders, largely replacing azathioprine.
Our preliminary data are not in conflict with those reported by Liossis et al. [1] because MMF was used as a maintenance treatment rather than a first-line therapy. In a similar study in which MMF was used as a maintenance therapy following induction with anti-thymocyte globulin, Stratton et al. [8] detected no pulmonary function improvements in 13 patients with SSc. A recent retrospective study [9] on 28 patients who received MMF either as initial immunomodulatory or as maintenance agent for ILD related to various connective tissue diseases reported no significant adverse effects and a trend towards pulmonary function stability after a year (median) of follow up.
These recent reports should encourage the launch of controlled studies that will fully define the role of MMF, used either as initial or as long-term immunosuppressive agent, in treating patients with SSc and ILD.
The authors have declared no conflicts of interest.
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Acknowledgements |
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 Top Acknowledgements References |
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The authors are grateful to Prof. Haralampos M. Moutsopoulos, MD, for his continuous inspiration, guidance and support.
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References |
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TopAcknowledgementsReferences |
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- Liossis SN, Bounas A, Andonopoulos AP. (2006) Mycophenolate mofetil as first-line treatment improves clinically evident early scleroderma lung disease. Rheumatology 45:1005–8.
[Abstract/Free Full Text] - Tashkin DP, Elashoff R, Clements PJ, et al. (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354:2655–6.
[Abstract/Free Full Text] - Steen VD, Conte C, Owens GR, Medsger TA Jr. (1994) Severe restrictive lung disease in systemic sclerosis. Arthritis Rheum 37:1283–9.[ISI][Medline]
- Plastiras SC, Karadimitrakis SP, Ziakas PD, Vlachoyiannopoulos PG, Moutsopoulos HM, Tzelepis GE. (2006) Scleroderma lung: initial forced vital capacity as predictor of pulmonary function decline. Arthritis Rheum 55:598–602.[CrossRef][ISI][Medline]
- Latsi PI and Wells AU. (2003) Evaluation and management of alveolitis and interstitial lung disease in scleroderma. Curr Opin Rheumatol 15:748–55.[CrossRef][ISI][Medline]
- Costabel U and King TE. (2001) International consensus statement on idiopathic pulmonary fibrosis. Eur Respir J 17:163–7.
[Free Full Text] - Jayne D. (1999) Non-transplant uses of mycophenolate mofetil. Curr Opin Nephrol Hypertens 8:563–7.[CrossRef][ISI][Medline]
- Stratton RJ, Wilson H, Black CM. (2001) Pilot study of anti-thymocyte globulin plus mycophenolate mofetil in recent-onset diffuse scleroderma. Rheumatology 40:84–8.
[Abstract/Free Full Text] - Swigris JJ, Olson AL, Fischer A, et al. (2006) Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest 130:30–6.
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