A Prospective Observational Study of Mycophenolate Mofetil Treatment in Progressive Diffuse Cutaneous Systemic Sclerosis of Recent Onset

Abstract

Objective.A prospective observational study of mycophenolate mofetil (MMF) treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc) of recent onset.Methods.Twenty-five previously untreated consecutive patients with recent-onset (< 24 mo) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected body surface area (BSA) were compared from initiation of MMF to study end. Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients. Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients.Results.At 18.2 ± 8.73 months of MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 (p = 0.0004) and the affected BSA from 36% ± 16% to 14% ± 13.3% (p = 0.00001). Pulmonary function tests remained stable from initiation of MMF to the end of the study. Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue. Real-time PCR of skin biopsies demonstrated a marked decrease in expression of fibrosis-related genes.Conclusion.Patients with diffuse progressive cutaneous SSc of recent onset treated with MMF experienced marked improvement in skin involvement and stabilization of pulmonary function. Skin biopsies from 3 patients demonstrated histopathological improvement and decreased expression of fibrosis-related genes.

Long‐term efficacy and tolerability of mycophenolate mofetil therapy in diffuse scleroderma skin disease

“…17 In this prospective, observational study of 42 patients with diffuse skin disease taking MMF for the primary indication of skin thickening, MMF was associated with modest improvements in skin scores with a fall in mean mRSS of 3.7 at 12 months and 7.6 at 24 months. This concurs with the findings of Mendoza et al, 7 who demonstrated a mean fall in mRSS of 10.9 after 18 months of MMF therapy in 25 patients with early disease (< 2 years), with a reduction in accumulation of fibrotic tissue as well as real-time polymerase chain reaction demonstrating reduced expression of fibrosisrelated genes in skin biopsies. In a larger, retrospective study by Le et al 9 of 98 patients with a median disease duration of 12.5 months and a baseline mRSS of 23 and a smaller prospective study by Derk et al 8 of 15 patients with a mean disease duration of 13.4 months and baseline mRSS of 22, skin score reductions of 7.9 and 14, respectively, were seen at 12 months.…”

“…This is in contrast to other studies of MMF in the treatment of SSc-ILD which showed modest improvements in FVC; 7,8,[23][24][25] however, this can be explained by the high baseline FVC in our cohort and the low rates of concurrent, progressive ILD. Oral aperture also remained unchanged over the period of follow-up.…”

“…Diffuse disease was defined as skin thickening of the proximal limb or trunk and for the purpose of this study, only those patients with a mRSS ≥ 12 were included in line with recent studies. 7 Skin scores were measured and recorded annually and those with a mRSS < 12 at baseline, a primary indication for MMF other than skin, or < 12 months of therapy, were excluded from efficacy analysis. Disease duration was measured from the onset of the first non-Raynaud's symptom.…”

“…5 It has also been demonstrated in vivo to down-regulate production of transforming growth factor beta, which is thought to result in reduced deposition of extracellular matrix and hence is a promising therapy in fibrotic disorders. 6 MMF has been associated with improvement in skin thickening in several observational studies in SSc, [7][8][9] and more recently, in the Scleroderma Lung Study II (SLS II). 10 This randomized controlled study compared the effect of CYC and MMF on forced vital capacity (FVC) in ILD in patients with diffuse or limited SSc.…”

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“…Although the toxicity of MMF appears tolerable, the longterm toxicity of MMF in this setting remains unknown. Whether MMF has additional disease-modifying benefits such as in improving the cutaneous involvement of SSc remains unclear 13,14,15,16 . Finally, as the authors note, it is unclear how long patients should be treated with MMF to avoid progression of lung fibrosis.…”