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

Abstract

Objectives: To assess the long-term efficacy and tolerability of mycophenolate mofetil (MMF) in patients with diffuse cutaneous systemic sclerosis (dcSSc).Methods: Patients enrolled in the Australian Scleroderma Cohort study with dcSSc and baseline modified Rodnan skin score (mRSS) ≥ 12 who were treated for a minimum of 12 months with MMF for the primary indication of skin disease were included and their prospectively collected data retrieved. Change in mRSS, the proportion with a clinically significant improvement (reduction in mRSS ≥ 5 from baseline) and adverse effects due to therapy were determined.Results: Seventy-four participants treated with MMF were identified and of these, 42 met inclusion criteria. The mean age was 53 AE 12 years, with mean disease duration at MMF commencement of 4.8 AE 4.3 years. Twentyone participants (50%) commenced MMF within 2 years of disease onset and the mean duration of therapy was 2.7 AE 1.7 years. The mean mRSS at baseline was 25.9 AE 9.2 with a reduction of 3.7 AE 7.1 (P = 0.07) after 1 year of therapy, 7.6 AE 8.3 after 2 years (P = 0.01) and 10.5 AE 10.3 after 5 years (P < 0.01). Response to treatment was not affected by disease duration at MMF commencement or baseline skin score. Eighteen participants (43%) demonstrated clinically significant improvement after 1 year, increasing to 92% after 4 years. Two participants (5%) ceased MMF due to adverse effects.Conclusion: MMF was associated with a modest improvement in mRSS and was well tolerated in the treatment of dcSSc. Given the natural history of dcSSc where skin involvement can spontaneously improve, randomized, placebo-controlled studies are required to confirm whether improvement can be attributed to MMF therapy.

Clinical characteristics, visceral involvement, and mortality in at-risk or early diffuse systemic sclerosis: a longitudinal analysis of an observational prospective multicenter US cohort

“…This difference could be explained by the higher prevalence of RNA polymerase III antibodies in PRESS as these antibodies are associated with a higher peak of mRSS [ 27 ]. Mean mRSS in PRESS is consistent with the results from the Australian or US GENISOS registries [ 9 , 28 ] and with baseline characteristics of patients with early dcSSc in recent RCTs [ 29 – 31 ].…”

Treatment modalities and drug survival in a systemic sclerosis real-life patient cohort

“…It should be noted that in our study a small proportion of patients received per os CYC for 36 or even 48 months, beyond the usual induction drug load, and these patients correspond to a former period when therapeutic choices were limited and prolonged per os CYC treatment was necessary. In the literature, the reported discontinuation rates vary from 30 to 45% for CYC [17,19,30] and from 10 to 40% for MMF after 12 to 24 months of treatment [18,31,32] while another concerning issue is the results from studies reporting recurrence of the disease after CYC or MMF cessation [33,34]. Altogether, the mediocre retention rates of CYC and MMF and the risk of disease relapse after treatment cessation are indicative of the therapeutic predicament that physicians often confront in daily clinical practice and of the need for newer more effective long-term treatments.…”

Successful treatment of children with juvenile systemic sclerosis using mycophenolate mofetil after methylprednisolone pulse therapy: A 3‐year follow‐up

“…However, they are often mild, transient, and tolerable. 1,3,9 In both cases reported here, there were no adverse effects, including renal crisis. Although a comparative study is required, MMF after MPT may be effective in ensuring good control and safety in patients with JSSc skin involvement as well as heart or lung involvement.…”

“…MMF has been reportedly shown to be effective in adult-onset SSc. 1,3,4,6 Mendoza et al reported that MMF was effective in adult-onset SSc skin disease without using other immunosuppressants. 6 MMF can inhibit fibrosis by the direct action on fibroblasts, the inhibition of their proliferation, and the reduction of tissue accumulation of activated myofibroblasts.…”