Mycophenolate mofetil for methotrexate-resistant juvenile localized scleroderma

Abstract

Objectives To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma. Methods Consecutive juvenile localized scleroderma patients undergoing systemic treatment were included in a retrospective longitudinal study. Patients treated with MMF because they were refractory or intolerant to MTX (MMF-group) were compared with responders to MTX (MTX-group). Disease activity was assessed by Localized Scleroderma Cutaneous Assessment Tool and thermography. Disease course was established on the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan–Meier analysis. Results MMF and MTX groups included 22 and 47 patients, respectively. No significant difference in demographics, follow-up duration and treatment before diagnosis was observed between groups. The most represented clinical subtypes in the MMF-group were pansclerotic morphea and mixed subtype (P = 0.008 and P = 0.029, respectively), and linear scleroderma of the face in the MTX-group (P = 0.048). MMF was started because of MTX resistance (18 patients), relapse during MTX tapering/withdrawal (3 patients) and anaphylaxis to MTX (1 patient). After mean 9.4 years of follow-up, 90.9% of patients on MMF and 100% of those on MTX had inactive disease. No significant difference in relapse-free survival between the groups was found (P = 0.066, log-rank test), although MMF likely induced more persistent remission. MMF was well tolerated and combination of MMF and MTX did not increase its efficacy. Conclusion The present study adds strong evidence on the efficacy and tolerance of MMF in severe and/or MTX-refractory juvenile localized scleroderma. Further controlled studies are needed to prove its efficacy as first line treatment.

Prior elicitation of the efficacy and tolerability of Methotrexate and Mycophenolate Mofetil in Juvenile Localised Scleroderma

“…Since the prior elicitation exercise, two further retrospective studies provide further evidence for the efficacy, safety and tolerability of MMF in LS. A case series of MMF in 22 patients with JLS compared to 47 on MTX showed no significant difference in relapse-free survival between the groups although MMF appeared to induce more persistent remission, and MMF was well tolerated 40 . In a study of 77 participants (all 16 years or older), MMF was well tolerated with 35% achieving disease remission 52 .…”

“…It is an easy to use skin score which can be completed by clinicians in the clinic room without specialist equipment. Reliability has been tested in several cohorts including adults and as an outcome measure in clinical trials 8,[40][41][42][43][44] . The mLoSSI activity component was chosen as the measure of efficacy for the consensus meeting.…”

Treatment of juvenile localized scleroderma: current recommendations, response factors, and potential alternative treatments

“…The majority of patients improved, with 35% of adults and 91% of jLS in remission at last follow-up (13.5 months, 9.4 years, respectively). Although 46% of jLS patients relapsed at a mean time of 31 months, most still achieved disease control, with 50% able to remain in remission off MMF at last follow-up [30 ▪ ]. Studies reported a 10–55% frequency of adverse events but this rarely led to discontinuation of MMF (0–16%).…”

Pediatric morphea state‐of‐the‐art literature review: Reframing morphea as a systemic disease

“…Mycophenolate mofetil (MMF), used either as monotherapy or combination therapy as first‐line treatment or after typical standard of care treatments had failed, led to disease remission in 27 of 77 (35%) of adult and pediatric patients with morphea in a single retrospective cohort study 137 . In another study, 90.9% of children who were refractory or intolerant to MTX achieved sustained remission with MMF at the end of the follow‐up period of 9.4 years 138 . Case reports have described clinical improvement with the use of cyclosporine, 139 tocilizumab, 140 TNF‐α inhibitors, 141,142 tofacitinib, 143,144 and abatacept 145,146 …”

“…137 In another study, 90.9% of children who were refractory or intolerant to MTX achieved sustained remission with MMF at the end of the follow-up period of 9.4 years. 138 Case reports have described clinical improvement with the use of cyclosporine, 139 tocilizumab, 140 TNFα inhibitors, 141,142 tofacitinib, 143,144 and abatacept. 145,146…”