MMF en Morphea

Effectiveness and Tolerability of Mycophenolate Mofetil and Mycophenolic Acid for the Treatment of Morphea

JAMA Dermatology

TAKE-HOME MESSAGE

• This multicenter retrospective cohort study included patients from 8 academic centers. Of 77 patients with morphea treated with mycophenolate mofetil (MMF) or mycophenolic acid (MPA), 49 (64%) had severe disease. A total of 65 patients (84%) received mycophenolate after treatment failure with another medication and, of these, most (n = 48, 74%) were treated initially with methotrexate.

• After 3 to 6 months, 66 of 73 patients (90%) had achieved a beneficial response, defined as stable or improved disease, from mycophenolate. Overall, 7 of 54 patients (13%) had progressive disease despite mycophenolate therapy at 9 to 12 months. Of 12 patients who received mycophenolate as initial therapy, either alone or in combination, 8 achieved a beneficial response and 6 achieved disease remission after 9 to 12 months. Overall, 12 patients discontinued mycophenolate due to adverse effects.

– Caitlyn T. Reed, MD

Written by

 

 

Joseph C English III MD

Extrapolating from its effectiveness in systemic sclerosis, a multicenter, retrospective, cohort study investigated mycophenolate treatment in 77 patients with linear scleroderma and generalized and pan-sclerotic morphea. Of these, 70 received mycophenolate mofetil. Patients with concomitant eosinophilic fasciitis and/or lichen sclerosis were excluded. Overall, 12 patients received initial treatment with mycophenolate, while 65 patients received mycophenolate after previous treatment as monotherapy or combination therapy (phototherapy, 22%; hydroxychloroquine, 31%; topical therapy, 65%; systemic corticosteroids, 65%; methotrexate, 74%) were deemed ineffective. A beneficial response was considered as stable or improved disease. Overall, a beneficial response was seen in 90% (66 of 73) at 3 to 6 months and in 87% (47/54) at 9 to 12 months with initiation/addition of mycophenolate. After 9 to 12 months, 6 of 12 initial therapy patients achieved disease remission, of which 5 of 6 responders were concurrently on methotrexate or systemic steroids. Adverse effects with concurrent systemic therapies were higher than in previous studies in systemic sclerosis, but not severe (cytopenia, 4%).

Although being a retrospective study and not being able to control variables, it does appear that mycophenolate is an option to add to concurrent standard therapies for aggressive cases of morphea. Combination therapy of mycophenolate and methotrexate is concerning for increased myelosuppression, but this cohort reported a low incidence. I have usually transitioned these patients off methotrexate and continued mycophenolate by itself. As with most rare dermatologic diseases, double-blinded, controlled studies are nearly impossible. Medical dermatologists know that certain cases often do not respond to standard treatment and/or progress more rapidly. Our colleagues rightly reviewed and demonstrated some hope for these patients with mycophenolate.

Abstract

IMPORTANCE

First-line systemic therapy for morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)-referred to herein as mycophenolate-is recommended; however, evidence to support this recommendation remains weak.

OBJECTIVE

To evaluate the effectiveness and tolerability of mycophenolate for the treatment of morphea.

DESIGN, SETTING, AND PARTICIPANTS

A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with morphea from 8 institutions who were treated with mycophenolate.

MAIN OUTCOMES AND MEASURES

The primary outcome was morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of morphea.

RESULTS

There were 61 female patients (79%) and 16 male patients (21%) in the study, with a median age at disease onset of 36 years (interquartile range, 16-53 years) and median diagnostic delay of 8 months (interquartile range, 4-14 months). Generalized morphea (37 [48%]), pansclerotic morphea (12 [16%]), and linear morphea of the trunk and/or extremities (9 [12%]) were the most common subtypes of morphea identified. Forty-one patients (53%) had an associated functional impairment, and 49 patients (64%) had severe disease. Twelve patients received initial treatment with mycophenolate as monotherapy or combination therapy and 65 patients received mycophenolate after prior treatment was ineffective (50 of 65 [77%]) or poorly tolerated (21 of 65 [32%]). Treatments prior to mycophenolate included methotrexate (48 of 65 [74%]), systemic corticosteroids (42 of 65 [65%]), hydroxychloroquine (20 of 65 [31%]), and/or phototherapy (14 of 65 [22%]). After 3 to 6 months of mycophenolate treatment, 66 of 73 patients had stable (n = 22) or improved (n = 44) disease. After 9 to 12 months of treatment, 47 of 54 patients had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently.

CONCLUSIONS AND RELEVANCE

This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe morphea.

JAMA Dermatology

Evaluation of the Effectiveness and Tolerability of Mycophenolate Mofetil and Mycophenolic Acid for the Treatment of Morphea

JAMA Dermatol 2020 Apr 01;[EPub Ahead of Print], M Arthur, NM Fett, E Latour, H Jacobe, E Kunzler, S Florez-Pollack, J Houser, S Sharma, S Prasad, A Femia, MJ Stern, LK Pappas-Taffer, R Gaffney, AP Fernandez, D Knabel, AR Cardones, N Leung, A Laumann, JM Yu, J Zhao, RA Vleugels, E Tkachenko, K Lo 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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