Mycophenolate Mofetil for Eosinophilic Fasciitis: A Retrospective Analysis From 3 Tertiary Care Centers | Dermatology | JAMA Dermatology | JAMA Network
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Table.  Characteristics and Disease Response to Mycophenolate Mofetil (MMF) in 14 Patients With Eosinophilic Fasciitis
Characteristics and Disease Response to Mycophenolate Mofetil (MMF) in 14 Patients With Eosinophilic Fasciitis
1.
Mazori  DR, Femia  AN, Vleugels  RA.  Eosinophilic fasciitis: an updated review on diagnosis and treatment.   Curr Rheumatol Rep. 2017;19(12):74. doi:10.1007/s11926-017-0700-6PubMedGoogle ScholarCrossref
2.
Wright  NA, Mazori  DR, Patel  M, Merola  JF, Femia  AN, Vleugels  RA.  Epidemiology and treatment of eosinophilic fasciitis: an analysis of 63 patients from 3 tertiary care centers.   JAMA Dermatol. 2016;152(1):97-99. doi:10.1001/jamadermatol.2015.3648PubMedGoogle ScholarCrossref
3.
Tull  R, Hoover  WD  III, De Luca  JF, Huang  WW, Jorizzo  JL.  Eosinophilic fasciitis: a case series with an emphasis on therapy and induction of remission.   Drugs Context. 2018;7:212529. doi:10.7573/dic.212529PubMedGoogle Scholar
4.
Loupasakis  K, Derk  CT.  Eosinophilic fasciitis in a pediatric patient.   J Clin Rheumatol. 2010;16(3):129-131. doi:10.1097/RHU.0b013e3181d56f73PubMedGoogle ScholarCrossref
5.
Tashkin  DP, Roth  MD, Clements  PJ,  et al; Sclerodema Lung Study II Investigators.  Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial.   Lancet Respir Med. 2016;4(9):708-719. doi:10.1016/S2213-2600(16)30152-7PubMedGoogle ScholarCrossref
6.
Petrova  DT, Brandhorst  G, Koch  C,  et al.  Mycophenolic acid reverses TGF beta-induced cell motility, collagen matrix contraction and cell morphology in vitro.   Cell Biochem Funct. 2015;33(7):503-508. doi:10.1002/cbf.3149PubMedGoogle ScholarCrossref
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    Research Letter
    April 1, 2020

    Mycophenolate Mofetil for Eosinophilic Fasciitis: A Retrospective Analysis From 3 Tertiary Care Centers

    Author Affiliations
    • 1University of Massachusetts Medical School, Worcester, Massachusetts
    • 2Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts
    • 3The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York
    JAMA Dermatol. 2020;156(5):595-597. doi:10.1001/jamadermatol.2020.0120

    Eosinophilic fasciitis (EF) is a fibrosing disorder characterized by edema, erythema, and induration of the extremities. Eosinophilic fasciitis can cause substantial morbidity from joint contractures, and permanent fibrosis may ensue without timely treatment.1 Corticosteroids are considered first-line therapy; however, long-term treatment with corticosteroid-sparing agents is required to avoid sequelae of chronic steroid use and achieve a durable clinical response.2 Although methotrexate is often considered the first-line corticosteroid-sparing agent for EF, there is no standardized treatment ladder.1,3 To our knowledge, 3 cases of EF have reported favorable outcomes with mycophenolate mofetil (MMF) to date.3,4 Given the paucity of data, we investigated the clinical response of EF to MMF in 3 tertiary care centers.

    Methods

    After approval by the Partners Healthcare and New York University Grossman School of Medicine institutional review boards, including waiver for informed consent given retrospective deidentified data, we performed a search of the Partners Research Patient Data Registry (January 1979-January 2019; Brigham and Women’s and Massachusetts General Hospitals) and 2 medical record databases at New York University Langone Medical Center (January 2005-January 2019) using the terms “eosinophilic fasciitis” and related International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, “mycophenolate mofetil,” “mycophenolic acid,” “myfortic,” “cellcept,”and “MMF.” Extracted data included demographics, disease presentation, treatments, and clinical response. The 2 senior authors (A.N.F. and R.A.V.) confirmed the diagnosis of EF and assessed clinical response (CR), defined as complete (halted disease progression, resolution of erythema and edema, and improvement of induration), partial (halted disease progression with incomplete improvement of erythema and edema), or no response (continued disease progression). Halting disease progression is the primary goal in treating EF. Although softening of recently involved areas is possible with appropriate treatment, full resolution of induration, particularly in long-standing disease, is rare and not routinely expected. Thus, complete CR was considered halting of disease progression with some improvement of induration, whereas partial CR was defined as improvement in all parameters other than induration. Functional impairment was defined as joint contractures or restricted mobility secondary to EF.

    Results

    Of 14 patients (8 men and 6 women) with EF treated with MMF, 8 (57%) were treated with MMF given failure or poor tolerance of prior treatment (Table). In all but 1 patient (patient 9), MMF served as a steroid-sparing agent and overlapped with systemic corticosteroids, which were subsequently tapered or discontinued. Mean (range) disease duration at treatment initiation was 16.7 (2-60) months. Average daily dose was 2429 mg. Treatment duration ranged from 6 months to 6 years.

    By 6 months, 10 patients (71%) had partial and 3 (21%) had complete CR; after 1 year of treatment, 7 (50%) achieved complete CR. Of 12 patients with baseline functional impairment, all experienced improvement after 1 year of treatment with MMF. At the time of most recent follow-up, 5 patients (36%) had partial and 8 patients (57%) had complete CR.

    In the 13 patients treated concomitantly with systemic corticosteroids, MMF allowed for corticosteroid discontinuation in 9 (69%) after a median of 13 months of treatment with MMF, with tapering to 10 mg or less of daily prednisone after a median of 3 months. Daily prednisone or equivalent was tapered from a mean of 48 mg to 11.25 mg at most recent follow-up in the remaining 4 patients. In addition, 6 of 9 patients (67%) previously or concurrently receiving other immunomodulators, most commonly methotrexate, were able to discontinue these agents.

    Adverse events included gastrointestinal distress in 7 patients, 3 of whom were transitioned to mycophenolic acid with resolution, 3 of whom had mild symptoms that resolved as they continued therapy, and 1 of whom discontinued MMF without trialing mycophenolic acid given a lack of insurance approval. No other adverse events, including infection, were noted.

    Discussion

    Although often initially responsive to systemic corticosteroids, EF warrants long-term treatment with corticosteroid-sparing agents.2 In this cohort, all but 1 patient responded favorably to MMF, 5 (36%) achieving partial and 8 (57%) achieving complete CR. The 1 nonresponder was lost to follow-up before receiving 12 months of therapy but was able to lower concomitant systemic corticosteroid and methotrexate doses by 6 months. Importantly, most patients (69%) were able to discontinue concurrent systemic corticosteroids, whereas the remainder were able to taper their doses substantially at the time of most recent follow-up. In addition, MMF was efficacious for both recently diagnosed and long-standing, recalcitrant disease where past therapies failed.

    Use of MMF was associated with an immunomodulatory and antifibrotic effect for cutaneous sclerosis in patients with systemic sclerosis in a recent randomized clinical trial, improving modified Rodnan skin index scores.5 Mycophenolate mofetil is thought to decrease fibroblast activity and collagen synthesis through inhibition of the TGF-β pathway, which plays a prominent role in fibrosis-related diseases.6 Such evidence supports the use of MMF in other sclerosing skin conditions, including EF. Given increasing data on the efficacy of MMF for cutaneous sclerosis, the authors use MMF not only for patients who fail or have a contraindication to methotrexate, but also as first-line corticosteroid-sparing therapy in some patients with moderate-to-severe EF. Although there is no comparative data on the efficacy of methotrexate vs MMF in sclerosing disorders, there is increasing evidence to support the use of MMF given its potential antifibrotic effects in addition to its immunomodulatory properties.5 Therefore, the authors’ standard of care has shifted to using either methotrexate or MMF as first-line corticosteroid-sparing therapy for patients with EF.

    Limitations of this study include its retrospective nature, small sample size, and lack of existing outcome measures to assess disease activity in patients with EF. Despite these limitations, this is the largest study of MMF in the treatment of EF, demonstrating the potential efficacy of MMF in this refractory and debilitating orphan disease.

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    Article Information

    Corresponding Author: Ruth Ann Vleugels, MD, MPH, Autoimmune Skin Disease Program, Department of Dermatology, Brigham & Women’s Hospital, 221 Longwood Ave, Boston, MA 02115 (rvleugels@bwh.harvard.edu).

    Accepted for Publication: January 3, 2020.

    Published Online: April 1, 2020. doi:10.1001/jamadermatol.2020.0120

    Author Contributions: Drs Femia and Vleugels had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Mss Tkachenko and Steuer (co-first authors). Drs Femia and Vleugels (co–senior authors).

    Study concept and design: Tkachenko, Merola, Femia, Vleugels.

    Acquisition, analysis, or interpretation of data: Tkachenko, Steuer, Lo, LaChance, Femia, Vleugels.

    Drafting of the manuscript: Tkachenko, Steuer, Merola, Vleugels.

    Critical revision of the manuscript for important intellectual content: Tkachenko, Steuer, Lo, LaChance, Femia.

    Statistical analysis: Steuer, Merola.

    Administrative, technical, or material support: Tkachenko, Steuer, Lo, Merola.

    Study supervision: LaChance, Femia, Vleugels.

    Conflict of Interest Disclosures: Dr Merola is a consultant and/or investigator for Merck Research Laboratories, Abbvie, Dermavant, Eli Lilly and Company, Novartis, Janssen, UCB, Celgene, Sanofi Regeneron, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, EMD Serono, and Leo Pharma. He is also a member of the Burrage Capital Management Boston Advisory Board. Dr Vleugels’ career has been supported by a Medical Dermatology Career Development Award from the Dermatology Foundation. No other conflicts are reported.

    References
    1.
    Mazori  DR, Femia  AN, Vleugels  RA.  Eosinophilic fasciitis: an updated review on diagnosis and treatment.   Curr Rheumatol Rep. 2017;19(12):74. doi:10.1007/s11926-017-0700-6PubMedGoogle ScholarCrossref
    2.
    Wright  NA, Mazori  DR, Patel  M, Merola  JF, Femia  AN, Vleugels  RA.  Epidemiology and treatment of eosinophilic fasciitis: an analysis of 63 patients from 3 tertiary care centers.   JAMA Dermatol. 2016;152(1):97-99. doi:10.1001/jamadermatol.2015.3648PubMedGoogle ScholarCrossref
    3.
    Tull  R, Hoover  WD  III, De Luca  JF, Huang  WW, Jorizzo  JL.  Eosinophilic fasciitis: a case series with an emphasis on therapy and induction of remission.   Drugs Context. 2018;7:212529. doi:10.7573/dic.212529PubMedGoogle Scholar
    4.
    Loupasakis  K, Derk  CT.  Eosinophilic fasciitis in a pediatric patient.   J Clin Rheumatol. 2010;16(3):129-131. doi:10.1097/RHU.0b013e3181d56f73PubMedGoogle ScholarCrossref
    5.
    Tashkin  DP, Roth  MD, Clements  PJ,  et al; Sclerodema Lung Study II Investigators.  Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial.   Lancet Respir Med. 2016;4(9):708-719. doi:10.1016/S2213-2600(16)30152-7PubMedGoogle ScholarCrossref
    6.
    Petrova  DT, Brandhorst  G, Koch  C,  et al.  Mycophenolic acid reverses TGF beta-induced cell motility, collagen matrix contraction and cell morphology in vitro.   Cell Biochem Funct. 2015;33(7):503-508. doi:10.1002/cbf.3149PubMedGoogle ScholarCrossref
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