Clinical Study of MMF in Treatment of IIM-ILD and Its Effect on Peripheral Blood Treg Cells

Interstitial lung disease (ILD) is a common pulmonary manifestation of idiopathic inflammatory myopathy (IIM). The overall 5-year mortality is 50%. The prognosis is poor and the treatment is challenging.At present, according to the consensus of IIM-ILD experts, glucocorticoids as first-line treatment are often used in high doses and have a variety of adverse reactions. Previous studies have shown that cyclophosphamide (CYC) is effective for IIM-ILD and tends to be used in rapidly progressive interstitial lung disease（RP-ILD）or refractory ILD. However, CYC is an alkylating agent with many toxic and side effects. It is prone to gonadal inhibition, infection, tumor, hemorrhagic cystitis and other risks. At present, Mycophenolate mofetil (MMF) has been widly used in the treatment of IIM, systemic lupus erythematosus (SLE), ANCA associated vasculitis (AAV). The observational research on MMF in the treatment of IIM-ILD shows that it can delay the progress of pulmonary fibrosis and can be used as the first-line treatment of IIM-ILD. Moreover, immune tolerance caused by defects in the number and/or quality of regulatory T cells (Treg) is considered to be a key source of autoimmune diseases. However, it is unclear whether MMF can improve the immune status of IIM-ILD by increasing Treg cells. The aim of this study was to evaluate the effect of MMF for IIM-ILD and its effcts on Treg through a prospective open single arm study, and provide a theoretical basis for the individualized treatment of IIM-ILD, which has important clinical significance.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Inflammatory Myopathy; Interstitial Lung Disease
• Intervention / Treatment: Drug: Mycophenolate Mofetil

Detailed Description

Interstitial lung disease (ILD) is a common pulmonary manifestation of idiopathic inflammatory myopathy (IIM), with an incidence ranging from 23.1 to 65%. The treatment of IIM patients with ILD is challenging, and the overall 5-year mortality is 50%. The disease process of ILD from stable or slow to rapid. Increased mortality and poor prognosis were observed, which needs active treatment. At present, according to the consensus of IIM-ILD experts, glucocorticoids as first-line treatment are often used in high doses, but have a variety of adverse reactions. Previous studies have shown that cyclophosphamide (CYC) is effective for IIM-ILD and tends to be used in rapidly progressive interstitial lung disease（RP-ILD）or refractory ILD. However, CYC is an alkylating agent with many toxic and side effects. It is prone to gonadal inhibition, infection, tumor, hemorrhagic cystitis and other risks. Mycophenolate mofetil (MMF) has been widly used in the treatment of IIM, systemic lupus erythematosus (SLE), ANCA associated vasculitis (AAV). The observational research on MMF in the treatment of IIM-ILD shows that it can delay the progress of pulmonary fibrosis and can be used as the first-line treatment of IIM-ILD. Moreover, immune tolerance caused by defects in the number and / or quality of regulatory T cells (Treg) is considered to be a key source of autoimmune diseases. In transplant patients, studies have found that the combination of MMF and tacrolimus can increase the number of Treg cells in peripheral blood, suggesting that MMF has a certain regulatory effect on Treg cells. Therefore, it is unclear whether MMF can improve the immune status of IIM-ILD by increasing Treg cells, so as to improve the prognosis of the disease. However, it is unclear whether MMF can improve the immune status of IIM-ILD by increasing Treg cells. The aim of this study was to evaluate the effect of MMF for IIM-ILD and its effcts on Treg through a prospective open single arm study, and provide a theoretical basis for the individualized treatment of IIM-ILD.This was a single-arm open-label pilot observational study. Patients were received prednisone (0.5mg-1.0mg/kg/d ) combined with MMF(1.5g-2.0g/d) for 12 months, 4 weeks later, reduced 5mg every two weeks to 10mg/d orally for 3 months, gradually reduced to 7.5mg/ day until 12 months.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lan He; Phone Number: 086-13809156236; Email: Xajdhl87@mail.xjtu.edu.cn
• Study Contact Backup: Name: Yanhua Wang; Phone Number: 086-13571490573; Email: 1367677985@qq.com

Study Locations

• China
  • Xi'an, China, 710061
    • Recruiting
    • Department of Rheumatology,the First Affiliated Hospital of Xi'an Jiaotong University
    • Contact: Lan He; Phone Number: 086-13809156236; Email: Xajdhl87@mail.xjtu.edu.cn
    • Contact: Yanhua Wang; Phone Number: 086-13571490573; Email: 1367677985@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• meet the PM/DM diagnostic criteria according to Bohan-Peter
• consistent with ILD diagnosis
• predicted forced vital capacity (FVC) of at least 50%
• patients who did not use immunosuppress agents (including but not limited to cyclophosphamide, cyclosporine, leflunomide, azathioprine, tacrolimus, etc.) at the time of screening, or who had stopped taking drugs for ≥3 months.

Exclusion Criteria:

• Anti MDA5 antibody positive DM and necrotizing myopathy
• patients if they had other connective tissue diseases, an underlying cancer, a concomitant active infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A single-arm open-label pilot observational study; Patients were received prednisone(0.5mg-1mg/kg/day) and a combination with MMF (1.5g-2.0g/d).	Drug: Mycophenolate Mofetil; Prednisone 0.5-1.0 mg/kg/d, the dose was gradually reduced, and after 4 weeks, the dose was reduced by 5mg every two weeks, and then reduced to 10mg/d for 4-6 months after oral administration for 3 months, and then reduced to 7.5mg/d for maintenance therapy until 12 months;; MMF1.5g-2.0g/d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FVC % predicted	Percentage of predicted FVC	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLCO % predicted	Percentage of predicted DLCO	12 months
Lung high resolution CT score	Lung high resolution CT score	12 months
TDI	Transitional dyspnoea index	12 months
TIS	Clinical response	12 months
Overall survival rate	Overall survival rate%	12 months
Infection rate	Infection rate%	12 months

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Investigators: Study Chair: Lan He, First Affiliated Hospital Xi'an Jiaotong University

Publications and helpful links

General Publications

• Long K, Danoff SK. Interstitial Lung Disease in Polymyositis and Dermatomyositis. Clin Chest Med. 2019 Sep;40(3):561-572. doi: 10.1016/j.ccm.2019.05.004.
• Nihtyanova SI, Brough GM, Black CM, Denton CP. Mycophenolate mofetil in diffuse cutaneous systemic sclerosis--a retrospective analysis. Rheumatology (Oxford). 2007 Mar;46(3):442-5. doi: 10.1093/rheumatology/kel244. Epub 2006 Aug 9.
• Edge JC, Outland JD, Dempsey JR, Callen JP. Mycophenolate mofetil as an effective corticosteroid-sparing therapy for recalcitrant dermatomyositis. Arch Dermatol. 2006 Jan;142(1):65-9. doi: 10.1001/archderm.142.1.65.
• Antiga E, Kretz CC, Klembt R, Massi D, Ruland V, Stumpf C, Baroni G, Hartmann M, Hartschuh W, Volpi W, Del Bianco E, Enk A, Fabbri P, Krammer PH, Caproni M, Kuhn A. Characterization of regulatory T cells in patients with dermatomyositis. J Autoimmun. 2010 Dec;35(4):342-50. doi: 10.1016/j.jaut.2010.07.006. Epub 2010 Sep 16.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): November 30, 2023

Study Registration Dates

• First Submitted: November 10, 2021
• First Submitted That Met QC Criteria: November 10, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Actual): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 10, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Mycophenolate Mofetil; interstitial lung disease; Treg; Th17; Idiopathic inflammatory myopathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Lung Diseases; Muscular Diseases; Myositis; Lung Diseases, Interstitial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: XJTU1AF2020LSK-194

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No