The Efficacy and Safety of JAK Inhibitor in the Treatment of Anti-MDA5 Antibody-positive Dermatomyositis Patients

NCT04966884 | Unknown Phase 4

• 1 other identifier: XJTU1AF2020LSK-193
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Anti-melanoma differentiation-associated gene5 (Anti-MDA5) antibody positive Dermatomyositis (DM) is a subtype of DM that is more frequent in East Asia, which is often exhibit skin lesion, clinically amyopathic and interstitial lung disease. About 42%-100% of patients with Anti-MDA5+ DM develop rapidly progressive interstitial lung disease (RPILD) and result in respiratory failure. The mortality is as high as 40% within 6 months. In addition, not every patient with Anti-MDA5+ DM respond to traditional treatment strategy and most of the patients are resistant to immunosuppressive therapy including a combination of high dose glucocorticoids (GCs) and immunosuppressants such as cyclosporine, tacrolimus, or cyclophosphamide. However, RP-ILD is still the main cause of death due to fatal respiratory failure. Therefore, treatment of Anti-MDA5+ DM patients is challenging.Blocking multiple cytokines may become a new target for the treatment of this disease.Jakinibs is a Janus kinase (JAK) inhibitor that blocks a variety of cytokines, such as type I and type II interferon. Few studies have reported a positive response to JAK inhibitor for Anti-MDA5+ DM. Kazuhiro et al. reported in 2018 that JAK inhibitor tofacitinib may be an effective treatment option for high risk amyopathic dermatomyositis (ADM) -ILD patients after failure of conventional treatment, but the number of cases is too small. And a recent paper showed that great efficacy of tofacitinib for the improvement of survival of anti-MDA5-positive early-stage ADM-ILD patients.The aim of this study is to evaluate the efficacy and safety of JAK inhibitors in the treatment of anti-MDA5+ DM patients, and to evaluate the effect of JAK inhibitors on B cells of these patients, so as to provide a new target and theoretical basis for the treatment of anti-MDA5+ DM.

Conditions

Dermatomyositis, Adult Type

Keywords

Dermatomyositis,Tofacitinib,anti-MDA5 antibody

Outcome Measures

Primary Outcomes (1)

• TIS

  the number of responders by total improvement score

  12 months

Secondary Outcomes (5)

• FVC % predicted

  12 months

• DLCO % predicted

  12 months

• Lung high resolution CT score

  12 months

• Overall survival rate

  12 months

• Infection rate

  12 months

Study Arms (1)

A single-arm open-label pilot observational study

EXPERIMENTAL

Patients were received a glucocorticoids (0.8mg-1mg/kg/day) and a combination with tofacitinib (at a dose of 5 mg twice daily).

Drug: JAK Inhibitor

Interventions

JAK Inhibitor DRUG

1. Prednisone 0.8-1.0 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; 2. Tofacitinib 5 mg twice daily for 12 months.

A single-arm open-label pilot observational study

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients fulfilled the Bohan and Peter criteria;
• anti-MDA5 antibody positive;
• patients who were not receiving treatment, or previously diagnosed with anti- MDA5-positive DM, who did not use biological agents (including but not limited to rituximab, infliximab, adalimumab, etanercept, tofacitinib, etc.) at the time of screening, or who had stopped taking drugs for ≥3 months;

You may not qualify if:

• patients if they had other connective tissue diseases, an underlying cancer, a concomitant infection, or a liver aminotransferase level greater than 2 times the upper limit of the normal range.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead

Study Sites (1)

Department of Rheumatology, the First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

RECRUITING

Related Publications (4)

• Kurtzman DJB, Vleugels RA. Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis: A concise review with an emphasis on distinctive clinical features. J Am Acad Dermatol. 2018 Apr;78(4):776-785. doi: 10.1016/j.jaad.2017.12.010. Epub 2017 Dec 9.

  PMID: 29229575 RESULT

• Huang K, Vinik O, Shojania K, Yeung J, Shupak R, Nimmo M, Avina-Zubieta JA. Clinical spectrum and therapeutics in Canadian patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis: a case-based review. Rheumatol Int. 2019 Nov;39(11):1971-1981. doi: 10.1007/s00296-019-04398-2. Epub 2019 Aug 2.

  PMID: 31375890 RESULT

• Kurasawa K, Arai S, Namiki Y, Tanaka A, Takamura Y, Owada T, Arima M, Maezawa R. Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology (Oxford). 2018 Dec 1;57(12):2114-2119. doi: 10.1093/rheumatology/key188.

  PMID: 30060040 RESULT

• Chen Z, Wang X, Ye S. Tofacitinib in Amyopathic Dermatomyositis-Associated Interstitial Lung Disease. N Engl J Med. 2019 Jul 18;381(3):291-293. doi: 10.1056/NEJMc1900045. No abstract available.

  PMID: 31314977 RESULT

MeSH Terms

Conditions

Dermatomyositis

Interventions

Janus Kinase Inhibitors

Condition Hierarchy (Ancestors)

Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Lan He

  First Affiliated Hospital Xi'an Jiaotong University

  STUDY CHAIR

Central Study Contacts

Lan He

CONTACT

086-13809156236; Xajdhl87@mail.xjtu.edu.cn

Yanhua Wang

CONTACT

086-13571490573; 1367677985@qq.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: July 19, 2021
• Study Start: April 2, 2020
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2021
• Last Updated: July 19, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)