Treatment Outcome in Early Diffuse Cutaneous Systemic Sclerosis (ESOS)

The aim of the study is to compare the effectiveness of commonly used immunosuppressant treatments for early diffuse cutaneous systemic sclerosis (SSc).

Study Overview

• Status: Completed
• Conditions: Early Diffuse Cutaneous Systemic Sclerosis
• Intervention / Treatment: Drug: Methotrexate; Drug: Mycophenolate mofetil; Drug: Cyclophosphamide

Detailed Description

Diffuse cutaneous systemic sclerosis (SSc) is a rare autoimmune disease characterised by excessive connective tissue in the skin (causing skin thickening called 'scleroderma'), muscle, joints and internal organs. A number of different drugs with effects on the immune system (known as 'immunosuppressants') are currently being used by clinicians in the treatment of early diffuse cutaneous SSc, but all can have significant side effects. We want to know whether any one is definitely effective and, if so, which is the most effective.

• Study Type: Observational
• Enrollment (Actual): 320

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Eligibility:

Age > 18 Skin thickening < 3 years Immunosuppressant use < 4 months Proximal skin involvement to face/neck, elbow or knee

Description

Inclusion Criteria:

Age > 18 Skin thickening < 3 years Immunosuppressant use < 4 months Proximal skin involvement to face/neck, elbow or knee

Exclusion Criteria:

Previous use of more than 4 months of methotrexate, mycophenolate mofetil, cyclophosphamide or other immunosuppressive treatments

Previous use of immunosuppressant therapy other than methotrexate, mycophenolate mofetil or cyclophosphamide within previous months

Previous stem cell transplantation therapy

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Methotrexate; Patients treated with Methotrexate at the entry of the study.	Drug: Methotrexate; Immunosuppressant agent. Patients treated with Methotrexate at the entry of the study, either oral or subcutaneous with a target dose of 20-25mg weekly.
Mycophenolate Mofetil; Patients treated with Mycophenolate Mofetil at the entry of the study.	Drug: Mycophenolate mofetil; Immunosuppressant agent. Patients treated with Methotrexate at the entry of the study,recommended dose 500 mg twice daily for 2 weeks increasing to 1gm twice daily.
Cyclophosphamide; Patients treated with Cyclophosphamide at the entry of the study	Drug: Cyclophosphamide; Immunosuppressant agent. Patients treated with Methotrexate at the entry of the study, recommend use (i) IV. Minimum monthly dose 500mg/m2 with a recommended duration of 6-12 months. (ii) Oral. 1-2mg/day with a recommended duration of 12 months.
No Immunosuppressant; Patients without immunosuppressant treatment at the entry of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Skin score as measured by modified rodnan skin score	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Pulmonary function as measured by right ventricular systolic pressure (RVSP) or pulmonary artery pressure (PAP)	24 months
Echocardiographic findings	24 months
Cochin hand function	24 months
Fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT) scale	24 months
Short form 36 questionnaire (SF-36)	24 months
Scleroderma Health Assessment Questionnaire	24 months
Haemoglobin	24 months
Erythrocyte sedimentation rate	24 months
Estimated glomerular filtration rate (eGFR)	24 months

Collaborators and Investigators

• Sponsor: University of Manchester
• Investigators: Principal Investigator: Ariane Herrick, MD, phD, University of Manchester

Publications and helpful links

General Publications

• Herrick AL, Peytrignet S, Lunt M, Pan X, Hesselstrand R, Mouthon L, Silman AJ, Dinsdale G, Brown E, Czirjak L, Distler JHW, Distler O, Fligelstone K, Gregory WJ, Ochiel R, Vonk MC, Ancuta C, Ong VH, Farge D, Hudson M, Matucci-Cerinic M, Balbir-Gurman A, Midtvedt O, Jobanputra P, Jordan AC, Stevens W, Moinzadeh P, Hall FC, Agard C, Anderson ME, Diot E, Madhok R, Akil M, Buch MH, Chung L, Damjanov NS, Gunawardena H, Lanyon P, Ahmad Y, Chakravarty K, Jacobsen S, MacGregor AJ, McHugh N, Muller-Ladner U, Riemekasten G, Becker M, Roddy J, Carreira PE, Fauchais AL, Hachulla E, Hamilton J, Inanc M, McLaren JS, van Laar JM, Pathare S, Proudman SM, Rudin A, Sahhar J, Coppere B, Serratrice C, Sheeran T, Veale DJ, Grange C, Trad GS, Denton CP. Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study. Ann Rheum Dis. 2018 Apr;77(4):563-570. doi: 10.1136/annrheumdis-2017-211912. Epub 2018 Jan 6.
• Herrick AL, Pan X, Peytrignet S, Lunt M, Hesselstrand R, Mouthon L, Silman A, Brown E, Czirjak L, Distler JHW, Distler O, Fligelstone K, Gregory WJ, Ochiel R, Vonk M, Ancuta C, Ong VH, Farge D, Hudson M, Matucci-Cerinic M, Balbir-Gurman A, Midtvedt O, Jordan AC, Jobanputra P, Stevens W, Moinzadeh P, Hall FC, Agard C, Anderson ME, Diot E, Madhok R, Akil M, Buch MH, Chung L, Damjanov N, Gunawardena H, Lanyon P, Ahmad Y, Chakravarty K, Jacobsen S, MacGregor AJ, McHugh N, Muller-Ladner U, Riemekasten G, Becker M, Roddy J, Carreira PE, Fauchais AL, Hachulla E, Hamilton J, Inanc M, McLaren JS, van Laar JM, Pathare S, Proudman S, Rudin A, Sahhar J, Coppere B, Serratrice C, Sheeran T, Veale DJ, Grange C, Trad GS, Denton CP. Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS). Ann Rheum Dis. 2017 Jul;76(7):1207-1218. doi: 10.1136/annrheumdis-2016-210503. Epub 2017 Feb 10.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: January 12, 2015
• First Posted (ESTIMATE): January 15, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): May 13, 2016
• Last Update Submitted That Met QC Criteria: May 12, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Systemic sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Antitubercular Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Antibiotics, Antitubercular; Cyclophosphamide; Methotrexate; Mycophenolic Acid
• Other Study ID Numbers: 10H101429