Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations

Randomized Controlled Trial to Evaluate the Efficacy of Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Induction and Maintenance of Remission of the Extra-renal Lupus Manifestations

Azathioprine is still considered the treatment of choice for the non-renal manifestations of systemic lupus erythematosus (SLE) with an estimated efficacy of 45%.Recently, several studies have demonstrated the efficacy of mycophenolate mofetil/enteric-coated mycophenolate sodium in those cases, but so far, no controlled, randomized comparative study between the two drugs has been conducted. The aim is to perform a randomized, controlled, phase III/IV study comparing enteric-coated mycophenolate (ECMs) with azathioprine for induction and maintenance therapy of the non-renal manifestations of SLE. Methods: Patients with non-renal SLE flares (SLEDAI≥6 and/or BILAG o 2B refractory to full doses of hydroxychloroquine and prednisolone (≥10 mg/d) or with relapsing flares will be included. Patients will be stratified according the flare severity (moderate (SLEDAI<12)-severe (SLEDAI≥12)) and randomized (1:1) into two groups of treatment, EMCs (2gr/d) or AZA (2-2.5mg/kg/d) according to TMPT levels for 6 months. Dose will be progressively tapered based on clinical response up to completing a year of treatment. The main aim is the percentage of complete remission achieved ((SLEDAI <4 and/or absence of any BILAG A o B) at week 12 and 24 for moderate and severe flares, respectively. Secondary objectives include evaluating the reduction in the steroid requirement, number of flares post-treatment, effect on the biological parameters, and impact on quality of life, damage and drug safety. To detect a 20% difference between the two drugs with a 80% statistical power (0.05 alpha error), considering a follow up loss of 20%, a total of 240 patients is required.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Azathioprine; Drug: Enteric-Coated Mycophenolate Sodium

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age>18 years
• Fulfill at least 4 of the 11 criteria for the ACR classification
• Any extra-renal flare with an SLEDAI>6 and/or one BILAG A or 2 B
• Oral corticosteroids>10 mg/day and HCQ > 400 mg/day for at least 30 days prior to inclusion

Exclusion Criteria:

• Presence of active renal disease
• Previous intolerance or hypersensibility to any of the active components
• Active infection
• Unmeasurable levels of TMPT
• Pregnancy
• Presence of a severe flare that requires other immunosuppressive treatment for its control
• Any Psychiatric or social condition that did not ensure the patient´s follow-up and patient´s collaboration
• Previous treatment with EC-MPS or Azathioprine in the last 2 months
• Previous treatment with biological therapy in the last 3 months for anti-TNF therapy or in the last year for anti-CD20 therapy
• ALT or GPT >120 UI/mL non-lupus related in the last 30 days
• Leucopenia <1000x10E6 non-lupus related in the last 30 days
• Symptoms related to other medical conditions non-lupus related such as antiphospholipid syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: azathioprine	Drug: Azathioprine; Initial dose of 2-2.5 mg/kg (according to TMTP levels) for 6 months according the severity of the flare with progressive tapering if complete remission has been obtained
Active Comparator: Enteric-coated Mycophenolate Sodium	Drug: Enteric-Coated Mycophenolate Sodium; Initial dose of 1440 mg/day for 6 months to be tapered progressively if complete remission had been obtained

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Obtention of complete remission	Complete remission will be defined by a SLEDAI<4 and/or absence of any BILAG A or B after 12 weeks of treatment	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety, improvement in biological parameters and reduction of number of extra-renal flares.	24 months

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Investigators: Study Director: JOSEP ORDI-ROS, MD, Vall d'Hebron Hospital; Principal Investigator: JOSEFINA CORTES HERNANDEZ, MD, Vall d'Hebron Hospital

Publications and helpful links

General Publications

• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: April 26, 2010
• First Submitted That Met QC Criteria: April 27, 2010
• First Posted (Estimate): April 28, 2010

Study Record Updates

• Last Update Posted (Estimate): October 4, 2016
• Last Update Submitted That Met QC Criteria: October 3, 2016
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: SLE; non-renal manifestations
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Azathioprine; Mycophenolic Acid
• Other Study ID Numbers: 2008-008934-35