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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Azathioprine
* Drug: Enteric-Coated Mycophenolate Sodium


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: azathioprine<br> | Drug: Azathioprine<br>* 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<br>|
| Active Comparator: Enteric-coated Mycophenolate Sodium<br> | Drug: Enteric-Coated Mycophenolate Sodium<br>* Initial dose of 1440 mg/day for 6 months to be tapered progressively if complete remission had been obtained<br>|

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety, improvement in biological parameters and reduction of number of extra-renal flares. |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, non-renal manifestations