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

Vall d'Hebron University Hospital (HUVH)

Status and phase

Completed

Phase 4

Conditions

Systemic Lupus Erythematosus

Treatments

Drug: Enteric-Coated Mycophenolate Sodium

Drug: Azathioprine

Study type

Interventional

Funder types

Other

Identifiers

NCT01112215

2008-008934-35

Details and patient eligibility

About

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.

Enrollment

240 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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.