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