Systemic Lupus Erythematosus
Conditions
Keywords
SLE, non-renal manifestations
Brief summary
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.
Interventions
DRUGAzathioprine
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
Initial dose of 1440 mg/day for 6 months to be tapered progressively if complete remission had been obtained
Sponsors
Hospital Universitari Vall d'Hebron Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Obtention of complete remission | 24 months | Complete remission will be defined by a SLEDAI\<4 and/or absence of any BILAG A or B after 12 weeks of treatment |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the safety, improvement in biological parameters and reduction of number of extra-renal flares. | 24 months |
Countries
Spain
Outcome results
None listed