Clinical trial NCT01112215: Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Systemic Lupus Erythematosus
Keywords: SLE
non-renal manifestations
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
First posted: 2010-04-28
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Obtention of complete remission
timeFrame: 24 months
Secondary outcomes:
measure: To evaluate the safety, improvement in biological parameters and reduction of number of extra-renal flares.
timeFrame: 24 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Vall d'Hebron Hospital
Study officials:
affiliation: VALL D'HEBRON HOSPITAL
name: JOSEP ORDI-ROS, MD
role: STUDY_DIRECTOR
affiliation: VALL D'HEBRON HOSPITAL
name: JOSEFINA CORTES HERNANDEZ, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.