Enteric-Coated Mycophenolate Sodium Versus Azathioprine for Patients with Moderate/Severe Active Systemic Lupus Erythematosus: Results from a Phase 3, Randomized, Parallel, Multicentre Study

Josefina Cortés-Hernández¹, luis Sáez-Comet², Mercedes Pérez-Conesa², M Rubio Rivas³, Francesca Mitjavila⁴, A. Castro Salomó⁵, Sandra Parra⁶, J. Cuquet Pedragosa⁷, Vera Ortiz-Santamaría⁸, M. Mauri Plana⁹, Segundo Bujan-Rivas¹⁰, P Suñé Martin¹¹, Xavier Vidal¹² and Josep Ordi-Ros¹³, ¹Internal Medicine Department, Vall d´Hebron Hospital, Barcelona, Spain, ²Internal Medicine, Miguel Servet University Hospital, Zaragoza, Spain, ³Internal Medicine, hopital Universitario Bellvitge, Barcelona, Spain, ⁴Internal Medicine, Bellvitge University Hospital, Barcelona, Spain, ⁵Hospital Universitari de Reus, Spain, Reus, Spain, ⁶Internal Medicine, Sant Joan de Reus University Hospital, Reus, Spain, ⁷Internal Medicine, Granollers University Hospital, Granollers, Spain, ⁸Rheumatology, Hospital General. Granollers., Granollers, Spain, ⁹Internal Medicine, Mataró Hospital, Mataró, Spain, ¹⁰Vall d'Hebron Hospital, Barcelona, Barcelona, Spain, ¹¹Pharmacy Department, Vall d'Hebron Hospital, Barcelona, Spain, ¹²Statistical Department, Vall d'Hebron Hospital, Barcelona, Spain, ¹³Internal Medicine, Systemic Autoimmune disease Research Unit. Hospital Vall d'Hebron., Barcelona, Spain

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: SLE and azathioprine

Session Information

Date: Monday, November 14, 2016

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment III: Novel and Current Therapies

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Treatment of non-renal manifestations in systemic lupus erythematosus (SLE) remains challenging. To date, available data on the efficacy, safety and steroid-sparing effects of non-biological therapies is limited and provided mainly by small open-label studies and few randomized controlled trials (RCTs). The aim of the study is to assess the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPs) compared with azathioprine (AZA) for active non-renal SLE.

Methods: This is a 24-month randomized, superiority, open-label, multicenter study (ClinicalTrials.gov: NCT01112215). Adults age ≥18 years with moderate-to-severe active SLE disease were recruited from 13 Hospitals in Spain. Patients were stratified by centre and SLEDAI-2k score (6-9 vs. ≥10) and randomized (1:1) to receive oral EC-MPs (target dose: 1440 mg/day) or azathioprine (target dose: 2 mg/Kg, according to TPMT levels when available), in addition to background therapy with oral prednisone and antimalarial agents. To have a ≥80% statistical power to detect a ~20% difference in clinical response between the 2 study groups, assuming a clinical response in the AZA group at 2 years of 40-50% we calculated we needed 120 patients in each group with a two-sided significance level of 0.05. Statistical analysis was by intention-to-treat. Rates of complete remission (CR) at 3 and 24 months were the primary endpoints. Secondary endpoints included time to CR, rate and time to BILAG A/B or BILAG A flares, reduction of corticosteroids and adverse events.

Results: A total of 240 patients were included. More patients in the EC-MPs group than in the azathioprine group achieved CR at 3 (32.5% vs. 19.2%, p=0.027) and 24 months (71.2% vs. 48.3%, p=0.0005). Time to CR was shorter in the EC-MPs group (hazard ratio, 1.43; 95% CI, 1.07 to 1.91; P=0.017). BILAG A/B flares were observed in 86 (71.7%) AZA-treated and 60 (50%) EC-MPs-treated patients (p=0.001). Time to first flare was longer with EC-MFs (hazard ratio, 1.81; 95% CI, 1.3 to 2.56; p=0.0004). New BILAG A flares occurred in 26 (21.7%) AZA-treated and 10 (8.3%) EC-MPs-treated patients (p=0.004). Time to severe flare was longer in the EC-MPs group (hazard ratio, 2.84; 95% CI, 1.37 to 5.89; p=0.0029). Steroid reduction was superior in the EC-MPS group (p=0.024). Adverse events did not differ between groups except for leukopenia in the AZA group.

Conclusion: EC-MPs was superior to AZA for treating active disease and preventing relapse in non-renal SLE patients.

Disclosure: J. Cortés-Hernández, None; L. Sáez-Comet, None; M. Pérez-Conesa, None; M. Rubio Rivas, None; F. Mitjavila, None; A. Castro Salomó, None; S. Parra, None; J. Cuquet Pedragosa, None; V. Ortiz-Santamaría, None; M. Mauri Plana, None; S. Bujan-Rivas, None; P. Suñé Martin, None; X. Vidal, None; J. Ordi-Ros, None.

To cite this abstract in AMA style:

Cortés-Hernández J, Sáez-Comet L, Pérez-Conesa M, Rubio Rivas M, Mitjavila F, Castro Salomó A, Parra S, Cuquet Pedragosa J, Ortiz-Santamaría V, Mauri Plana M, Bujan-Rivas S, Suñé Martin P, Vidal X, Ordi-Ros J. Enteric-Coated Mycophenolate Sodium Versus Azathioprine for Patients with Moderate/Severe Active Systemic Lupus Erythematosus: Results from a Phase 3, Randomized, Parallel, Multicentre Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/enteric-coated-mycophenolate-sodium-versus-azathioprine-for-patients-with-moderatesevere-active-systemic-lupus-erythematosus-results-from-a-phase-3-randomized-parallel-multicentre-study/. Accessed .

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