A multicentre, randomised controlled study of enteric-coated mycophenolate sodium for the treatment of relapsed or resistant proliferative lupus nephritis: an Asian experience Sirirat Anutrakulchai, 1 Thanachai Panaput, 2 Jeerapat Wongchinsri, 3 Somchai Chaishayanon, 3 Bancha Satirapoj, 4 Opas Traitanon, 5 Warabhorn Pima, 6 Chutima Rukrung, 7 Bandit Thinkhamrop, 8 Yingyos Avihingsanon, 9,10 for the CONTROL-Lupus study group To cite: Anutrakulchai S, Panaput T, Wongchinsri J, et al. A multicentre, randomised controlled study of enteric-coated mycophenolate sodium for the treatment of relapsed or resistant proliferative lupus nephritis: an Asian experience. Lupus Science & Medicine 2016;3:e000120. doi:10.1136/lupus-2015- 000120 ▸ Additional material is available. To view please visit the journal (http://dx.doi.org/ 10.1136/lupus-2015- 000120). Received 31 July 2015 Revised 26 November 2015 Accepted 13 December 2015 For numbered affiliations see end of article. Correspondence to Professor Yingyos Avihingsanon; Yingyos.a@gmail.com ABSTRACT Objective: The optimal treatment of relapse or resistant lupus nephritis (LN) is still unclear. Mycophenolate might be an alternative therapy to avoid toxicities of cyclophosphamide (CYC). This study was aimed to compare enteric-coated mycophenolate sodium (EC- MPS) versus intravenous CYC as an induction therapy. Methods: The study was a 12-month period of multicentre, open-labelled randomised controlled trial. Fifty-nine patients who had relapsed (36%) or who were resistant to previous CYC treatment (64%) and all who were biopsy-proven class III/IV, were randomised into CYC (n=32) and EC-MPS groups (n=27). The CYC group received intravenous CYC 0.5–1 g/m 2 monthly and the EC-MPS group was treated with EC-MPS 1440 mg/day for first 6 months. After induction therapy, both groups received EC-MPS 720 mg/day until the end of study at 12 months. Results: The study was prematurely terminated due to high rate of serious adverse events in CYC arm. Death and serious infections were observed more in the CYC group (15.6% in CYC and 3.5% in EC-MPS; p=0.04). The early discontinuation rates, mainly from serious infections, were significantly higher in CYC group (percentage differences of 16.9; 95% CI 1.3 to 32.4). At the 12th month, both arms were comparable in terms of complete and partial remission rates (68% CYC and 71% EC-MPS) and times to remission (96 days CYC and 97 days EC-MPS). Composites of unfavourable outcomes (death, doubling of serum creatinine, non-remission and intolerance to treatment) were 46.9% and 37% in CYC and EC-MPS (risk difference=9.84; p=0.44). Conclusions: EC-MPS may have comparable efficacy, but was better tolerated than CYC. EC-MPS should be an alternative choice of treatment for difficult-to-treat LN, particularly in CYC-experienced LN patients. Due to an early termination of the study, further clinical implementation could be cautiously used. Trial registration number: Clinicaltrials.gov ID#NCT01015456. INTRODUCTION Lupus nephritis (LN) is the leading cause of chronic glomerulonephritis and could rapidly develop into an end-stage renal disease. 1–3 It is a common and severe form in patients with systemic lupus erythematosus among those of Asian ethnicity. 4–7 The proliferative LN (the International Society of Nephrology and the Renal Pathology Society (ISN/RPS) class III/ IV) is common and has the worst progno- sis. 28–11 Relapse and resistance to therapy are the grave prognostic factors. 3 12–15 Although cyclophosphamide (CYC) is an effective treat- ment of choice, cumulative toxicities are its main limitation in repeated administration. In real-life practice, many patients were previ- ously treated with CYC, and they have a relapse or have received certain dosages of CYC without improvement. In these so-called difficult-to-treat cases, patients were similarly exposed to steroids, CYC and other immunosuppressants. Two forms of mycophenolic acid drugs including mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) are available. MMF was proven effective for the treatment of active LN in both KEY MESSAGES ▸ For difficult-to-treat LN, there is minimal evi- dences for the optimal treatment. ▸ Treatment with intravenous cyclophosphamide and steroids could increase risks of infection- related mortality in this setting. ▸ Enteric-coated mycophenolate sodium could be an alternative treatment of choice for this condi- tion in Asian patients. Anutrakulchai S, Panaput T, Wongchinsri J, et al. Lupus Science & Medicine 2016;3:e000120. doi:10.1136/lupus-2015-000120 1 Lupus nephritis