Mycophenolate sodium superior to azathioprine in lupus patients
Enteric-coated mycophenolate sodium (EC-MPS) appears to be more effective than azathioprine (AZA) at inducing long-term clinical remission and preventing relapse in patients with active systemic lupus erythematosus (SLE), according to the results of an open-label trial.
A total of 240 patients were randomized to receive either EC-MPS at 1,440 mg/day (n=120; mean age 42.1 years; 90 percent female) or AZA at 2/mg/kg/day (n=120; mean age 40.9 years; 92.5 percent female) in addition to prednisone and/or antimalarials. Treatment lasted 24 months.
The primary endpoint of the proportion of patients achieving clinical remission (SLE Disease Activity Index 2000=0) was found to be greater in the EC-MPS than in the AZA arm at months 3 (32.5 vs 19.2 percent; treatment difference, 13.3; 95 percent CI, 2.3 to 24; p=0.034) and 24 (71.2 vs 48.3 percent; treatment difference, 22.9; 10.4 to 34.4; p<0.001). [Ann Rheum Dis 2017;doi:10.1136/annrheumdis-2016-210882]
EC-MPS also showed superiority in terms of relapse prevention. The occurrence of British Isles Lupus Assessment Group (BILAG) flares was less frequent when compared to AZA (BILAG A/B [moderate-to-severe]: 50 vs 71.7 percent; p=0.001; BILAG B [moderate]: 8.3 vs 21.67 percent; p=0.004).
Researchers said EC-MPS reduced the risk of developing any SLE flare and severe flare by 45 and 65 percent, respectively.
Moreover, time to clinical remission (hazard ratio [HR], 1.43; 1.07 to 1.91; p=0.017) and time to first BILAG A/B flare (HR, 1.81; 1.3 to 2.56; p=0.0004) and BILAG A flare (HR, 2.84; 1.37 to 5.89; p=0.003) were better with EC-MPS vs AZA.
In terms of safety, “[t]he occurrence of AEs [59.2 vs 57.5 percent with EC-MPS and AZA, respectively] and serious events [serious infections, 4.2 vs 5.8 percent] was similar in both groups except for gastrointestinal side effects, including liver toxicity, and haematological events, which were more common in the AZA group, consistent with previous findings,” researchers noted. [Rheumatology 2010;49:723–32; N Engl J Med 2011;365:1886–95; Ann Rheum Dis 2010;69:2083–9]
A chronic multisystem autoimmune disease, SLE is characterised by heterogeneous clinical manifestations and a relapsing–remitting course. The present data indicate that EC-MPS is superior to AZA, which is one of the most frequently used immunosuppressants, in achieving long-term clinical remission and in preventing relapse in patients with active nonrenal lupus disease, they said. [N Engl J Med 2008;358:929–39]
“Despite AZA being shown to be less effective, its safety profile during pregnancy is a significant advantage over EC-MPS. Mycophenolate mofetil [MMF] and EC-MPS are absolutely contraindicated,” they continued.
“MMF is likely to be a human teratogen based on the reported malformations observed among exposed offspring (microtia, orofacial clefts, external auditory canal atresia and cardiovascular malformations). When long-term immunosuppression is required in young women planning pregnancy this issue needs to be considered,” they said. [Am J Med Genet A 2009;149A:1241–8]
Researchers cited several study limitations, such as the inclusion of mainly Caucasian patients rather than a large international multiethnic population, the open-label design, and the failure to routinely perform serum measures of the active metabolites of AZA or EC-MPS.