Design flaws hamper lupus nephritis biologic trials

Failure of abatacept lupus nephritis trial

The failure of another recent trial to show any benefit of abatacept in treating refractory lupus nephritis could also be related to the problem of inconsistent trial endpoints making it difficult to compare therapies (Arthritis Rheum. 2012;64:3660-5). For instance, urine protein-creatinine ratios (UPCRs) are subject to individual variability but the criteria for UPCRs have varied from 0.2 to 0.5 in different lupus nephritis trials, including this abatacept trial, the LUNAR trial, the Aspreva Lupus Management Study (ALMS), and the Abatacept and Cyclophosphamide Combination Therapy for Lupus Nephritis (ACCESS) trial, as well as in the ACR’s recommendations for lupus nephritis.

Estimated glomerular filtration rate (eGFR) criteria also are inconsistent, and endpoints that refer to "normal" eGFRs are hard to interpret, Dr. Rovin said, because it is unclear what is normal for creatine "unless the patient’s true serum creatinine before SLE is known."

"We need uniform, reasonable and consistent response criteria for lupus nephritis clinical trials, and these responses should be associated with long-term outcomes," said Dr. Rovin, who noted that he is involved in preparing a white paper on clinical trial design for lupus nephritis.

Dr. Rovin has served as a consultant to Bristol-Myers Squibb, which markets abatacept, as well as Biogen Idec and Genentech, which comarket rituximab in the United States. He has also received honoraria from Biogen Idec and Genentech and research funding from Roche, Genentech’s parent company.