Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Abatacept for Lupus Nephritis: Alternative Outcome Measures Support Opposing Interpretations of Data From a Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II/III Study.
Wofsy1, David, Shropshire2, Stephanie Meadows, Hillson3, Jan L., Diamond4, Betty
VA Medical Center, San Francisco, CA
Bristol-Myers Squibb, Richmond, VA
ZymoGenetics Inc., Seattle, WA
Feinstein Institute Med Rsch, Manhasset, NY
Background/Purpose:
Recent trials of novel therapies for lupus nephritis (LN) have used varying primary endpoints, but there is no consensus about which may be most sensitive to change or most representative of clinical status. We compared the performance of two different outcome measures when applied to the same data set from a double-blind, controlled phase II/III study of abatacept (ABA) in patients with LN (trial IM101075- efficacy and safety reported in a separate abstract).
Methods:
In IM101075, 300 subjects were randomized 1:1:1 to one of: 3 mos ABA 30 mg/kg and 9 mos of 10 mg/kg [30/10]; 12 mos ABA10 mg/kg [10/10]; or placebo, administered IV in combination with MMF (target dose 1.5–3.0 gm/d) and corticosteroids (prednisone 60 mg/d or equivalent with response-guided taper.) We compared two outcome measures (OM) that have been accepted by the FDA for use in trials of ABA for LN. OM1, from IM101075, is the proportion of subjects with complete response (CR) at Study Day 337 and 365, defined as eGFR within 10% of pre-treatment value, urine prot:creat ratio (UPCR) <30 mg/mmol, and normal urine sediment. In contrast, OM2 as defined in the ongoing ACCESS study (NCT00774852) is the proportion of subjects who reach CR,defined as serum creatinine either normal or <=125% of baseline, UPCR <0.5 g/g, and prednisone dose <=10 mg/d at Study Day 365; urine sediment is not a component of OM2. In 24 subjects from IM101075, renal disease was too mild at entry (UPCR <1 g/g) to apply the OM2 criteria; therefore, these subjects were excluded from the analysis of OM2.
Results:
The analysis of OM1 in study IM101075 showed few CRs overall and no difference among the groups (Table). In contrast, OM2 yielded a much higher CR rate and significant differences among groups. The results with OM2 were most striking in patients who were nephrotic at baseline (UPCR >339 mg/mmol).
Conclusion:
These findings demonstrate the importance of the choice of outcome measure for LN trials, and they strongly suggest that OM2 is more sensitive to differences between groups. The ability of either measure to predict long-term outcome remains to be determined. These findings have implications for the interpretation of the IM101075 study from which the data were drawn, supporting further evaluation of the efficacy ABA+MMF in patients with LN.
To cite this abstract, please use the following information:
Wofsy, David, Shropshire, Stephanie Meadows, Hillson, Jan L., Diamond, Betty; Abatacept for Lupus Nephritis: Alternative Outcome Measures Support Opposing Interpretations of Data From a Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II/III Study. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2474
DOI:
