2255 - Initial Results for the LFA Collective Data Analysis Initiative (LFA CDAI): How Do Subjects From Lupus Clinical Trials Randomized to Standard of Care Respond Over Time?

Tuesday, November 8, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Kenneth C. Kalunian1, Mimi Kim2, Leslie M. Hanrahan3, Jean-Claude P. Becker4, Sabine Bongardt5, Paul Brunetta6, David Close7, Jorn Drappa7, Richard Furie8, Bevra H. Hahn9, Matthew Linnik10, Jane E. Salmon11, Neil Solomons12 and Joan T. Merrill13, 1UCSD School of Medicine, La Jolla, CA, 2Albert Einstein College of Medicine, Bronx, NY, 3Lupus Foundation of America, Washington, DC, 4Becker Clinical Reearch Consulting LLC, New York, NY, 5UCB Biosciences, 6Genentech, So San Francisco, CA, 7MedImmune Inc., 8North Shore-LIJ Health System, Lake Success, NY, 9UCLA David Geffen School of Medicine, Los Angeles, CA, 10Lilly Research Laboratories, 11Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, 12Vifor Pharma, 13Oklahoma Medical Research Foundation, Oklahoma City, OK
Presentation Number: 2255

Background/Purpose: In the past two decades, more than a dozen investigational products have entered phase II/III clinical trials for lupus and failed despite adequate proof of concept studies in animal models and in vitro human studies. The Lupus Foundation of America (LFA) formed the LFA Collective Data Analysis Initiative (CDAI) to better understand these failures. Working and steering committees were formed, comprised of academic and industry lupus experts and an independent biostatistician with lupus expertise. Industry partners contributed blinded and deidentified data from their clinical trials. The first LFA CDAI project was to address the hypothesis that in the course of clinical trials in lupus, background medications may mask the effect of an investigational agent. To understand response rates of different background medications, pooled data from 5 industry sponsored clinical trials in lupus were utilized.

Method: Data from the standard of care arms of 5 industry sponsored clinical trials (Total N=620) were combined to estimate response rates by background medication at different time points during follow up. Response was defined as an improvement by at least 1 step in any BILAG A and B at baseline without any new BILAG A. Background medications were classified into the following five groups: azathioprine (AZA), mycophenolate mofetil (MMF), methotrexate (MTX), cyclophosphamide (IVC), and other (including treatments such as antimalarials alone); corticosteroids usage was calculated for each treatment group. Separate subgroup analyses were also performed of nephritis patients only.  The chi-square test was used to evaluate the null hypothesis that response rates are equivalent across treatment groups. 

Result: Estimated response rates across background treatment groups ranged from 34%–65% at 12 weeks (p=0.06) and 28%–52% at 52 weeks (p=0.05). At both time points, the lowest response rate occurred in the MTX group. Mean steroid doses were 12.3–23.5mg at 12 weeks and 8.2–13.3 mg at 52 weeks and were significantly lower in responders compared to non-responders at 52 weeks (p=0.01) but not at 12 weeks (p=0.68). When the lupus nephritis trials were analyzed separately, using a more stringent response definition that required improvement in renal BILAG scores to C or better, response rates were 21% on IVC and 26% on MMF at 12 weeks and 34% on IVC and 42% on MMF at 24 weeks, the maximum duration of follow-up.

Conclusion: Lupus patients enrolled in clinical trials and randomized to standard of care arms are a proxy for real-life experiences of lupus patients who receive these standard therapies. The results of these analyses therefore provide a basis both for expected outcomes of lupus patients receiving standard of care in clinical practice and for lupus subjects in clinical trials randomized to these therapies. In addition, these data may be useful for investigators designing future clinical trials.

Keywords: clinical trials and systemic lupus erythematosus (SLE)

Disclosure: K. C. Kalunian, UCB, 2, UCB,Genentech, 5 ; M. Kim, None; L. M. Hanrahan, None; J. C. P. Becker, BMS, 3 ; S. Bongardt, UCB, 3 ; P. Brunetta, Genentech/, 3 ; D. Close, MedImmune, 3 ; J. Drappa, MedImmune, 3, Genentech and Biogen IDEC Inc., 3 ; R. Furie, Genentech and Biogen IDEC Inc., BMS, 5, UCB, 2 ; B. H. Hahn, None; M. Linnik, Biogen Idec, 3 ; J. E. Salmon, None; N. Solomons, Vifor, 3 ; J. T. Merrill, None.