Phase II Clinical Trial Combining Abatacept and Cyclophosphamide for Lupus Nephritis Yields Poor Results

A clinical trial study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), and led by Dr. David Wofsy at University of California, San Francisco and Dr. Betty Diamond at Feinstein Institute for Medical Research, New York, assessed the efficacy of abatacept and cyclophosphamide combination therapy for lupus nephritis (ACCESS) treatment. The clinical trial identifier is NCT00774852 and is entitled “A Randomized, Double-blind, Controlled, Phase II Multicenter Trial of CTLA4Ig (Abatacept) Plus Cyclophosphamide vs Cyclophosphamide Alone in the Treatment of Lupus Nephritis.”

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease in which the body’s own immune system overreacts and attacks healthy joints and organs. When the immune system attacks the kidney in lupus patients, the organ suffers inflammation, a process also called lupus nephritis, which is one of the most severe complications in SLE patients, and if left untreated, can lead to long-term damage and even kidney failure.

“Euro-lupus” is a common therapy applied in the treatment of lupus nephritis, where patients are given three different medications – cyclophosphamide, azathioprine and prednisone – over several months. However, some patients were found to be non-responsive to this therapy, while others only exhibit a small improvement. In order to find an alternative therapy, the ACCESS clinical trial studied whether the addition of the drug abatacept to the standard Euro-lupus therapy in lupus patients could effectively improve lupus nephritis in comparison with Euro-lupus therapy alone.

Abatacept is a synthetic protein capable of blocking parts of the immune system responsible for the development of autoimmune diseases. Although it is considered an experimental medication in lupus, it is an FDA-approved treatment for rheumatoid arthritis.

The ACCESS trial was set as a double-blind, randomized, controlled phase II study with two experimental defined groups: abatacept plus Euro-lupus treatment and placebo plus Euro-lupus treatment. The study was performed between November 2008 and June 2014, and enrolled 137 individuals aged 16 and older from both genders with diagnosed SLE and active lupus nephritis.

The primary efficacy outcome of the trial was the frequency of complete response by week 24, referring to patients who successfully responded to treatment and had minimal activity of their lupus nephritis. The treatment was then continued up to week 52, although patients who had a complete response in the abatacept treatment group discontinued the therapy, allowing researchers to evaluate the potential of abatacept to sustain the clinical inactivity of lupus nephritis after stopping the immunosuppressive therapy. Regular physical examinations, blood and urine tests were performed on all participants.

Results from this clinical phase II trial were published in the journal Arthritis & Rheumatology entitled, “Treatment of Lupus Nephritis With Abatacept: The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study.”

At week 24, researchers found that 33% of the patients in the treatment group and 31% in the control group had a complete response to treatment, with no statistically significant difference. In terms of safety, no differences were reported. Of the patients who had a complete response at week 24 and underwent treatment without immunosuppressive therapy up to week 52, 50% maintained their complete response.

The team concluded that the addition of abatacept to the Euro-lupus therapy did not improve the outcome of lupus nephritis, suggesting that further investigations into alternative or complementary therapies for lupus nephritis should be conducted.