A new study recently published in the journal Annals of the Rheumatic Diseases revealed the results of a Phase II trial assessing the use of the investigational therapeutic agent rontalizumab (rhuMAb interferon-alpha) in patients with systemic lupus erythematosus (SLE). The study was conducted by researchers at the University of California San Diego, the Oklahoma Medical Research Foundation and Genentech, and is entitled “A Phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-α) in patients with systemic lupus erythematosus (ROSE)”.
SLE is a severe autoimmune disease in which the body’s own immune system overreacts and uses autoantibodies to attack healthy joints and organs, resulting in inflammation, swelling, pain, disability and often in tissue destruction in multiple organs. High serum levels of interferon-alpha (IFN-alpha), an important molecule to protect the immune system, have been reported in SLE patients and associated to disease activity and flares.
Rontalizumab is a humanized monoclonal antibody against IFN-alpha developed by Genentech. The ROSE study (NCT00962832) was a randomized, multicenter, double-blind, placebo-controlled Phase II trial to assess the efficacy and safety of rontalizumab in patients with moderate-to-severe SLE. The trial enrolled 238 SLE patients in the United States, Latin America and Europe. Patients received either rontalizumab intravenously (750 mg) every 4 weeks (159 patients) or a placebo drug (79 patients). The clinical efficacy endpoints were the decrease in disease activity assessed by the British Isles Lupus Disease Activity Group (BILAG)-2004 (primary) and SLE response index (SRI, secondary) at 24 weeks after treatment. Rontalizumab efficacy was also evaluated by an exploratory measure of IFN-regulated gene expression (interferon signature metric, ISM).
Researchers found that 75.6% of SLE patients in the cohort had a high ISM. The efficacy response rates as determined by BILAG and SRI were found to be similar between patients under rontalizumab treatment and placebo. In the subgroup of patients with low ISM, however, the SRI response was found to be higher and steroid use lower in patients after 24 weeks of treatment with rontalizumab. In terms of safety, adverse effects were found to be comparable between rontalizumab and placebo groups.
The team concluded that rontalizumab treatment did not meet the ROSE clinical end points in patients with high ISM scores. On the other hand, SLE patients with low ISM scores (low IFN gene expression) were found to experience improved disease activity, flare reduction and decreased steroid use after treatment with rontalizumab, demonstrating a therapeutic benefit of the drug in a specific patient population. The authors suggest that further studies should be conducted to confirm these results in larger patient cohorts.