Like rituximab, ocrelizumab selectively targets CD20-expressing B cells. Elimination of these cells interferes with the inflammatory cascade that leads to the symptoms of rheumatoid arthritis. Ocrelizumab is humanised rather than chimaeric; therefore, it is expected to be less immunogenic than rituximab.
STAGE included 1015 seropositive patients who had an inadequate response to methotrexate. Investigators randomised patients to receive two intravenous 200mg or 500mg infusions of ocrelizumab or placebo over two weeks, in addition to weekly methotrexate. Infusions were repeated after 6 months.
Compared with patients who received methotrexate and placebo, those treated with methotrexate plus ocrelizumab showed improvements in signs and symptoms of their disease at weeks 24 and 48. Improvement was defined as a 20% reduction in joint swelling and tenderness according to American College of Rheumatology criteria (ACR20).
Adverse effects were generally comparable between the ocrelizumab and placebo groups patients, although serious infections were more common in the ocrelizumab-treated patients.
Concerns about opportunistic infections led researchers to suspend dosing of some patients in STAGE, as well as in two other Phase III studies of ocrelizumab in rheumatoid arthritis: FEATURE and SCRIPT. A fourth rheumatoid arthritis trial, FILM, was put on clinical hold by the FDA.
FEATURE is testing a single infusion of ocrelizumab, rather than the standard double infusion. SCRIPT enrolled patients with an inadequate response to TNF-α inhibitors, and FILM recruited methotrexate-naïve individuals. Results from these three trials are expected to be released in the first half of 2010 by Genentech and Biogen Idec, joint developers of ocrelizumab.