Tabalumab, an anti-B Cell Activating Factor (BAFF) monoclonal antibody, which has been designed to treat autoimmune disorders and B-cell malignancies, by Eli Lilly and Company, did not meet its primary endpoints in a phase III clinical trial destined to observe the drug’s effects in patients with rheumatoid arthritis (RA). Previously, two other clinical trials, a phase III trial for RA patients (February 2013) and one for SLE patients (September 2014) had also been terminated due to similar reasons.
For this particular randomized, double-blind, placebo-controlled trial, a total of 456 patients were enrolled after being diagnosed with RA, according to the American College of Rheumatology (ACR) criteria. They had at least eight of 68 tender and swollen joints, with all patients presenting a history of poor response to treatment with at least one tumor necrosis factor (TNF) inhibitor. Mean patient age was of 53 years, 84% of the subjects were women and mean disease duration was of 8.2 years. Laboratory test reports revealed seventy five percent of these patients were seropositive with rheumatoid factor and anti-cyclic citrullinated peptide antibodies.
Patients were randomized to 120-mg subcutaneous tabalumab every 4 weeks (n = 153), 90-mg every 2 weeks (n = 148) or placebo (n = 155). By the end of the trial around half of the patients survived the study. At the end of 12 weeks of treatment, patients were seen to respond well to treatment, but this could not be sustained in the following weeks. At the end of week 24 17.6% of patients in the 120-mg group, 24.3% of the 90-mg group and 20% of patients in the placebo group responded with an improvement of 20% (ACR20).
In the beginning of the study, both groups who received 120mg and 90mg of the drug and those on placebo had an increase in the average of CD20+ B cell population during week 1, which declined 43.2% in the 120-mg group, 53.2% in the 90-mg group and 1.1% in the placebo group upon treatment initiation. Non-responders also showed similar changes in B cell counts and all patients had lower levels of immunoglobulin by week 24.
In all three groups the most common adverse effects included infections, injection site reactions and general disorders. Serious adverse events were reported in seven patients in the 120 mg group, and in six of the 90 mg and placebo groups.
“In patients with prior inadequate response to TNF inhibitors, targeting the B-cell activating factor pathway alone was not an effective approach to treating RA,” the researchers concluded. “Targeting B-cell activating factor may not be a viable therapeutic approach,” they further added.