In the Journals

Tabalumab fails phase 3 trial in patients with rheumatoid arthritis

Tabalumab did not meet its primary endpoints in a phase 3 trial of patients with rheumatoid arthritis, according to the recently published results of a study.

Researchers enrolled 456 patients into the randomized, double-blind, placebo-controlled study. Patients were diagnosed with rheumatoid arthritis (RA) using American College of Rheumatology (ACR) criteria and were placed in functional class I, II or III and had at least eight of 68 tender and at least eight of 68 swollen joints. All had a history of poor response to treatment with at least one tumor necrosis factor (TNF) inhibitor. The mean patient age was 53 years, 84% were women, and mean disease duration was 8.2 years. About three-quarters of the patients were seropositive with rheumatoid factor and anti-cyclic citrullinated peptide antibodies.

About half of the patients completed the trial. At week 24, 76 patients (49.7%) in the 120-mg group, 76 patients (51.4%) in the 90-mg group and 69 patients (44.5%) in the placebo group remained in the study, and three, five and seven patients completed 48-week follow-up, respectively.

Patients were randomized to 120-mg subcutaneous tabalumab (Eli Lilly) every 4 weeks (n = 153), 90-mg every 2 weeks (n = 148) or placebo (n = 155).

At 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). An ACR20 response rate was higher at week 12 but the improvements were not sustained.

Both treatment groups had an increase in mean CD20+ B cells at week 1 and, excluding non-responders, CD20+ B cells were reduced by a median 43.2% in the 120-mg group, by 53.2% in the 90-mg group and by 1.1% in the placebo group. Nonresponders showed similar changes in B cell counts. Patients in the treatment groups also showed lower levels of immunoglobulins at 24 weeks.

Adverse events included infections occurring at similar rates among the three groups and included infections, injection site reactions and general disorders. Serious adverse events were reported in seven patients in the 120 mg group, and six each in 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 wrote. “Targeting B-cell activating factor may not be a viable therapeutic approach.” – by Shirley Pulawski

Disclosure: Schiff reports consultancy fees with AbbVie, Amgen, Antares, Bristol-Myers Squibb, Eli Lilly, Horizon, Johnson & Johnson, Novartis, Novo Nordisk, Pfizer, Roche and UCB Pharma; he is a member of AbbVie’s speaker bureau; and has received research funding from UCB Pharma. Please see the full study for a list of all other authors’ relevant financial disclosures.

Tabalumab did not meet its primary endpoints in a phase 3 trial of patients with rheumatoid arthritis, according to the recently published results of a study.

Researchers enrolled 456 patients into the randomized, double-blind, placebo-controlled study. Patients were diagnosed with rheumatoid arthritis (RA) using American College of Rheumatology (ACR) criteria and were placed in functional class I, II or III and had at least eight of 68 tender and at least eight of 68 swollen joints. All had a history of poor response to treatment with at least one tumor necrosis factor (TNF) inhibitor. The mean patient age was 53 years, 84% were women, and mean disease duration was 8.2 years. About three-quarters of the patients were seropositive with rheumatoid factor and anti-cyclic citrullinated peptide antibodies.

About half of the patients completed the trial. At week 24, 76 patients (49.7%) in the 120-mg group, 76 patients (51.4%) in the 90-mg group and 69 patients (44.5%) in the placebo group remained in the study, and three, five and seven patients completed 48-week follow-up, respectively.

Patients were randomized to 120-mg subcutaneous tabalumab (Eli Lilly) every 4 weeks (n = 153), 90-mg every 2 weeks (n = 148) or placebo (n = 155).

At 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). An ACR20 response rate was higher at week 12 but the improvements were not sustained.

Both treatment groups had an increase in mean CD20+ B cells at week 1 and, excluding non-responders, CD20+ B cells were reduced by a median 43.2% in the 120-mg group, by 53.2% in the 90-mg group and by 1.1% in the placebo group. Nonresponders showed similar changes in B cell counts. Patients in the treatment groups also showed lower levels of immunoglobulins at 24 weeks.

Adverse events included infections occurring at similar rates among the three groups and included infections, injection site reactions and general disorders. Serious adverse events were reported in seven patients in the 120 mg group, and six each in 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 wrote. “Targeting B-cell activating factor may not be a viable therapeutic approach.” – by Shirley Pulawski

Disclosure: Schiff reports consultancy fees with AbbVie, Amgen, Antares, Bristol-Myers Squibb, Eli Lilly, Horizon, Johnson & Johnson, Novartis, Novo Nordisk, Pfizer, Roche and UCB Pharma; he is a member of AbbVie’s speaker bureau; and has received research funding from UCB Pharma. Please see the full study for a list of all other authors’ relevant financial disclosures.