Discontinued for RA, Tabalumab Looks Good in Extension Trial

September 11, 2014

The B-cell depleter tabalumab proved effective in a long-term trial, but only after its maker had stopped development for rheumatoid arthritis.

Greenwald M, Szczepanski L, Kennedy, A, et al. A 52-week, open-label study evaluating the safety and efficacy of tabalumab, an anti-B-cell activating factor monoclonal antibody, for rheumatoid arthritis.  Arthritis Research & Therapy (2014) 16:415. doi:10.1186/s13075-014-0415-2. (Open access.)

The anti B-cell activator tabalumab proves effective in a multinational Phase 2 extension study in rheumatoid arthritis (RA) -- reducing disease activity and improving function -- more than a year after disappointing results put the brakes on clinical trials in RA.

In the 52-week open-label extension, 182 patients finishing one of two earlier randomized trials received monthly subcutaneous 60 mg tabalumab for 12 weeks, then a doubled dose for 48 weeks with a one-time option to step down to the original dose.

More than two-thirds ending up on 60 mg (n=60) and those in the 120 mg group (n=121) achieved a 20% or greater improvement in American College of Rheumatology criteria (ACR20) by two months, maintaining that for one year, the researchers report. Both groups also show efficacy at ACR50 and ACR70 levels.

A majority of patients in the 60 mg group (84%) and half of those in the 60/120 mg group achieved good or moderate responses by European League Against Rheumatism responder index in 28 joints (EULAR28).

Pre-tabalumab disease activity had been higher in the 60/120 mg group. At one year, both dose groups had lower Disease Activity in 28 joints C-reactive protein (DAS28-CRP) and reduced disability in the Health Assessment Questionnaire-Disability Index (HAQ-DI). All had declines in B-cells, but not total depletion.

Nearly two-thirds (73%) reported adverse events (AEs), with more serious AEs in the 60/120 mg group. AEs included infections, worsening of RA, myocardial ischemia, and disc inflammation. Five percent of patients in each group discontinued due to an AE. The single death in the 60/120 mg group was unrelated to treatment.

In February 2013, lack of efficacy in later Phase 3 trials prompted Eli Lilly and company to stop development of tabalumab for RA and discontinue ongoing trials. However, Phase 3 studies in systemic lupus erythematosus (SLE) continue.