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AB0438 Efficacy and Safety of Tabalumab, an Anti-B Cell Activating Factor Monoclonal Antibody, in Patients with Rheumatoid Arthritis WHO HAD an Inadequate Response to Tnf-Alpha Inhibitors: Results from A Phase 3 Multicenter, Randomized, Double-Blind Study
  1. M. Schiff1,
  2. B. Combe2,
  3. T. Dörner3,
  4. J.M. Kremer4,
  5. T.W. Huizinga5,
  6. M. Veenhuizen6,
  7. A. Gill6,
  8. H. Zou7,
  9. W. Komocsar6,
  10. P.-Y. Berclaz6,
  11. R. Ortmann6,
  12. C. Lee6
  1. 1University of Colorado, Denver, United States
  2. 2Hospital of Lapeyronie and University of Montpellier, Montpellier, France
  3. 3Charité–Universitätsmedizin Berlin, Berlin, Germany
  4. 4Albany Medical College, Albany, United States
  5. 5Leiden University Medical Center, Leiden, Netherlands
  6. 6Eli Lilly and Company, Indianapolis
  7. 7inVentiv Health, Atlanta, United States

Abstract

Background Tabalumab is a monoclonal antibody that neutralizes membrane-bound and soluble B cell activating factor (BAFF).

Objectives Evaluate efficacy and safety of tabalumab, in RA pts who had an inadequate response to ≥1 TNF-a inhibitors, in a randomized, double-blinded, placebo-controlled study.

Methods 456 pts with active RA were enrolled in this 24-wk study evaluating 2 different subcutaneous (SQ) tabalumab doses (120mg every 4 wks [120/Q4W] or 90mg every 2 wks [90/Q2W]) vs placebo (PBO). At wk 0, pts received a SQ loading dose that was 2 times the planned treatment dose (ie, 240mg, 180mg, or PBO). Eligible pts included those receiving background DMARDs and having previously discontinued TNF-a inhibitor therapy due to lack of efficacy or intolerance. The primary efficacy endpoint was ACR20 at 24 wks; secondary efficacy endpoints included ACR50, change in DAS28-CRP and change in HAQ-DI at 24 wks. This study was terminated early due to futility.

Results At baseline, the study population was mostly female (83.6%) and seropositive (RF and/or anti-CCP, 92%), with a mean age of 53.2 yrs, mean RA diagnosis of 8.2 yrs, and moderate to high disease activity DAS28-CRP of 5.9±1.0 (mean ± SD). At wk 24, there were no significant differences among the 120/Q4W, 90/Q2W, and PBO groups in the percentage of pts who achieved ACR20 (NRI; 17.6%, 24.3%, 20.0%) and ACR50 (NRI; 7.2%, 5.4%, 3.9%), and no significant differences in DAS28-CRP (mBOCF; 5.1±1.5, 5.1±1.5, 5.2±1.4; mean ± SD), or HAQ-DI (mBOCF; 1.5±0.7, 1.6±0.7, 1.6±0.7; mean ± SD). After 24 wks, changes in CD3-CD20+ B cells in the 120/Q4W, 90/Q2W, and PBO groups were generally consistent with prior phase 2 results (−10.8%, −9.6%, and 10.9%), as were changes in immunoglobulin levels: IgM (−15.0%, −14.8%, 0.2%), IgA (−9.0%, −9.0%, 1.6%), and IgG (−7.2%, −7.9%, 1.4%).

Safety was evaluated in all randomized pts who received ≥1 dose of study treatment (n=454). Discontinuations due to an AE were similar across the 120/Q4W, 90/Q2W, and PBO groups (2.6%, 2.7%, 2.6%) as were TEAEs (59.5%, 51.7%, 51.9%) and SAEs (4.6%, 4.1%, 3.9%). For the 120/Q4W, 90/Q2W, and PBO groups, AEs of interest were infections (24%, 26%, 23%); injection-site reactions (2.6%, 4.8%, 0.0%); and allergic/hypersensitivity events (3.9%, 4.1%, 3.9%). There were no differences between groups in reports of opportunistic infections, tuberculosis, or serious infection events. No deaths occurred.

Conclusions In this phase 3 study, tabalumab demonstrated no clinical efficacy despite evidence of biologic activity, suggesting that targeting BAFF may not be a viable therapeutic approach to treating pts with RA. There were no differences in reports of infection or allergic/hypersensitivity events and no new or unexpected safety findings for RA pts receiving tabalumab.

Disclosure of Interest M. Schiff Consultant for: Eli Lilly and Company, B. Combe Grant/research support: Pfizer, Roche-Chugai, Speakers bureau: Eli Lilly and Company, BMS, Merck, Pfizer, Roche-Chugai, UCB, T. Dörner Grant/research support: Roche-Chugai, Sanofi-Aventis, Janssen, UCB, Consultant for: Eli Lilly and Company, Roche-Chugai, UCB, Speakers bureau: Roche-Chugai, UCB, J. Kremer Grant/research support: Eli Lilly and Company, Consultant for: Eli Lilly and Company, T. Huizinga Consultant for: Eli Lilly and Company, M. Veenhuizen Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, A. Gill Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, H. Zou: None declared, W. Komocsar Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, P.-Y. Berclaz Employee of: Eli Lilly and Company, R. Ortmann Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, C. Lee Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company

DOI 10.1136/annrheumdis-2014-eular.3305

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