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A phase 2 dose-ranging study of subcutaneous tabalumab for the treatment of patients with active rheumatoid arthritis and an inadequate response to methotrexate
  1. Mark C Genovese1,
  2. Eric Lee2,
  3. Julie Satterwhite3,†,
  4. Melissa Veenhuizen3,
  5. Damon Disch3,
  6. Pierre-Yves Berclaz3,
  7. Stephen Myers3,
  8. Gregory Sides3,†,
  9. Olivier Benichou3
  1. 1Division of Immunology and Rheumatology, Stanford University Medical Center, Palo Alto, California, USA
  2. 2Inland Rheumatology and Osteoporosis Medical Group, Upland, California, USA
  3. 3Eli Lilly and Company, Indianapolis, Indiana, USA †Deceased.
  1. Correspondence to Dr Mark Genovese, Stanford University Medical Center, Division of Immunology and Rheumatology, 1000 Welch Road #203, Palo Alto 94304, CA, USA; Genovese{at}Stanford.edu

Abstract

Objectives To assess the dose-response relationship, efficacy and safety of tabalumab, a human monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX).

Methods In this phase 2, 24-week, double-blind, placebo-controlled, dose-ranging study, patients with RA (N=158) on stable  MTX were randomised by Bayesian-adaptive method to receive 1, 3, 10, 30, 60, or 120 mg tabalumab or placebo subcutaneously every 4 weeks for 24 weeks. The primary objective was to test for a significant dose-response relationship using a statistical model of the proportion of patients having ≥50% improvement in American College of Rheumatology (ACR) criteria (ACR50) at week 24 (prespecified α=0.10).

Results At week 24, a significant dose-response relationship was observed using ACR50 (p=0.059) and ACR20 (p=0.044) response rates. Using model-estimated data, only 120 mg had significantly higher ACR50 and ACR20 response rates versus placebo (p<0.05). Observed response rates were significantly higher for 120 mg versus placebo as measured by ACR50 at weeks 12 (p=0.039) and 20 (p=0.018), but not week 24, and by ACR20 at weeks 12 (p=0.011) and 24 (p=0.039). Mean DAS28 C-reactive protein  improved with 120 mg at week 24 (p=0.048). Frequency of TEAEs was similar across groups (range 50–69%, p=0.884). Ten (8.2%) tabalumab and 5 (13.9%) placebo patients reported a serious adverse event (SAE). Infections occurred more frequently in patients exposed to tabalumab (30.3% vs 19.4%). Serious infections were reported in 3 (2.5%) tabalumab-treated patients only.

Conclusions A dose-response relationship was detected with monthly subcutaneous tabalumab. A significant effect was detected with the 120 mg dose with no unexpected safety signals.

Clinical Trial #NCT00785928.

  • Rheumatoid Arthritis
  • TNF-alpha
  • Autoimmune Diseases
  • B cells

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