A phase 2 dose-ranging study of subcutaneous tabalumab for the treatment of patients with active rheumatoid arthritis and an inadequate response to methotrexate
| Autor: | Mark C. Genovese, Stephen L. Myers, Olivier Bénichou, Melissa Veenhuizen, Julie Satterwhite, Eric Lee, Gregory D. Sides, Damon Disch, Pierre-Yves Berclaz |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Health Status Injections Subcutaneous Immunology Drug Resistance Pilot Projects Placebo Antibodies Monoclonal Humanized Gastroenterology Severity of Illness Index General Biochemistry Genetics and Molecular Biology Arthritis Rheumatoid Young Adult Rheumatology Double-Blind Method Internal medicine Immunology and Allergy Medicine Humans Aged Dose-Response Relationship Drug business.industry Antibodies Monoclonal Middle Aged medicine.disease Dose-ranging study Connective tissue disease Surgery Clinical trial Tabalumab Methotrexate Treatment Outcome Rheumatoid arthritis Antirheumatic Agents Female Joints business medicine.drug |
| Zdroj: | Annals of the rheumatic diseases. 72(9) |
| ISSN: | 1468-2060 |
| Popis: | 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).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).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 (p0.05). 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.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. |
| Databáze: | OpenAIRE |
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