A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis
| Autor: | Pina M. Cardarelli, Allison Luo, Codrina Ancuta, Geoff Nichol, Andra Balanescu, Rodica Chirieac, Vira Tseluyko, Heidi N. Leblanc, Michael Yellin, Igor Paliienko, Li-An Xu, Semen Ter-Vartanian, Xiaolu Tao |
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| Rok vydání: | 2011 |
| Předmět: |
musculoskeletal diseases
Adult Male medicine.medical_specialty Immunology Placebo-controlled study Arthritis Pharmacology Placebo Antibodies Monoclonal Humanized Gastroenterology law.invention Arthritis Rheumatoid Rheumatology Randomized controlled trial Double-Blind Method law Internal medicine medicine Immunology and Allergy Humans Pharmacology (medical) Adverse effect Aged business.industry Middle Aged medicine.disease Chemokine CXCL10 Methotrexate Treatment Outcome Rheumatoid arthritis Antirheumatic Agents Drug Therapy Combination Female business medicine.drug |
| Zdroj: | Arthritis and rheumatism. 64(6) |
| ISSN: | 1529-0131 |
| Popis: | Objective CXCL10 (also known as interferon-γ–inducible 10-kd protein [IP-10]) is a chemokine that potentially plays a role in the immunopathogenesis of rheumatoid arthritis (RA). We undertook this phase II study to evaluate the efficacy and safety of MDX-1100, a fully human, anti-CXCL10 (anti–IP-10) monoclonal antibody, in RA patients whose disease responded inadequately to methotrexate (MTX). Methods Patients with active RA receiving stable doses of MTX (10–25 mg weekly) were randomized to receive intravenous doses of 10 mg/kg MDX-1100 (n = 35) or placebo (n = 35) every other week. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) on day 85, and patients were followed up for safety to day 141. Results The ACR20 response rate was significantly higher among MDX-1100–treated patients than among placebo-treated patients (54% versus 17%; P = 0.0024). Statistically significant differences in the ACR20 response rate between treatments were observed starting on day 43 (P < 0.05). The ACR50 and ACR70 response rates on day 85 did not differ between the groups. Overall, 51.4% of MDX-1100–treated patients and 30.3% of placebo-treated patients experienced at least 1 adverse event (AE). No study drug–related serious AEs were reported. Conclusion MDX-1100 was well tolerated and demonstrated clinical efficacy in RA patients whose disease responded inadequately to MTX. This is the first study to demonstrate clinical efficacy of a chemokine inhibitor in RA and supports the notion of a potential role of IP-10 in the immunopathogenesis of RA. |
| Databáze: | OpenAIRE |
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