Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study
| Autor: | Stevan Shaw, Sophie Glatt, Dominique Baeten, Foteini Strimenopoulou, Iain B. McInnes, Georg Schett, Robert Landewé, Mark I L Watling, Lucian Ionescu, Peter C. Taylor |
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| Přispěvatelé: | Clinical Immunology and Rheumatology, AII - Inflammatory diseases |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Severity of Illness Index Gastroenterology Arthritis Rheumatoid 0302 clinical medicine Immunology and Allergy Certolizumab pegol treatment Incidence (epidemiology) Remission Induction Middle Aged Treatment Outcome Antirheumatic Agents Rheumatoid arthritis Monoclonal Drug Therapy Combination Female Patient Safety medicine.drug Adult medicine.medical_specialty Maximum Tolerated Dose Immunology Rheumatoid Arthritis anti-tnf Antibodies Monoclonal Humanized Placebo Risk Assessment Loading dose Drug Administration Schedule General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Double-Blind Method Rheumatology Internal medicine medicine Humans DAS28 In patient Adverse effect 030203 arthritis & rheumatology Dose-Response Relationship Drug business.industry dmards (biologic) medicine.disease 030104 developmental biology Certolizumab Pegol business |
| Zdroj: | Annals of the Rheumatic Diseases Annals of the rheumatic diseases, 78(8), 1033-1040. BMJ Publishing Group |
| ISSN: | 0003-4967 |
| DOI: | 10.1136/annrheumdis-2018-214943 |
| Popis: | ObjectiveEvaluate the efficacy and safety of dual neutralisation of interleukin (IL)-17A and IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) and inadequate response (IR) to certolizumab pegol.MethodsDuring this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), patients with moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 and 4, and 200 mg at Week 6. Patients with IR at Week 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))>3.2) were randomised 2:1 to CZP (200 mg every 2 weeks (Q2W)) plus bimekizumab (240 mg loading dose then 120 mg Q2W) or CZP plus placebo. The primary efficacy and safety variables were change in DAS28(CRP) between Weeks 8 and 20 and incidence of treatment-emergent adverse events (TEAEs).ResultsOf 159 patients enrolled, 79 had IR at Week 8 and were randomised to CZP plus bimekizumab (n=52) or CZP plus placebo (n=27). At Week 20, there was a greater reduction in DAS28(CRP) in the CZP-IR plus bimekizumab group compared with the CZP-IR plus placebo group (99.4% posterior probability). The most frequent TEAEs were infections and infestations (CZP plus bimekizumab, 50.0% (26/52); CZP plus placebo, 22.2% (6/27)).ConclusionsPoC was confirmed based on the rapid decrease in disease activity achieved with 12 weeks of CZP plus bimekizumab. No unexpected or new safety signals were identified when neutralising IL-17A and IL-17F in patients with RA concomitantly treated with CZP, but the rate of TEAEs was higher with dual inhibition. |
| Databáze: | OpenAIRE |
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