Long-term safety and efficacy of sarilumab over 5 years in patients with rheumatoid arthritis refractory to TNF inhibitors
| Autor: | Karina Maslova, A. Praestgaard, H. Leher, Gerd R Burmester, Roy Fleischmann, Mark C. Genovese |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Neutropenia Drug-Related Side Effects and Adverse Reactions Long Term Adverse Effects Antibodies Monoclonal Humanized Infections Placebo law.invention Arthritis Rheumatoid Double-Blind Method Rheumatology Randomized controlled trial law Internal medicine Product Surveillance Postmarketing Humans Medicine Pharmacology (medical) Adverse effect Dose-Response Relationship Drug Drug Tapering business.industry Middle Aged medicine.disease Receptors Interleukin-6 Discontinuation Sarilumab Treatment Outcome Antirheumatic Agents Rheumatoid arthritis Absolute neutrophil count Female Drug Monitoring business |
| Zdroj: | Rheumatology. 60:4991-5001 |
| ISSN: | 1462-0332 1462-0324 |
| Popis: | Objective The objective of this study was to evaluate the long-term safety and efficacy of sarilumab over 5 years in patients with RA refractory to TNF inhibitors (TNFis). Methods Patients in the 24-week randomized controlled trial (RCT) TARGET (NCT01709578) who received double-blind placebo or sarilumab 150 or 200 mg every 2 weeks (q2w), plus conventional synthetic DMARDs (csDMARDs), were eligible to receive open-label sarilumab 200 mg q2w plus csDMARDs in the open-label extension (OLE), EXTEND (NCT01146652). OLE dose reduction to 150 mg q2w was permitted per investigators’ judgement or protocol-mandated safety concerns. Safety and efficacy were assessed through treatment-emergent adverse events (AEs), laboratory abnormalities and clinical DASs. All statistics are descriptive. Results Of 546 patients, 454 (83%) were treated with sarilumab in the OLE. The cumulative observation period was 1654.8 patient-years (PY; n = 521); 268 patients (51%) had ≥4 years’ exposure. Incidence rates per 100 PY of AEs, and AEs leading to discontinuation, infection and serious infection were 160.4, 8.1, 57.8 and 3.9, respectively. Neutropenia was the most common AE (15.3 per 100 PY). An absolute neutrophil count of 1 TNFi failure, and similar for patients who either remained on 200 mg or reduced to 150 mg. Conclusion In patients with RA refractory to TNFi, sarilumab’s long-term term safety profile was consistent with previous clinical studies and post-marketing reports. Efficacy was sustained over 5 years. Trial registration TARGET, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01709578, NCT01709578; EXTEND, ClinicalTrials.gov, https://www.clinicaltrials.gov/ct2/show/NCT01146652, NCT01146652. |
| Databáze: | OpenAIRE |
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