Academic Journal
POS0268 INTRAVENOUS TOCILIZUMAB FOR THE TREATMENT OF GIANT CELL ARTERITIS: A PHASE IB DOSE-RANGING PHARMACOKINETIC BRIDGING STUDY
| العنوان: | POS0268 INTRAVENOUS TOCILIZUMAB FOR THE TREATMENT OF GIANT CELL ARTERITIS: A PHASE IB DOSE-RANGING PHARMACOKINETIC BRIDGING STUDY |
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| المؤلفون: | Schmitt, C., Brockwell, L., Giraudon, M., Zucchetto, M., Christ, L., Bannert, B., Daikeler, T., Villiger, P. |
| المصدر: | Annals of the Rheumatic Diseases ; volume 81, issue Suppl 1, page 376.2-377 ; ISSN 0003-4967 1468-2060 |
| بيانات النشر: | BMJ |
| سنة النشر: | 2022 |
| الوصف: | Background Subcutaneous (SC) tocilizumab (TCZ), a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, is approved globally for the treatment of giant cell arteritis (GCA), with once weekly injections, based on the GiACTA trial. Objectives This Phase Ib study ( NCT03923738 ) investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety and exploratory efficacy of 2 doses of TCZ given intravenously (IV) in patients with GCA. The purpose was to explore an IV dose resulting in a minimum exposure level within the range of effective trough concentrations achieved with TCZ SC dosing in GCA and not exceeding the exposure of the well-tolerated 8 mg/kg IV every 4 weeks (Q4W) in rheumatoid arthritis (RA). Methods This study enrolled patients with GCA in Switzerland who had received ≥5 consecutive doses of TCZ IV 8 mg/kg (off label) Q4W and were in remission. Patients received 5 or 6 doses of TCZ IV 7 mg/kg Q4W in period 1 and, if still in remission, then received 5 or 6 doses of 6 mg/kg Q4W in period 2. Glucocorticoid use was at the investigator’s discretion. PK endpoints were maximum concentration (C max ), minimum (trough) concentration (C trough ), area under the curve (AUC τ ) over a dosing interval (τ) and average concentration (C mean ) calculated as AUC τ /τ of TCZ after the last dose of each period. Other endpoints included PD markers (IL-6, soluble IL-6R [sIL-6R], C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]), safety (adverse events [AEs], serious AEs [SAEs]) and exploratory efficacy (rates of flare and remission). Results In 24 patients enrolled, median (range) age was 65.5 (57-90) years and the majority were female (62.5%). All patients had a history of elevated ESR and/or CRP and evidence of GCA by temporal artery biopsy and/or evidence of large vessel vasculitis at GCA diagnosis. The mean PK profile following TCZ IV 7 mg/kg Q4W in Period 1 was of a similar shape to mean PK profile following TCZ IV 6 mg/kg Q4W in Period 2, with a slightly lower exposure at ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1136/annrheumdis-2022-eular.898 |
| الاتاحة: | http://dx.doi.org/10.1136/annrheumdis-2022-eular.898 https://syndication.highwire.org/content/doi/10.1136/annrheumdis-2022-eular.898 |
| رقم الانضمام: | edsbas.A4E47028 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/annrheumdis-2022-eular.898 |
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