Ravulizumab pharmacokinetics and pharmacodynamics in patients with generalized myasthenia gravis

被引:26
作者
Vu, Tuan [1 ]
Ortiz, Stephan [2 ]
Katsuno, Masahisa [3 ]
Annane, Djillali [4 ]
Mantegazza, Renato [5 ]
Beasley, Kathleen N. [2 ]
Aguzzi, Rasha [2 ]
Howard, James F. [6 ]
机构
[1] Univ S Florida, Morsani Coll Med, Tampa, FL USA
[2] Alexion, AstraZeneca Rare Dis, Boston, MA 02210 USA
[3] Nagoya Univ, Grad Sch Med, Nagoya, Japan
[4] Univ Versailles, Hop Raymond Poincare, Garches, France
[5] Fdn IRCCS Ist Neurol Carlo Besta, Milan, Italy
[6] Univ N Carolina, Chapel Hill, NC USA
关键词
Complement; Generalized myasthenia gravis; Pharmacodynamics; Pharmacokinetics; Ravulizumab; RECEPTOR DENSITY; IN-VIVO; COMPLEMENT;
D O I
10.1007/s00415-023-11617-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
IntroductionThe terminal complement C5 inhibitor ravulizumab has a long elimination half-life, allowing maintenance dosing every 8 weeks. In the 26-week, double-blind, randomized, placebo-controlled period (RCP) of the CHAMPION MG study, ravulizumab provided rapid and sustained efficacy and was well tolerated in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG). This analysis evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and potential immunogenicity of ravulizumab in adults with AChR Ab+ gMG.MethodsData were analyzed from 86 patients who received ravulizumab in the CHAMPION MG RCP. Ravulizumab dosing was weight-based: initial loading dose of 2400/2700/3000 mg on Day 1 and maintenance doses of 3000/3300/3600 mg on Day 15 and then every 8 weeks. PK parameters were estimated from serum ravulizumab concentrations determined pre- and post-dose; PD effects of ravulizumab on serum free C5 concentrations were measured; and immunogenicity was assessed using anti-drug antibody and neutralizing-antibody assays.ResultsTarget serum ravulizumab concentrations (> 175 mu g/mL) were achieved immediately after the first ravulizumab dose (within 30 min of infusion completion) and maintained throughout the 26-week treatment period irrespective of patient body weight. Following the final maintenance dose, mean C-max was 1548 mu g/mL and C-trough 587 mu g/mL; no meaningful differences were noted among body-weight categories. Inhibition of serum free C5 was immediate, complete (< 0.5 mu g/mL), and sustained throughout treatment in all patients. No treatment-emergent anti-drug antibodies were observed.ConclusionsPK/PD evidence supports the use of ravulizumab every 8 weeks for immediate, complete, and sustained inhibition of terminal complement C5 in adults with AChR Ab+ gMG.
引用
收藏
页码:3129 / 3137
页数:9
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