Evaluating Dosage Optimality for Tofacitinib, an Oral Janus Kinase Inhibitor, in Plaque Psoriasis, and the Influence of Body Weight.
Tofacitinib is an oral Janus kinase inhibitor. An integrated analysis was conducted to evaluate dosage optimality for tofacitinib in patients with moderate-to-severe plaque psoriasis and the impact of body weight on optimality in this patient population. Data were pooled from one phase IIb trial (2, 5, and 15 mg twice daily (b.i.d.)) and four phase III trials (5 and 10 mg b.i.d.). A longitudinal exposure-response model for Psoriasis Area and Severity Index (PASI) improvement (percent change from baseline) was established. Body weight influenced potency; heavier subjects require higher doses to achieve comparable benefit to lighter subjects. Disease severity, sex, and prior biologic usage were also predictive of response. The 10 and 5 mg doses were predicted to achieve 81% and 65%, respectively, of the maximum effect based on a 75% improvement in PASI. The greater efficacy of 10 mg over 5 mg was clinically meaningful.
Ann Arbor Pharmacometrics Group (A2PG), Inc., Ann Arbor, Michigan, USA.
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Hutmacher
Probity Medical Research and K Papp Clinical Research Inc., Waterloo, Ontario, Canada.
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Papp
Pfizer Inc., Groton, Connecticut, USA.
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Krishnaswami
Pfizer Inc., Groton, Connecticut, USA.
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Ito
Pfizer Inc., Groton, Connecticut, USA.
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Tan
Pfizer Inc., Groton, Connecticut, USA.
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Wolk
Pfizer Inc., Groton, Connecticut, USA.
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Valdez
Pfizer Inc., Groton, Connecticut, USA.
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Mebus
Pfizer Inc., Groton, Connecticut, USA.
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Rottinghaus
Pfizer Inc., Groton, Connecticut, USA.
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Gupta
D000284:Administration, Oral; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000075242:Janus Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010880:Piperidines / Q000008:administration & dosage* / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
D000075242:Janus Kinase Inhibitors; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib