Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations.
BACKGROUND
Patients with psoriasis tend to be overweight, and the efficacy of fixed-dose biologics may be compromised by high body weight.


OBJECTIVE
We sought to determine whether the optimal dose of ustekinumab is affected by weight in patients with psoriasis.


METHODS
Patients were randomized in two phase III trials (PHOENIX 1 and 2) to receive 45 mg or 90 mg of ustekinumab every 12 weeks (n = 1331) or placebo with crossover to ustekinumab at week 12 (n = 665). Efficacy and serum ustekinumab concentrations were to be evaluated by 10-kg increments of body weight at week 28 (steady-state trough level).


RESULTS
Mean baseline weight was 93.9 and 91.0 kg in PHOENIX 1 and 2, respectively. Based on the analyses by 10-kg increments, a cutoff of 100 kg was determined to best differentiate the dose response. The proportion of patients with at least 75% improvement from baseline in Psoriasis Area and Severity Index score was 74.2% for 90 mg and 54.6% for 45 mg in heavier patients (> 100 kg), but the proportion with a response of at least 75% improvement from baseline in Psoriasis Area and Severity Index score was similar between doses (80.8% vs 76.9%) in lighter patients (≤ 100 kg). Serum ustekinumab concentrations were also affected by weight, with lower serum concentrations observed in heavier patients at each dose. Safety was not affected by weight.


CONCLUSIONS
Low numbers of patients at the extremes of body weight may limit the analyses of these subgroups.


CONCLUSIONS
Results of weight-based analyses of clinical and pharmacokinetic data indicate that fixed dosing of ustekinumab based on weight is appropriate for the treatment of patients with psoriasis.
Lebwohl
Mark
M
Mount Sinai School of Medicine, New York, New York 10029, USA. Lebwohl@aol.com
Yeilding
Newman
N
Szapary
Philippe
P
Wang
Yuhua
Y
Li
Shu
S
Zhu
Yaowei
Y
Reich
Kristian
K
Langley
Richard G
RG
Papp
Kim A
KA
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D015992:Body Mass Index; D001835:Body Weight; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy*; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000069549:Ustekinumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069549:Ustekinumab