Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-α monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris

Alice B. Gottlieb; Salman Masud; Rallapalli Ramamurthi; Ahsan Abdulghani; Pat Romano; Umesh Chaudhari; Lisa T. Dooley; Adedigbo A. Fasanmade; Carrie L. Wagner

doi:10.1067/mjd.2003.10

Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-α monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris

Alice B. Gottlieb, Salman Masud, Rallapalli Ramamurthi, Ahsan Abdulghani, Pat Romano, Umesh Chaudhari, Lisa T. Dooley, Adedigbo A. Fasanmade, Carrie L. Wagner

Research output: Contribution to journal › Article › peer-review

157 Scopus citations

Abstract

Objective: Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial. Methods: Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6. Immunohistochemical analysis of lesional (weeks 0, 2, 10) and nonlesional (week 0) biopsies was conducted. Median infliximab half-life and peak serum concentrations over time were calculated. Results: Infliximab immunotherapy resulted in rapid and dramatic decreases in epidemial inflammation and normalization of keratinocyte differentiation in psoriatic plaques; these changes preceded maximal clinical response. Infliximab concentrations were maintained above the detection limit (0.1 mg/mL) in the majority of patients through week 14. Conclusion: The clinical and immunohistologic data demonstrate a pivotal role for tumor necrosis factor-α in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-α.

Original language	English
Pages (from-to)	68-75
Number of pages	8
Journal	Journal of the American Academy of Dermatology
Volume	48
Issue number	1
DOIs	https://doi.org/10.1067/mjd.2003.10
State	Published - Jan 2003
Externally published	Yes

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Gottlieb, A. B., Masud, S., Ramamurthi, R., Abdulghani, A., Romano, P., Chaudhari, U., Dooley, L. T., Fasanmade, A. A., & Wagner, C. L. (2003). Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-α monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris. Journal of the American Academy of Dermatology, 48(1), 68-75. https://doi.org/10.1067/mjd.2003.10

@article{6a3f65aba61b4907a215d56afdd05650,

title = "Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-α monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris",

abstract = "Objective: Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial. Methods: Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6. Immunohistochemical analysis of lesional (weeks 0, 2, 10) and nonlesional (week 0) biopsies was conducted. Median infliximab half-life and peak serum concentrations over time were calculated. Results: Infliximab immunotherapy resulted in rapid and dramatic decreases in epidemial inflammation and normalization of keratinocyte differentiation in psoriatic plaques; these changes preceded maximal clinical response. Infliximab concentrations were maintained above the detection limit (0.1 mg/mL) in the majority of patients through week 14. Conclusion: The clinical and immunohistologic data demonstrate a pivotal role for tumor necrosis factor-α in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-α.",

author = "Gottlieb, {Alice B.} and Salman Masud and Rallapalli Ramamurthi and Ahsan Abdulghani and Pat Romano and Umesh Chaudhari and Dooley, {Lisa T.} and Fasanmade, {Adedigbo A.} and Wagner, {Carrie L.}",

note = "Funding Information: Funding sources: Supported in part by Centocor Inc, a COSAT grant from the Johnson and Johnson Focused Giving Program, general support of the Clinical Research Center by Merck Inc, and a grant from the Dr David Ju Foundation. ",

year = "2003",

month = jan,

doi = "10.1067/mjd.2003.10",

language = "English",

volume = "48",

pages = "68--75",

journal = "Journal of the American Academy of Dermatology",

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Gottlieb, AB, Masud, S, Ramamurthi, R, Abdulghani, A, Romano, P, Chaudhari, U, Dooley, LT, Fasanmade, AA & Wagner, CL 2003, 'Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-α monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris', Journal of the American Academy of Dermatology, vol. 48, no. 1, pp. 68-75. https://doi.org/10.1067/mjd.2003.10

Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-α monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris. / Gottlieb, Alice B.; Masud, Salman; Ramamurthi, Rallapalli et al.
In: Journal of the American Academy of Dermatology, Vol. 48, No. 1, 01.2003, p. 68-75.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-α monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris

AU - Gottlieb, Alice B.

AU - Masud, Salman

AU - Ramamurthi, Rallapalli

AU - Abdulghani, Ahsan

AU - Romano, Pat

AU - Chaudhari, Umesh

AU - Dooley, Lisa T.

AU - Fasanmade, Adedigbo A.

AU - Wagner, Carrie L.

N1 - Funding Information: Funding sources: Supported in part by Centocor Inc, a COSAT grant from the Johnson and Johnson Focused Giving Program, general support of the Clinical Research Center by Merck Inc, and a grant from the Dr David Ju Foundation.

PY - 2003/1

Y1 - 2003/1

N2 - Objective: Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial. Methods: Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6. Immunohistochemical analysis of lesional (weeks 0, 2, 10) and nonlesional (week 0) biopsies was conducted. Median infliximab half-life and peak serum concentrations over time were calculated. Results: Infliximab immunotherapy resulted in rapid and dramatic decreases in epidemial inflammation and normalization of keratinocyte differentiation in psoriatic plaques; these changes preceded maximal clinical response. Infliximab concentrations were maintained above the detection limit (0.1 mg/mL) in the majority of patients through week 14. Conclusion: The clinical and immunohistologic data demonstrate a pivotal role for tumor necrosis factor-α in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-α.

AB - Objective: Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial. Methods: Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6. Immunohistochemical analysis of lesional (weeks 0, 2, 10) and nonlesional (week 0) biopsies was conducted. Median infliximab half-life and peak serum concentrations over time were calculated. Results: Infliximab immunotherapy resulted in rapid and dramatic decreases in epidemial inflammation and normalization of keratinocyte differentiation in psoriatic plaques; these changes preceded maximal clinical response. Infliximab concentrations were maintained above the detection limit (0.1 mg/mL) in the majority of patients through week 14. Conclusion: The clinical and immunohistologic data demonstrate a pivotal role for tumor necrosis factor-α in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-α.

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SN - 0190-9622

VL - 48

SP - 68

EP - 75

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

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ER -

Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-α monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris

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