Association of Serum Ustekinumab Levels with Clinical Response in Psoriasis

Teresa Tsakok; Nina Wilson; Nick Dand; Floris C. Loeff; Karien Bloem; David Baudry; Michael Duckworth; Shan Pan; Angela Pushpa-Rajah; Joseph F. Standing; Annick De Vries; Ali Alsharqi; Gabrielle Becher; Ruth Murphy; Shyamal Wahie; Andrew Wright; Christopher E.M. Griffiths; Nick J. Reynolds; Jonathan Barker; Richard B. Warren; A. David Burden; Theo Rispens; Deborah Stocken; Catherine Smith

doi:10.1001/jamadermatol.2019.1783

Association of Serum Ustekinumab Levels with Clinical Response in Psoriasis

Teresa Tsakok, Nina Wilson, Nick Dand, Floris C. Loeff, Karien Bloem, David Baudry, Michael Duckworth, Shan Pan, Angela Pushpa-Rajah, Joseph F. Standing, Annick De Vries, Ali Alsharqi, Gabrielle Becher, Ruth Murphy, Shyamal Wahie, Andrew Wright, Christopher E.M. Griffiths, Nick J. Reynolds, Jonathan Barker, Richard B. WarrenA. David Burden, Theo Rispens, Deborah Stocken, Catherine Smith^*

^*Corresponding author for this work

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

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Abstract

Importance: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab. Objective: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis. Design, Setting, and Participants: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria. Exposure: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay. Main Outcomes and Measures: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less. Results: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5). Conclusions and Relevance: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome..

Original language	English
Pages (from-to)	1235-1243
Number of pages	9
Journal	JAMA dermatology
Volume	155
Issue number	11
Early online date	18 Sept 2019
DOIs	https://doi.org/10.1001/jamadermatol.2019.1783
Publication status	Published - 2019

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Tsakok, T., Wilson, N., Dand, N., Loeff, F. C., Bloem, K., Baudry, D., Duckworth, M., Pan, S., Pushpa-Rajah, A., Standing, J. F., De Vries, A., Alsharqi, A., Becher, G., Murphy, R., Wahie, S., Wright, A., Griffiths, C. E. M., Reynolds, N. J., Barker, J., ... Smith, C. (2019). Association of Serum Ustekinumab Levels with Clinical Response in Psoriasis. JAMA dermatology, 155(11), 1235-1243. https://doi.org/10.1001/jamadermatol.2019.1783

@article{4a18976a76d144c1823f809b445c8190,

title = "Association of Serum Ustekinumab Levels with Clinical Response in Psoriasis",

abstract = "Importance: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab. Objective: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis. Design, Setting, and Participants: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria. Exposure: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay. Main Outcomes and Measures: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less. Results: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5). Conclusions and Relevance: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome..",

author = "Teresa Tsakok and Nina Wilson and Nick Dand and Loeff, {Floris C.} and Karien Bloem and David Baudry and Michael Duckworth and Shan Pan and Angela Pushpa-Rajah and Standing, {Joseph F.} and {De Vries}, Annick and Ali Alsharqi and Gabrielle Becher and Ruth Murphy and Shyamal Wahie and Andrew Wright and Griffiths, {Christopher E.M.} and Reynolds, {Nick J.} and Jonathan Barker and Warren, {Richard B.} and Burden, {A. David} and Theo Rispens and Deborah Stocken and Catherine Smith",

year = "2019",

doi = "10.1001/jamadermatol.2019.1783",

language = "English",

volume = "155",

pages = "1235--1243",

journal = "JAMA dermatology",

issn = "2168-6068",

publisher = "American Medical Association",

number = "11",

}

Tsakok, T, Wilson, N, Dand, N, Loeff, FC, Bloem, K, Baudry, D , Duckworth, M, Pan, S, Pushpa-Rajah, A, Standing, JF, De Vries, A, Alsharqi, A, Becher, G, Murphy, R, Wahie, S, Wright, A, Griffiths, CEM, Reynolds, NJ, Barker, J, Warren, RB, Burden, AD, Rispens, T, Stocken, D & Smith, C 2019, 'Association of Serum Ustekinumab Levels with Clinical Response in Psoriasis', JAMA dermatology, vol. 155, no. 11, pp. 1235-1243. https://doi.org/10.1001/jamadermatol.2019.1783

TY - JOUR

T1 - Association of Serum Ustekinumab Levels with Clinical Response in Psoriasis

AU - Tsakok, Teresa

AU - Wilson, Nina

AU - Dand, Nick

AU - Loeff, Floris C.

AU - Bloem, Karien

AU - Baudry, David

AU - Duckworth, Michael

AU - Pan, Shan

AU - Pushpa-Rajah, Angela

AU - Standing, Joseph F.

AU - De Vries, Annick

AU - Alsharqi, Ali

AU - Becher, Gabrielle

AU - Murphy, Ruth

AU - Wahie, Shyamal

AU - Wright, Andrew

AU - Griffiths, Christopher E.M.

AU - Reynolds, Nick J.

AU - Barker, Jonathan

AU - Warren, Richard B.

AU - Burden, A. David

AU - Rispens, Theo

AU - Stocken, Deborah

AU - Smith, Catherine

PY - 2019

Y1 - 2019

N2 - Importance: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab. Objective: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis. Design, Setting, and Participants: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria. Exposure: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay. Main Outcomes and Measures: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less. Results: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5). Conclusions and Relevance: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome..

AB - Importance: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab. Objective: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis. Design, Setting, and Participants: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria. Exposure: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay. Main Outcomes and Measures: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less. Results: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5). Conclusions and Relevance: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome..

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U2 - 10.1001/jamadermatol.2019.1783

DO - 10.1001/jamadermatol.2019.1783

M3 - Article

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AN - SCOPUS:85072379676

SN - 2168-6068

VL - 155

SP - 1235

EP - 1243

JO - JAMA dermatology

JF - JAMA dermatology

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ER -

Association of Serum Ustekinumab Levels with Clinical Response in Psoriasis

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