Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol

Longitudinal Data from a 7-Year Study in Crohn's Disease

William J. Sandborn, Douglas C. Wolf, Gordana Kosutic, Gerry Parker, Stefan Schreiber, Scott D. Lee, Bincy Abraham, Anita Afzali, Razvan Arsenescu, Alexandra Gutierrez, Marshall Spearman, Jason Coarse, Brian G. Feagan

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohn's disease. Methods: PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP-ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables. Results: Of the CZP-ADAb-positive patients, 40 (22.6%) had transient CZP-ADAbs and 94 (77.4%) had persistent CZP-ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group. Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups. Conclusions: This analysis demonstrates that persistent CZP-ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524.

Original languageEnglish (US)
Pages (from-to)1047-1056
Number of pages10
JournalInflammatory Bowel Diseases
Volume23
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

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Crohn Disease
Anti-Idiotypic Antibodies
Pharmaceutical Preparations
Leukocyte L1 Antigen Complex
C-Reactive Protein
Certolizumab Pegol
Biological Products
Necrosis

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Sandborn, William J. ; Wolf, Douglas C. ; Kosutic, Gordana ; Parker, Gerry ; Schreiber, Stefan ; Lee, Scott D. ; Abraham, Bincy ; Afzali, Anita ; Arsenescu, Razvan ; Gutierrez, Alexandra ; Spearman, Marshall ; Coarse, Jason ; Feagan, Brian G. / Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol : Longitudinal Data from a 7-Year Study in Crohn's Disease. In: Inflammatory Bowel Diseases. 2017 ; Vol. 23, No. 7. pp. 1047-1056.
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title = "Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol: Longitudinal Data from a 7-Year Study in Crohn's Disease",
abstract = "Background: Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohn's disease. Methods: PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP-ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables. Results: Of the CZP-ADAb-positive patients, 40 (22.6{\%}) had transient CZP-ADAbs and 94 (77.4{\%}) had persistent CZP-ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group. Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups. Conclusions: This analysis demonstrates that persistent CZP-ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524.",
author = "Sandborn, {William J.} and Wolf, {Douglas C.} and Gordana Kosutic and Gerry Parker and Stefan Schreiber and Lee, {Scott D.} and Bincy Abraham and Anita Afzali and Razvan Arsenescu and Alexandra Gutierrez and Marshall Spearman and Jason Coarse and Feagan, {Brian G.}",
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Sandborn, WJ, Wolf, DC, Kosutic, G, Parker, G, Schreiber, S, Lee, SD, Abraham, B, Afzali, A, Arsenescu, R, Gutierrez, A, Spearman, M, Coarse, J & Feagan, BG 2017, 'Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol: Longitudinal Data from a 7-Year Study in Crohn's Disease', Inflammatory Bowel Diseases, vol. 23, no. 7, pp. 1047-1056. https://doi.org/10.1097/MIB.0000000000001100

Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol : Longitudinal Data from a 7-Year Study in Crohn's Disease. / Sandborn, William J.; Wolf, Douglas C.; Kosutic, Gordana; Parker, Gerry; Schreiber, Stefan; Lee, Scott D.; Abraham, Bincy; Afzali, Anita; Arsenescu, Razvan; Gutierrez, Alexandra; Spearman, Marshall; Coarse, Jason; Feagan, Brian G.

In: Inflammatory Bowel Diseases, Vol. 23, No. 7, 01.07.2017, p. 1047-1056.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol

T2 - Longitudinal Data from a 7-Year Study in Crohn's Disease

AU - Sandborn, William J.

AU - Wolf, Douglas C.

AU - Kosutic, Gordana

AU - Parker, Gerry

AU - Schreiber, Stefan

AU - Lee, Scott D.

AU - Abraham, Bincy

AU - Afzali, Anita

AU - Arsenescu, Razvan

AU - Gutierrez, Alexandra

AU - Spearman, Marshall

AU - Coarse, Jason

AU - Feagan, Brian G.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Background: Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohn's disease. Methods: PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP-ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables. Results: Of the CZP-ADAb-positive patients, 40 (22.6%) had transient CZP-ADAbs and 94 (77.4%) had persistent CZP-ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group. Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups. Conclusions: This analysis demonstrates that persistent CZP-ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524.

AB - Background: Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohn's disease. Methods: PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP-ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables. Results: Of the CZP-ADAb-positive patients, 40 (22.6%) had transient CZP-ADAbs and 94 (77.4%) had persistent CZP-ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group. Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups. Conclusions: This analysis demonstrates that persistent CZP-ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524.

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U2 - 10.1097/MIB.0000000000001100

DO - 10.1097/MIB.0000000000001100

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EP - 1056

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

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