The role of the FcGRIIIa polymorphism in modifying the association between treatment and outcome in patients with rheumatoid arthritis treated with rituximab versus TNF-α antagonist therapies

Khaled Sarsour, Jeffrey Greenberg, Joseph A. Johnston, David R. Nelson, Lee A. O'Brien, Carole Oddoux, Harry Ostrer, Alex Pearlman, George Reed

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objectives There is an association between the FcGRIIIa polymorphism and the development of rheumatoid arthritis (RA). Studies in non-Hodgkin's lymphoma demonstrated a relationship between the FcGRIIIa polymorphism and response to anti-CD20 therapies. However, there are currently no published studies evaluating the relationship between this polymorphism and therapeutic response to treatment with anti-CD20 agents such as rituximab in RA. We conducted a study to identify if the FcGRIIIa polymorphism is associated with rituximab efficacy in patients with RA. Methods Subjects with RA treated with rituximab (cases, n=158) or TNF-a antagonist (controls, n=390) were recruited from the Consortium of Rheumatology Researchers of North America. The FcGRIIIa variant was genotyped for all subjects and longitudinal patient outcomes were assessed using the clinical disease activity index (CDAI). We used a linear regression random effects model to estimate CDAI scores over time with multiple time points nested within patient. Results Similar changes in CDAI were observed across the three FcGRIIIa genotypes for the rituximab treated group (VV [4.56, SD 14.5]), VF (7.44, SD 14.9) and FF (4.75, SD 10.8) (p >0.05)] and the TNF-a antagonist therapy treated group [VV (5.12, SD 14.6), VF (6.77, SD 15.9), and FF (4.36, SD 18.2) (p >0.05). Overall, there were similar changes in CDAI at 6 months for rituximab (-5.91, SD 14.1) and anti-TNFs (-5.77, SD 15.5) (p >0.05). The FcGRIIIa genotype was not significantly associated (p=0.86) with treatment response in rituximab treated RA patients compared with TNF-a antagonist therapy treated patients. Baseline CDAI and number of prior biologics were significant predictors of clinical response over time. Conclusion Our finding emphasises the idea that determinants of response to treatment are complex and may be dependent upon genetic and phenotypic interactions. Future studies should analyse the interaction between the FcGRIIIa gene, other neighbouring polymorphisms and other phenotypic and environmental factors.

Original languageEnglish (US)
Pages (from-to)189-194
Number of pages6
JournalClinical and Experimental Rheumatology
Volume31
Issue number2
StatePublished - 2013

Fingerprint

Rheumatoid Arthritis
Therapeutics
Genotype
Rheumatology
Group Psychotherapy
North America
Biological Products
Non-Hodgkin's Lymphoma
Rituximab
Linear Models
Research Personnel
Genes

Keywords

  • FcGRIIIa polymorphism
  • Genetic epidemiology
  • Response to treatment

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

The role of the FcGRIIIa polymorphism in modifying the association between treatment and outcome in patients with rheumatoid arthritis treated with rituximab versus TNF-α antagonist therapies. / Sarsour, Khaled; Greenberg, Jeffrey; Johnston, Joseph A.; Nelson, David R.; O'Brien, Lee A.; Oddoux, Carole; Ostrer, Harry; Pearlman, Alex; Reed, George.

In: Clinical and Experimental Rheumatology, Vol. 31, No. 2, 2013, p. 189-194.

Research output: Contribution to journalArticle

Sarsour, Khaled ; Greenberg, Jeffrey ; Johnston, Joseph A. ; Nelson, David R. ; O'Brien, Lee A. ; Oddoux, Carole ; Ostrer, Harry ; Pearlman, Alex ; Reed, George. / The role of the FcGRIIIa polymorphism in modifying the association between treatment and outcome in patients with rheumatoid arthritis treated with rituximab versus TNF-α antagonist therapies. In: Clinical and Experimental Rheumatology. 2013 ; Vol. 31, No. 2. pp. 189-194.
@article{37e12a3674ee4862864be5fe8c51014e,
title = "The role of the FcGRIIIa polymorphism in modifying the association between treatment and outcome in patients with rheumatoid arthritis treated with rituximab versus TNF-α antagonist therapies",
abstract = "Objectives There is an association between the FcGRIIIa polymorphism and the development of rheumatoid arthritis (RA). Studies in non-Hodgkin's lymphoma demonstrated a relationship between the FcGRIIIa polymorphism and response to anti-CD20 therapies. However, there are currently no published studies evaluating the relationship between this polymorphism and therapeutic response to treatment with anti-CD20 agents such as rituximab in RA. We conducted a study to identify if the FcGRIIIa polymorphism is associated with rituximab efficacy in patients with RA. Methods Subjects with RA treated with rituximab (cases, n=158) or TNF-a antagonist (controls, n=390) were recruited from the Consortium of Rheumatology Researchers of North America. The FcGRIIIa variant was genotyped for all subjects and longitudinal patient outcomes were assessed using the clinical disease activity index (CDAI). We used a linear regression random effects model to estimate CDAI scores over time with multiple time points nested within patient. Results Similar changes in CDAI were observed across the three FcGRIIIa genotypes for the rituximab treated group (VV [4.56, SD 14.5]), VF (7.44, SD 14.9) and FF (4.75, SD 10.8) (p >0.05)] and the TNF-a antagonist therapy treated group [VV (5.12, SD 14.6), VF (6.77, SD 15.9), and FF (4.36, SD 18.2) (p >0.05). Overall, there were similar changes in CDAI at 6 months for rituximab (-5.91, SD 14.1) and anti-TNFs (-5.77, SD 15.5) (p >0.05). The FcGRIIIa genotype was not significantly associated (p=0.86) with treatment response in rituximab treated RA patients compared with TNF-a antagonist therapy treated patients. Baseline CDAI and number of prior biologics were significant predictors of clinical response over time. Conclusion Our finding emphasises the idea that determinants of response to treatment are complex and may be dependent upon genetic and phenotypic interactions. Future studies should analyse the interaction between the FcGRIIIa gene, other neighbouring polymorphisms and other phenotypic and environmental factors.",
keywords = "FcGRIIIa polymorphism, Genetic epidemiology, Response to treatment",
author = "Khaled Sarsour and Jeffrey Greenberg and Johnston, {Joseph A.} and Nelson, {David R.} and O'Brien, {Lee A.} and Carole Oddoux and Harry Ostrer and Alex Pearlman and George Reed",
year = "2013",
language = "English (US)",
volume = "31",
pages = "189--194",
journal = "Clinical and Experimental Rheumatology",
issn = "0392-856X",
publisher = "Clinical and Experimental Rheumatology S.A.S.",
number = "2",

}

TY - JOUR

T1 - The role of the FcGRIIIa polymorphism in modifying the association between treatment and outcome in patients with rheumatoid arthritis treated with rituximab versus TNF-α antagonist therapies

AU - Sarsour, Khaled

AU - Greenberg, Jeffrey

AU - Johnston, Joseph A.

AU - Nelson, David R.

AU - O'Brien, Lee A.

AU - Oddoux, Carole

AU - Ostrer, Harry

AU - Pearlman, Alex

AU - Reed, George

PY - 2013

Y1 - 2013

N2 - Objectives There is an association between the FcGRIIIa polymorphism and the development of rheumatoid arthritis (RA). Studies in non-Hodgkin's lymphoma demonstrated a relationship between the FcGRIIIa polymorphism and response to anti-CD20 therapies. However, there are currently no published studies evaluating the relationship between this polymorphism and therapeutic response to treatment with anti-CD20 agents such as rituximab in RA. We conducted a study to identify if the FcGRIIIa polymorphism is associated with rituximab efficacy in patients with RA. Methods Subjects with RA treated with rituximab (cases, n=158) or TNF-a antagonist (controls, n=390) were recruited from the Consortium of Rheumatology Researchers of North America. The FcGRIIIa variant was genotyped for all subjects and longitudinal patient outcomes were assessed using the clinical disease activity index (CDAI). We used a linear regression random effects model to estimate CDAI scores over time with multiple time points nested within patient. Results Similar changes in CDAI were observed across the three FcGRIIIa genotypes for the rituximab treated group (VV [4.56, SD 14.5]), VF (7.44, SD 14.9) and FF (4.75, SD 10.8) (p >0.05)] and the TNF-a antagonist therapy treated group [VV (5.12, SD 14.6), VF (6.77, SD 15.9), and FF (4.36, SD 18.2) (p >0.05). Overall, there were similar changes in CDAI at 6 months for rituximab (-5.91, SD 14.1) and anti-TNFs (-5.77, SD 15.5) (p >0.05). The FcGRIIIa genotype was not significantly associated (p=0.86) with treatment response in rituximab treated RA patients compared with TNF-a antagonist therapy treated patients. Baseline CDAI and number of prior biologics were significant predictors of clinical response over time. Conclusion Our finding emphasises the idea that determinants of response to treatment are complex and may be dependent upon genetic and phenotypic interactions. Future studies should analyse the interaction between the FcGRIIIa gene, other neighbouring polymorphisms and other phenotypic and environmental factors.

AB - Objectives There is an association between the FcGRIIIa polymorphism and the development of rheumatoid arthritis (RA). Studies in non-Hodgkin's lymphoma demonstrated a relationship between the FcGRIIIa polymorphism and response to anti-CD20 therapies. However, there are currently no published studies evaluating the relationship between this polymorphism and therapeutic response to treatment with anti-CD20 agents such as rituximab in RA. We conducted a study to identify if the FcGRIIIa polymorphism is associated with rituximab efficacy in patients with RA. Methods Subjects with RA treated with rituximab (cases, n=158) or TNF-a antagonist (controls, n=390) were recruited from the Consortium of Rheumatology Researchers of North America. The FcGRIIIa variant was genotyped for all subjects and longitudinal patient outcomes were assessed using the clinical disease activity index (CDAI). We used a linear regression random effects model to estimate CDAI scores over time with multiple time points nested within patient. Results Similar changes in CDAI were observed across the three FcGRIIIa genotypes for the rituximab treated group (VV [4.56, SD 14.5]), VF (7.44, SD 14.9) and FF (4.75, SD 10.8) (p >0.05)] and the TNF-a antagonist therapy treated group [VV (5.12, SD 14.6), VF (6.77, SD 15.9), and FF (4.36, SD 18.2) (p >0.05). Overall, there were similar changes in CDAI at 6 months for rituximab (-5.91, SD 14.1) and anti-TNFs (-5.77, SD 15.5) (p >0.05). The FcGRIIIa genotype was not significantly associated (p=0.86) with treatment response in rituximab treated RA patients compared with TNF-a antagonist therapy treated patients. Baseline CDAI and number of prior biologics were significant predictors of clinical response over time. Conclusion Our finding emphasises the idea that determinants of response to treatment are complex and may be dependent upon genetic and phenotypic interactions. Future studies should analyse the interaction between the FcGRIIIa gene, other neighbouring polymorphisms and other phenotypic and environmental factors.

KW - FcGRIIIa polymorphism

KW - Genetic epidemiology

KW - Response to treatment

UR - http://www.scopus.com/inward/record.url?scp=84875776328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875776328&partnerID=8YFLogxK

M3 - Article

C2 - 23294992

AN - SCOPUS:84875776328

VL - 31

SP - 189

EP - 194

JO - Clinical and Experimental Rheumatology

JF - Clinical and Experimental Rheumatology

SN - 0392-856X

IS - 2

ER -