PMCCPMCCPMCC

Search tips
Search criteria 

Advanced


 
Formats
Article sections
Authors
Related links
Logo of bmjoInstructions for authorsCurrent ToCBMJ Open
 
BMJ Open. 2012; 2(5): e001524.
Published online 2012 September 21. doi:  10.1136/bmjopen-2012-001524
PMCID: PMC3467642
Copyright © 2012, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Influence of FCGR3A genotype on the therapeutic response to rituximab in rheumatoid arthritis: an observational cohort study
Alf Kastbom,1 Lars Cöster,1 Lisbeth Ärlestig,2 Aikaterini Chatzidionysiou,3,4 Ronald F van Vollenhoven,3,4 Leonid Padyukov,3 Solbritt Rantapää-Dahlqvist,2 and Saedis Saevarsdottir3
1Department of Clinical and Experimental Medicine, Linköping University/ Department of Rheumatology in Östergötland, County Council of Östergötland, Linköping, Sweden
2Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden
3Rheumatology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
4Unit for Clinical Therapy Research of Inflammatory Diseases, Department of Medicine, Karolinska Institute, Stockholm, Sweden
Correspondence to Dr Alf Kastbom; alf.kastbom/at/liu.se
Received May 23, 2012; Accepted August 23, 2012.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.
Abstract
Objectives
To determine whether a polymorphism in the Fcγ receptor type IIIA (FCGR3A-F158V), influencing immunoglobulin G binding affinity, relates to the therapeutic efficacy of rituximab in rheumatoid arthritis (RA) patients.
Design
Observational cohort study.
Setting
Three university hospital rheumatology units in Sweden.
Participants
Patients with established RA (n=177; 145 females and 32 males) who started rituximab (Mabthera) as part of routine care.
Primary outcome measures
Response to rituximab therapy in relation to FCGR3A genotype, including stratification for sex.
Results
The frequency of responders differed significantly across FCGR3A genotypes (p=0.017 in a 3×2 contingency table). Heterozygous patients showed the highest response rate at 83%, as compared with patients carrying 158FF (68%) or 158VV (56%) (p=0.028 and 0.016, respectively). Among 158VV patients, response rates differed between male and female patients (p=0.036), but not among 158FF or 158VF patients (p=0.72 and 0.46, respectively).
Conclusions
Therapeutic efficacy of rituximab in RA patients is influenced by FCGR3A genotype, with the highest response rates found among heterozygous patients. This may suggest that different rituximab mechanisms of action in RA are optimally balanced in FCGR3A-158VF patients. Similar to the previously described associations with RA susceptibility and disease course, the impact of 158VV on rituximab response may be influenced by sex.
Keywords: Rheumatology, Immunology, Therapeutics
Articles from BMJ Open are provided here courtesy of
BMJ Group