Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Analysis of Genetic Influence of HLA-DRB1, IL4R, and FcRIIb on Radiographic Responses to Methotrexate Monotherapy or Adalimumab Plus Methotrexate Through 26 Weeks in Patients with Early Rheumatoid Arthritis.
Skapenko1, Alla, Smolen2, Josef, Kavanaugh3, Arthur, Santra4, Sourav, Kupper5, Hartmut, Peterson4, Theresa, Schulze-Koops1, Hendrik
University of Munich, Munich, Germany
Medical University of Vienna and Hietzing Hospital, Vienna, Austria
University of California San Diego, La Jolla, CA
Abbott, Abbott Park, IL
Abbott, Ludwigshafen, Germany
Background/Purpose:
Genetic factors may influence the susceptibility, severity, and radiographic progression of rheumatoid arthritis (RA). Specifically, the IL4R (A®G [I50V]) single nucleotide polymorphism (SNP) has been associated with early joint erosion,1 and the FcgRIIb (T®C [I232T]) SNP is a candidate factor for rapid radiologic joint damage.2 Their association with radiographic progression during treatment with anti-TNF agents is unclear. The purpose of this study was to examine radiographic progression through 26 weeks in pts treated with adalimumab plus methotrexate (ADA+MTX) or placebo (PBO)+MTX according to 3 candidate genetic markers: IL4R I50V SNP, HLA-DRB1 shared epitope (SE), and FcgRIIb I232T SNP.
Methods:
MTX-naïve pts >=18 years old with RA <1 year and active disease (DAS28[CRP] >3.2, ESR >=28 mm/h or CRP >=1.5 mg/dL), and either >1 erosion, RF+, or anti-CCP+ were randomized to ADA+MTX (n=515) or PBO+MTX (n=517) for 26 wks. This analysis presents radiographic outcomes, including the percentage (%) of pts with progression in modified Total Sharp Score (DmTSS >0.5) and rapid radiographic progression (RRP, DmTSS >1.5) from baseline (BL) to 26 wks by IL4R I50V SNPs (AA, AG, or GG), HLA-DRB SE copy number (0x, 1x, 2x), and FcgRIIb I232T SNPs (TT, TC, CC). Multiple imputation analyses were used to assess radiographic data.
Results:
Genetic data were available for 451 PBO+MTX and 443 ADA+MTX pts. The number (%) of pts with available radiographic data at wk 26 by genotype is lower than that of those genetically analyzed (Figure). The distribution of alleles was similar between treatment groups for IL4R and SE; however, the FcgRIIb SNPs were unequally distributed: the PBO+MTX group had more TC and fewer TT pts. BL demographics were similar across alleles, except a higher proportion of anti-CCP+ pts were noted with increasing SE copies. There were no consistent patterns of influence of IL4R SNP, SE copy number, or FcgRIIb SNP on the % of pts with DmTSS >0.5 (Figure) or RRP at wk 26.
Conclusion:
Regardless of genetic background, a higher % of pts in the PBO+MTX group exhibited radiographic progression compared with ADA+MTX. Based on previous studies,1–2 it is somewhat unexpected that neither the IL4R nor the FcgRIIb SNP influenced radiographic progression. Possible reasons for this difference may be that the study population was pre-selected for pts with risk for aggressive erosive disease, the analysis was performed after a shorter duration of treatment, and the overall increase in mTSS was moderate. Further exploration is warranted to determine any potential interactions in response to anti-TNF agents.
1.Prots, I, et al. Arthritis Rheum 2006;54:1491–1500.
2.Radstake, TR, et al. Arthritis Rheum 2006;54:3828–37.
To cite this abstract, please use the following information:
Skapenko, Alla, Smolen, Josef, Kavanaugh, Arthur, Santra, Sourav, Kupper, Hartmut, Peterson, Theresa, et al; Analysis of Genetic Influence of HLA-DRB1, IL4R, and FcRIIb on Radiographic Responses to Methotrexate Monotherapy or Adalimumab Plus Methotrexate Through 26 Weeks in Patients with Early Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :154
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