Background/Purpose: A strong genetic association between HLA-DRB1 alleles containing the shared epitope (SE) and RA has been described.¹ The SE has been associated with ACPA positivity,² earlier onset of RA,³ harder-to-treat disease² and poor prognosis.⁴ The purpose of this analysis was to assess whether ACPA and SE status are associated with risk of hospitalization in RA.

Methods: This was a retrospective analysis of patients (pts) enrolled in the Brigham and Women’s Rheumatoid Arthritis Sequential Study (NCT01793103; BRASS) registry between March 2003 and June 2019. Pts with known ACPA and SE status were included. HLA-DRB1 SE status (1 or 2 alleles [+], 0 alleles [–]) was determined by allele-specific polymerase chain reaction and DNA sequencing for most pts and by genome-wide association study-based imputation for the others. Pts were stratified by ACPA and SE status. Index date was the date of the baseline visit. Baseline demographics and disease characteristics, hospitalization rates (yes/no) and causes of hospitalization over 6 and 24 months were reported descriptively. Associations between SE status and hospitalization were examined using multivariable adjusted logistic regression models.

Results: Of 961 pts with known ACPA and SE status included in the analysis, 641 were ACPA+ and 620 were SE+ (466 [48%] were both ACPA+ and SE+). In ACPA+ pts, most baseline characteristics were similar between those who were SE+ and SE– (Table 1); SE+ vs SE– pts were more likely to receive conventional synthetic or biologic DMARDs. Among ACPA– pts, SE+ vs  SE– pts had longer RA duration and were more likely to be RF+. Among ACPA+ pts 6 months after index date, the rate of hospitalization in SE+ pts was twice that for SE– pts (12.3% vs 5.3%; p=0.0156); joint replacement and cardiovascular (CV) conditions combined were more common causes of hospitalization in SE+ pts (50%) than SE– pts (25%; Table 2). Similarly, among ACPA+ pts 24 months after index date, the rate of hospitalization remained significantly higher for SE+ vs SE– pts (29% vs 21%; p=0.0487), with joint replacement and CV conditions combined being more common causes of hospitalization (SE+, 42% vs SE–, 26%; Table 2). No notable differences were seen in ACPA– pts. Among ACPA+ pts, the adjusted risk of hospitalization was 4.84-fold higher in SE+ vs SE– pts at 6 months (p=0.0036) and 1.56-fold higher at 24 months (p=0.0793; Figure 1). Overall, joint replacement and CV conditions combined accounted for 46.0% and 24.0% of hospitalizations at 6 months in SE+ vs SE– pts and 39.9% and 29.2% of hospitalizations at 24 months, respectively.

Conclusion: In ACPA+ pts with established RA, being SE+ increased the risk of hospitalization over 6 months approximately 5-fold. The majority of the increased risk in hospitalization was accounted for by joint replacement and CV conditions, indicating the more rapidly progressive disease and greater co-morbidity burden associated with SE+ in this pt population.

References

1. Gregersen PK, et al. Arthritis Rheum 1987;30:1205–1213.
2. Zhuo J, et al. Presented at the EULAR 2020. Poster SAT0061.
3. Wu H, et al. Arthritis Rheum 2004;50:3093–3103.
4. Alemao E, et al. Arthritis Rheumatol 2018;70(suppl 10):abstract 71.

Medical writing: Andrea Plant (Caudex).

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-risk-of-hospitalization-in-patients-with-ra-who-are-acpa-positive-and-shared-epitope-positive/