Background: It has been reported that patients with recent-onset arthritis homozygous for the minor allele (TT) of the single nucleotide polymorphism (SNP) rs7574865 in STAT4 have worse disease activity in their evolution.

Objectives: Analyze if patients with ARC of TT genotype of this SNP have a higher number of comorbidities and complications associated with rheumatoid arthritis than GG/GT patients.

Methods: We retrospectively collected presence and date of diagnosis of comorbidities (HTA, DM, DL, ICC, ischemic heart disease, EPOC, depression, gastroduodenal ulcer, osteoporosis or cancer) and complications of RA (atloaxoid dislocation, interstitial pneumopathy, ocular involvement, Sjögren’s syndrome, serositis, peripheral vasculopathy, Felty’s syndrome or amyloidosis) by reviewing the hospital and primary care medical records of the patients included in PEARL study between September 2001 and September 2022, so that the minimum follow-up was 2 years. The median follow-up for the collection of comorbidities and complications was 6 years [p25-p75= 4-9]. In PEARL, clinical, sociodemographic, analytical and therapeutic data were collected in a protocolized manner at baseline, 6, 12 and 24 months of follow-up. All the information was compiled in an anonymized database for analysis, using Fisher’s exact test for categorical variables and Mann Whitney U for continuous variables.

Results: 580 patients (79% women) were included in the study, 71% comply with ACR/EULAR 2010 criteria for rheumatoid arthritis (RA) and 29% were considered undifferentiated arthritis (UA). There were no significant differences between genotypes in terms of RF or ACPA positivity or final diagnosis. There was a non-significant trend for patients with the T allele to be younger (GG 56 years [47-67; p25-p75], GT 54 years [41-67] and TT 51 years [43-64]; p=0’069). Baseline activity was similar in all three genotypes, but at 2-year follow-up TT patients maintained significantly higher levels of activity according to the HUPI index (p=0.02). 15% percent of TT patients had at least one systemic complication compared to 6.5% of GT/GG patients (p=0.012). Among the complications studied, significant differences were only found in ocular involvement (9.52% of TT patients vs. 0.71% of GT/GG patients; p=0.002). In the overall study by comorbidities no significant differences were found between rs7574865 genotypes. In the analysis by individual comorbidities, 29% of TT patients were diagnosed with depression versus 14% in GT/GG (p=0.021). There was also a non-significant trend to higher frequency of EPOC in TT patients (7% vs 3%; p=0’127) and to having suffered any type of cancer (12% vs 6%; p=0’101).

Conclusion: Our study validates previously results of worse arthritis control in TT patients of rs7574865 in STAT4, which could explain why this subpopulation presents more arthritis-associated complications. The higher frequency of depression should be validated in other populations to confirm its relationship.

REFERENCES: [1] Lamana A, et al. The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis. PLoS One. 2012;7(8):e43661.

Acknowledgements: This study was funded with grants: RD21/0002/0027, PI21/00526 y PI24/00138 from Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) and co-funded by European regional development fund (ERDF) “A way to make Europe” and the project SPIDeRR funded from the Horizon Europe programme under grant agreement 101080711.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.