Exploring pancreatic cancer risk in rheumatoid arthritis and role of rheumatoid factor test: A retrospective cohort study using NIH All of Us database.

Abstract

e16496 Background: Pancreatic cancer (PC) has rising mortality, emphasizing the need for improved risk stratification. Rheumatoid arthritis (RA) is a chronic autoimmune disease with a known risk of hematologic malignancies and pancreatitis, but its association with PC is less well defined. Methods: A retrospective cohort study was done using NIH All of Us program. RA cases were identified using ICD codes, and the index date was the first documented RA diagnosis. Each case of RA was matched 1:1 to non-RA control on birth year, sex at birth and calendar year of index date. The primary outcome was incidence of PC occurring after RA index date. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Lag analyses at 2 and 5 years after RA diagnosis were conducted to mitigate potential reverse causation and surveillance bias. In a secondary analysis, we assessed the relevance of Rheumatoid Factor (RF) testing among PC patients. Patients with PC diagnosis with ICD codes were identified and RF test was extracted. To reduce confounding from malignancy-associated immune activation, only RF testing performed at least one year prior to PC diagnosis was included. Multivariable logistic regression was performed adjusting for demographic covariates. Survival outcomes were analyzed using adjusted Cox proportional hazards for regression. Results: A total of 11,375 patients with RA were matched to 11,375 non-RA controls with comparable follow-up (median 2,350 vs 2,141 days). During follow-up,195 patients with RA had PC incidence compared with 3 among the control group. RA diagnosis was strongly associated with PC risk (HR of 55.8 , 95% CI 17.8-174.5 , p < 0.001). Further lag analysis was done in 2 years and 5 years which were consistent with high HR (2-year lag: HR 30.2, 95% CI 9.6–95.4; 5-year lag: HR 17.0, 95% CI 5.3–54.6;both p< 0.001).Secondary analysis identified 1203 PC patients and 140 of those patients had RF level checked. Among the 140 PC patients with RF testing, 114 (81.4%) were RF-positive. and 26 (18.6%) were RF-negative. The overall cohort had a median age of 73.5 years (IQR 65.5–79.8) and a mean age of 73.2 ± 10.3 years. In multivariable logistic regression, age was the only independent factor associated with RF positivity, with a 75% increase in odds per 10-year age increase (OR 1.75; p = 0.011). Female sex was not independently associated with RF positivity (OR 1.27; p = 0.61). In adjusted Cox regression analysis, RF positivity was not associated with overall survival (HR 1.15, 95% CI 0.42–3.15; p = 0.79). Conclusions: This study showed that RA is an independent risk factor for PC, with risk persisting after lag analyses. However, antecedent RF testing and positivity may not have significant utility for screening or prognosis of PC. Further longitudinal studies are required to better understand the causal relationship and screening utility.