Session Type: Abstract Submissions (ACR)
Background/Purpose: The current shift to earlier treatment of Rheumatoid Arthritis (RA) has a major unmet need in the availability of biomarkers to identify patients requiring more intensive treatment, even in undifferentiated disease stages. Vasoactive intestinal peptide (VIP) has demonstrated physiological anti-inflammatory and immunoregulatory roles both in murine arthritis models and in “in vitro” studies with human synoviocytes and lymphocytes by decreasing the expression of proinflammatory molecules and favouring Th2 responses. In addition, low levels of VIP expression in the synovial fluid of severe forms of osteoarthritis has been described.
The aim of this work is to analyze the potential value of studying VIP serum levels (VIPs) as a prognostic biomarker in RA by longitudinal assessment of its levels in patients with early arthritis (EA).
Methods: We studied 91 patients from our prospective EA registry, in which we collect by protocol sociodemographic, clinical, laboratory, and therapeutic information. 73% were female, with age at disease onset 54 years [45-66] (median [p25-p75] ), duration of disease at entry 5.4 [3.2-8.4] months and follow-up 2 to 5 years. 76% of patients met 1987 ACR classification criteria for RA after two years of follow up. VIPs were measured by ELISA (Phoenix Pharmaceutical, Karlshure, Germany) in the patients sera collected from 353 visits (3.8 visits per patient), and in 100 healthy controls. Low VIPs were considered if below the 25th percentile of the normal population. We created the variable treatment intensity (IT) as the sum of the number of days on treatment with each disease modifying anti-rheumatic drugs, including biologics. To determine the effect of independent variables on VIPs, we performed a longitudinal multivariate analysis, nested by patient and visit, through the command xtgee of Stata 12 for Windows (StataCorp LP, College Station, TX, USA).
Results: We could not detect significant differences in the VIPs between patients and controls either at their first visit (409 pg / ml [359-469] versus 403 [371-441] respectively, p = 0.915) or over the two year follow-up. Nevertheless, substantial heterogeneity in these levels was observed. Multivariate analysis aimed to deepen this VIPs heterogeneity showed differences by gender (being female beta coefficient [coef. Beta]: 0.25 ± 0.09, P = 0.007) and age of disease onset (coef. beta per year 0.003 ± 0.007, P = 0.006). In terms of disease-related variables, VIPs were lower in subjects with greater disease activity measured by DAS28 (coef. beta: -0.043 ± 0.019, P = 0.026). In addition, patients with lower VIPs at the first visit had higher disease activity at the end of follow-up (3.47 [2.83-4.37] versus 3.03 [2.16-3.77], p = 0.14) and received more intense treatment according to the variable IT (1352 [1092-1754] vs 1119 [870-1473], p = 0.22).
Conclusion: Our data suggest that VIPs may be a prognostic biomarker in RA since baseline levels are lower in patients who show a worse clinical course and increased requirements for treatment in the first two years of disease monitoring.
A. M. Ortiz,
R. P. Gomariz,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/vasoactive-intestinal-peptide-serum-levels-as-a-marker-of-prognosis-in-rheumatoid-arthritis/