The Relationship between Serum IL-37 and Disease Activity in Patients with Rheumatoid Arthritis: Post-Hoc Analysis of Planetra Study

Abstract

Background/Purpose:

Rheumatoid Arthritis (RA) is a chronic inflammatory disorder affecting synovial joints. Multiple pro- and anti-inflammatory cytokine are thought to play a major role in the development of the disease. IL-37 is an anti-inflammatory cytokine which belongs to IL-1 family superfamily and regulates inflammation. We investigated the association of IL-37 with disease activity in RA patients, who were treated with infliximab for 30 weeks.

Methods:

Patients were recruited from the PLANETRA study (NCT01217086). Patients with active RA were treated with CT-P13 or infliximab originator (INX). We measured the serum levels of IL-37 at week 0 (baseline) and at 30 weeks after treatment. Other demographic, laboratory and clinical variables were evaluated simultaneously. Mann-Whitney or Wilcoxon signed rank test was performed to determine the difference between two groups and Spearman¡¯s correlation coefficient was used to test for correlations between to variables. The values described are the median values.

Results:

66 patients with active RA (53 females and 13 males, 54 White and 12 Asians) were analyzed and median age of patients was 50 years. Compared to baseline, all measured clinical and laboratory parameters and serum IL-37(from 46.1 to 25.2 pg/ml, p=0.011) were significantly reduced. There was a correlation between IL-37 and CRP at the time of screening, and IL37 correlated with ESR, CRP, DAS28-ESR, DAS28-CRP and PGAD at week 30. IL-37 levels at 30 weeks after treatment, were lower in patients with DAS28¡Â3.2 than in patients with DAS28>3.2 (DAS28-ESR; 0.0 in DAS28¡Â3.2, 30.6 in DAS28>3.2, p=0.002, DAS28-CRP; 0.0 in DAS28¡Â3.2, 34.3 in DAS28>3.2, p=0.010). IL-37 levels decreased significantly in the EULAR good & moderate response group (DAS28-ESR; 42.2 at week 0, 0.0 at week 30, p=0.006, DAS28-CRP; 44.8 at week0, 18.5 at week 30, p=0.001), but not in non-responder group. According to the median level of IL-37, CRP was higher in the high group (n=29) at screening, and CRP, ESR DAS28-ESR, DAS28-CRP, HAQ and PAP were higher in high group at week 30.

Conclusion:

Serum levels of IL-37 is elevated in active RA patients and is associated with disease activity measures of RA.