S863 Impact of Race on ANTI-TNF Immunogenicity in Patients with Inflammatory Bowel Disease

Abstract

Introduction: Immunogenicity is a major contributor to anti-tumor necrosis factor (anti-TNF) treatment failure in inflammatory bowel disease (IBD). Immunomodulator and anti-TNF combination therapy is associated with a decreased risk of immunogenicity. Anti-TNF immunogenicity was recently linked to HLA-DQA1*05 genotype. This study aims to determine the impact of race on rates of immunogenicity and treatment outcomes of IBD pts on anti-TNF combination therapy. Methods: This was a single-center, retrospective study of IBD pts who have been treated with immunomodulators and anti-TNF combination therapy between 2012 and 2020. Our primary outcomes were the rates of anti-TNF antibody formation and mean anti-TNF drug levels between Caucasian group(CG) and non-Caucasian group(NCG) on combination therapy. Secondary outcomes included steroid-free clinical remission (SFCR), endoscopic remission (ER) (absence of ulcers/erosions in CD and Mayo endoscopic score ≤ 1 for UC), & normal serum C-reactive protein (CRP) (defined as ≤ 5. mg/L). Continuous variables were analyzed using unpaired student’s t-test. Categorical variables were analyzed using a chi-square test. Results: A total of 124 pts were included (CD; 68.5%, UC; 27.4%, indeterminate colitis; 3.2%, pouchitis; 0.9%). The median age was 32 years (range 13-69), and 54.8% were male. A total of 87 pts were on infliximab & 37 pts were on adalimumab. Combination therapy with thiopurine was employed in 87.1% while 12.9% were on methotrexate. A total of 85 pts were self-identified as Caucasian. There were no significant differences between CG vs NCG in terms of baseline and disease characteristics (Table). Anti-TNF antibody formation was observed in 32.9% of pts in the CG, and 20.5% of pts in the NCG (p=0.16). Mean anti-TNF drug levels were lower in the CG at 15.4 ± 14.5 µg/mL vs. the NCG at 22.7 ± 15.1 µg/mL (p=0.01). SFCR was observed in 61.2% vs. 58.9% (p=0.82) in CG vs. NCG, respectively. In CG 42.4% vs. 33.3% in NCG (p=0.34) discontinued anti-TNF treatment during follow-up. ER was observed in 45.9 % vs 51.3% (p=0.44), and normal CRP was observed in 51.8% vs. 58.9% (p=0.28) in CG vs. NCG, respectively. Conclusion: In our cohort, Caucasian pts on anti-TNF combination therapy for IBD had significantly lower anti-TNF drug levels as compared to the non-Caucasian group. However, there was no significant difference between rates of anti-TNF antibody formation and clinical outcomes between the groups. Larger studies are needed to clarify impact of race on anti-TNF therapy. Table 1. - Comparison of Characteristics Between Caucasian vs. Non-Caucasian Race Caucasian (n=85), n (%), mean (SD) Non-Caucasian (n=39), n (%), mean (SD) P-value 34.7 (13.7) 34.7 (11.7) 0.98 47 (55.3) 21 (53.9) 0.88 7 (8.2) 6 (15.4) 0.23 36.4 (27.1) 41.9 (31.8) 0.35 0.07 53 (62.4) 32 (82.1) 29 (34.1) 5 (12.8) 2 (2.3) 2 (5.1) 1 (1.2) 0 21 (24.7) 15 (38.5) 0.12 24 (28.2) 14 (35.9) 0.81 10 (11.8) 6 (15.4) 0.77 61 (71.8) 26 (66.7) 0.56 69 (81.2) 29 (74.4) 0.39 12.5 (21.4) 6.8 (7.6) 0.15 3.9 (0.6) 4.1 (0.4) 0.16 *Data missing for 68 patients.**Data missing for 42 patients.Abbreviations: Anti TNF, anti-tumor necrosis factor; CRP, C reactive protein.