AB0780 Association of low trough level of TNFi and their immunogenicity with efficacy in rheumatic diseases and inflammatory bowel diseases

Abstract

BackgroundThe immunogenicity of TNF-α inhibitors (TNFi) is known to affect the efficacy of these biologic drugs. No previous studies compared this effect head-to-head between different groups of immune-mediated diseases.ObjectivesTo compare the effect of immunogenicity of TNFi and their trough level on their efficacy in rheumatic diseases (RD) (ankylosing spondylitis (AS) and rheumatoid arthritis (RA)) and inflammatory bowel diseases (IBD) (Crohn’s disease (CD) and ulcerative colitis (UC)).Methods123 patients receiving infliximab (INX) (n=36, 29.3%), adalimumab (ADM) (n=49, 39.8%) and certolizumab pegol (CZP) (n=38, 30.9%) were included into the study. 70 (56.9%) of them had RD (50 (40.7%) with AS and 20 (16.3%) with RA) and 53 (43.1%) of them had IBD (38 (30.9%) with CD and 15 (12.2%) with UC). The specific criteria were used to assess the response to the treatment (ASAS20 for AS, EULAR for RA, CDAI for CD and Mayo Score for UC). Measurement of trough level of TNFi and the level of anti-drug antibodies (ADAb) was performed with the use of commercially available ELISA kits. The threshold of low trough level depended on the diseases based on the guidelines: 1 μg/mL for INX1 in RD group and 5 μg/mL for INX2 in IBD group, 5 µg/ml for ADM3, and 20 µg/l for CZP4.ResultsEfficacy of TNFi was 1.3 times more prevalent among patients with RD than among IBD patients (n=60, 85.7% vs n=35, 66%, OR 1.3, 95%CI 1.0 to 1.6, p=0.01). Rate of response to INX and ADM was comparable between the diseases while CZP was more efficient in RD (4.8% vs 35.3%, OR 1.5, 95%CI 1.0 to 2.0, p=0.031).Median trough levels of TNFi did not differ between the groups (p>0.05). Low level was determined in 26 (40.6%) patients with RD and 27 (45.8%) patients with IBD. Low level of TNFi most often was found in patients with UC (n=12, 80%, OR 5.6, 95%CI 1.493 to 20.999, p=0.006). Only INX low level was more prevalent in IBD patients than in RD (87% vs 46.2%, OR 5.7, 95%CI 1.1 to 29.2, p=0.046). The rate of low level of other TNFi was comparable between the groups (p>0.05). In RD group low level was associated with loss of response (80%, OR 6.0, 95%CI 1.2 to 30.7, p=0.036) while in IBD group no relation was found (51.4% vs 50%, p>0.05).Positive ADAb were determined in 22 (17.9%) patients: 14 (20%) in RD group and 8 (15.1%) in IBD group. TNFi did not differ significantly by the rate of ADAb-positivity (p>0.05). Association of loss of response with ADAb was observed in 4 (40%) patients with RD and 2 (11.1%) patients with IBD. Inefficacy of TNFi due to immunogenicity was 6 times more frequent in RA than in IBD (p>0.05). ADAb to INX (a chimeric antibody) were found only in patients with inefficacy (n=2, 66.7%, p=0.067). After exclusion of patients receiving ADM (a humanized antibody) 3 (75%) non-responders to INX or CZP with RD had positive ADAb while significantly less non-responders among IBD patients were ADAb-positive (n=2, 14.3%; OR 0.06, 95%CI 0.004 to 0.84, p=0.044).ConclusionMost of non-responders with RD had either low trough level of TNFi or ADAb, while in IBD group only half of cases of non-response could be attributed to the effect of ADAb or low trough level of TNFi.