AB0484 TROUGH LEVELS OF TNF-Α INHIBITORS AND THEIR IMMUNOGENICITY IN THE TREATMENT OF RHEUMATIC DISEASES AND INFLAMMATORY BOWEL DISEASES
Authors: T. Nuriakhmetova, I. K. Valeeva, J. Shevnina, D. Abdulganieva
Journal: Annals of the Rheumatic Diseases (2021)

Background: The features of the underlying immune-mediated disease can affect the efficacy, pharmacokinetics and immunogenicity of the biologic agents, which are among the important predictors of loss of response to TNF-α inhibitors (TNFi). Objectives: To compare the frequency of TNFi low trough levels and their immunogenicity in the treatment of rheumatic diseases (RD) (ankylosing spondylitis (AS) and rheumatoid arthritis (RA)) and inflammatory bowel diseases (IBD) (Crohn’s disease (CD) and ulcerative colitis (UC)). Methods: Among 120 patients (40 with AS (33.3%), 19 with RA (15.8%), 42 with CD (35%), and 19 with UC (15.8%)), trough level of infliximab (INX) (n=36, 30%), adalimumab (ADM) (n=45, 37.5%) and certolizumab pegol (CZP) (n=39, 32.5%) and the level of anti-drug antibodies (ADAb) were measured in the serum samples drawn directly before the planned drug administration. Results: Low drug level (below 0.5 μg/mL for INX 1 , 4.9 µg/ml for ADM 2 , and 20 µg/l for CZP 3 ) was found in 54 (45%) patients: in 33 (55.9%) patients with RD and 21 (34.4%) patients with IBD. In the RD group, low drug trough level was observed more often than in IBD (55.9% vs 34.4%, OR 2.418, 95% CI 1.157 to 5.052, p=0.018). Only in UC was there a relationship between the received low dose of the drug (up to 200 mg of INX, 40 mg of ADM, and 200 mg of CZP) and its low level in the serum (p=0.026). Among the additional factors associated with a low TNFi level, lower dose of concomitant therapy at the time of a biologic initiation (66.7% vs 20.8%, OR 7.6, 95% CI 1.388 to 41.617, p=0.033) and the absence of pseudopolyps (78.9% vs 21.1%, p=0.045) were found in IBD, and in case of RD these factors included the age of 30 to 45 years (72.7% vs 41.9%, OR 3.692, 95 % CI 1.136 to 12.0, p=0.026), the absence of comorbidities (58.6% vs 41.4%, OR 3.44, 1.09 to 10.858, p=0.032) and male gender (78.8% vs 50% in women, OR 3.714, 95% CI 1.194 to 11.552, p=0.02). ADAb were detected in 29 (24.2%) patients (7 to INX (19.4%), 8 (17.8%) to ADM, 14 (35.9%) to CZP), 23 (79.3%) of which had also a concomitant low trough level of the drug. There were no significant differences in the frequency of ADAb formation between the pathologies. In the AS group, antibodies to CZP were detected in all patients with a low level of the biologic, while only in 25% of patients receiving ADM, a low level was associated with the formation of ADAb (p=0.019). In addition, among patients with AS, ADAb were detected only in those patients who did not take prednisone at the time of blood serum sampling (100% vs 37.9%, p=0.037). Conclusion: Low level of TNFi is more common in RD than in IBD. For each group, the factors associated with a low trough level of TNFi were identified. There were no significant differences in the frequency of ADAb formation between nosologies. References: [1]Steenholdt C, Bendtzen K, Brynskov J, et al. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn’s disease. Scand J Gastroenterol 2011; 46: 310–318. [2]Bartelds GM, Krieckaert CL, Nurmohamed MT, van Schouwenburg PA, Lems WF, Twisk JW, Dijkmans BA, Aarden L, Wolbink GJ. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305:1460–1468. doi: 10.1001/jama.2011.406. [3]Gehin, J.E., Goll, G.L., Warren, D.J. et al. Associations between certolizumab pegol serum levels, anti-drug antibodies and treatment response in patients with inflammatory joint diseases: data from the NOR-DMARD study. Arthritis Res Ther 21, 256 (2019). https://doi.org/10.1186/s13075-019-2009-5 Disclosure of Interests: Tatiana Nuriakhmetova Grant/research support from: A grant to purchase reagents for scientific research from Novartis Pharmaceuticals, Ildariya Khairullovna Valeeva: None declared., Jana Shevnina: None declared., Diana Abdulganieva: None declared.