Association of polymorphisms in promoter region of TNF-α -238 and -308 with clinical outcomes in patients with immune-mediated inflammatory diseases on anti-TNF therapy

• Published in: Rheumatology international 2021-12, Vol.41 (12), p.2195-2203
• Main Authors: Miler, Marijana, Nikolac Gabaj, Nora, Ćelap, Ivana, Grazio, Simeon, Tomašić, Vedran, Bišćanin, Alen, Mitrović, Joško, Đerek, Lovorka, Morović-Vergles, Jadranka, Vrkić, Nada, Štefanović, Mario
• Format: Article
• Language: English
• Subjects: Adalimumab - administration & dosage; Adult; Aged; Biomarkers - analysis; Bowel disease; C-Reactive Protein - analysis; Clinical outcomes; Female; Genes and Disease; Humans; Inflammatory Bowel Diseases - drug therapy; Infliximab - administration & dosage; Leukocyte L1 Antigen Complex - analysis; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Polymorphism, Single Nucleotide; Prospective Studies; Remission Induction; Rheumatic Diseases - drug therapy; Rheumatology; TNF inhibitors; Tumor Necrosis Factor Inhibitors - administration & dosage; Tumor Necrosis Factor-alpha
• ISSN: 0172-8172; 1437-160X
• DOI: 10.1007/s00296-021-05016-w

The hypothesis of the study was that polymorphisms in promoter regions -238 and -308 of TNF-α could be associated with different clinical outcomes in inflammatory bowel diseases (IBD) and immune-mediated rheumatic diseases (IMRD). The aim was to examine the possible association of both polymorphisms with concentration of C-reactive protein (CRP) and fecal calprotectin (fCAL), onset of the remission and development of the ADA in patients on therapy with anti-TNF inhibitors. The prospective study was done in patients with IBD and IMRD on infliximab (IFX) or adalimumab (ADM). Patients were genotyped for TNF-α  -238 and -308 polymorphisms. The concentration of CRP, fCAL, IFX or ADM and antibodies to drugs were measured according to manufacturer’s instructions and followed-up for 6 or 12 months. Out of all patients ( N  = 112), number of patients in remission did not differ according to genotypes (for IBD patients P  = 0.509 vs 0.223; for IMRD patients P  = 0.541 vs 0.132 for TNF-α  -238 and -308, respectively). Initial CRP concentration was higher in IBD patients with TNF-α -308 GG than GA/AA genotypes in patients who failed to achieve remission [11.8 (4.4–39.6) vs 3.1 (1.5–6.5), P  = 0.033]. In IBD patients with remission, fCAL concentration after at least 6 months of therapy was higher in TNF-α -308 GG than in GA genotype [52 (25–552) vs 20 (20–20) µg/g, P  = 0.041]. Our results showed the association of TNF-α  -308 GG genotype with a higher concentration of CRP and fecal calprotectin in patients with inflammatory bowel diseases on IFX or ADM therapy. Clinical remission and development of antibodies to anti-TNF drugs were not associated with TNF-α  -238 and -308 polymorphisms.