The College of Pharmacy discussed the PhD dissertation entitled “The Effect of FCGR3A Gene Polymorphism on The Degree of Response and Formation of Autoantibodies to Infliximab in Iraqi Patients with Inflammatory Bowel Disease” by the student Ahmad Kadhum Abd and his supervisor, Assistant Professor Dr. Samer Emad Mohammed in the clinical pharmacy Department.
The study aimed to evaluate the association between FCGR3A gene polymorphisms and infliximab drug level, immunogenicity, and clinical outcomes in Iraqi IBD patients. Specific objectives included determining genotype distributions, assessing anti-drug antibody development patterns, evaluating clinical response correlations, and comparing therapeutic drug monitoring parameters between disease subtypes.
This cross-sectional cohort study enrolled 87 Iraqi patients (44 ulcerative colitis, 43 Crohn’s disease) receiving maintenance infliximab therapy. Clinical disease activity was assessed using validated indices (partial Mayo score for UC, CDAI for CD). Pre-infusion blood samples were analyzed for complete blood counts, inflammatory markers (ESR, CRP), infliximab trough levels, and anti-drug antibodies using ELISA methodology. FCGR3A polymorphisms (rs396991, rs449443, rs396716, rs443082) were determined via PCR sequencing. Statistical analyses included logistic regression modeling to evaluate genotype-phenotype associations.
The results showed that clinical remission was achieved in 40.9% of UC patients (median 98.4 weeks) and 48.8% of CD patients (median 66.7 weeks), aligning with long‑term trial data. Anti-drug antibodies were detected in 27.3% (UC) and 27.9% (CD) as total ATI, and in 11.4% and 9.3% as free ATI. Over 75% of patients had subtherapeutic infliximab levels (<3 µg/mL), with only 22.7% (UC) and 25.6% (CD) reaching target concentrations despite combination therapy. The FCGR3A rs396991 polymorphism showed disease‑specific pharmacogenetic effects: in UC, the AC genotype correlated with low trough levels (median 0.34 µg/mL) and high ATI (53.3%), while CC carriers achieved optimal exposure (55.6% ≥3 µg/mL; 22.2% ATI). In CD, the AC genotype was protective (41.7% ≥3 µg/mL, lowest ATI), and the AA genotype was linked to better hematologic indices. Logistic regression confirmed in UC that the AA genotype reduced odds of achieving target levels (OR = 0.27, p = 0.019) but increased risk of ATI development (OR = 8.50 total; OR = 18.00 free).
The study recommended implantation of therapeutic drug monitoring and regular disease activity assessment as well as the importance of encouraging pharmacogenetic studies in Iraq.
