Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab

The aim of this study was to evaluate the real-life immunogenicity of anti-drug antibodies, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab (TCZ). We evaluated 126 TCZ-treated patients With rheumatoid arthritis (16 males and 110 females; mean age 59 12 years, range 26-83; mean disease duration 11 5 years) with inadequate 12-week response to any synthetic and biological disease-modifying anti-rheumatic drugs, in a retrospective analysis. One-hundred and seven patients were treated with methotrexate mean dose 12.6 1.3 mg/week in combination with TCZ, 13 received TCZ monotherapy, and six received leflunomide 20 mg/day plus TCZ; all patients were treated with prednisone mean close 6.4 1.2 mg/day. They had a 28-joint Disease Activity Score (DAS28) of >3.2, an erythrocyte sedimentation rate (ESR) of >30 mm/hour, and CRP levels of >1.0 mg/di We evaluated at baseline and after 6 months of treatment: DAS28; rheumatoid factor (RF) IgM, IgA, and IgG; anti-citrullinated peptide antibody; ESR; CRP; INF-a, and IL-6. TCZ and antiTCZ antibodies were detected using LISA-TRACKER Duo Tcz.Tcz levels of <10 g/mL were considered low and >10 g/ml. high. After 6 months of treatment only one patient was positive for anti-TCZ antibodies. There were correlations between DAS28, ESR, and CRP and IL-6 levels in all patients. Comparison of the 84 patients with TCZ levels of <10 pg/mL and the 42 with TCZ levels of >10 1.1 g/mL showed the following differences: DAS28: 3.09 1.32 vs 2.78 1.32, P=0.0005; ESR: 27 14.8 vs 14 12 min/hour, P=0.0001; CRP: 1.47 1.05 vs 0.65 0.80 mg/dL, P=0.0086; INF-alpha: 10.2+/-1.2 vs 9.9+/-1.1 pg/mL, P=0.999; IL-6: 3.65+/-4.75 vs 3.62+/-4.41 pg/mL, P=0.97; anti-eitrullinated peptide antibody: 85.2 93.7 vs 86.7 90.3 IU/mL, P=0.94; RF IgM: 72.4 62.7 vs 68.3 61.6 IU/ML, 1)=0.754; RF IgA: 41.7 36.4 vs 47.8 42.1 U/mL, P=0.449; and RF IgG: 46.4 46.1 vs 59.3 58.2 U/mL, P=0.212. These findings show that the occurrence of anti-drug antibodies against TCZ is very rare and that there are statistically significant correlations between TCZ levels of >10 g/mI, and ESR, CRP levels, and DAS28.