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

Maurizio Benucci, F. Meacci, Valentina Grossi, M. Infantino, Mariangela Manfredi, Emanuele Bellio, Valerio Bellio, F. Li Gobbi, L. Bazzichi, P. Moscato, Dario Caputo, Gianantonio Saviola, R. Talotta, Piercarlo Sarzi-Puttini, Fabiola Atzeni

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Abstract

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 dose 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/dL. We evaluated at baseline and after 6 months of treatment: DAS28; rheumatoid factor (RF) IgM, IgA, and IgG; anti-citrullinated peptide antibody; ESR; CRP; TNF-a; and IL-6. TCZ and anti- TCZ antibodies were detected using LISA-TRACKER Duo TCZ. TCZ levels of 10 μg/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 μg/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 mm/hour, P=0.0001; CRP: 1.47±1.05 vs 0.65±0.80 mg/dL, P=0.0086; TNF-a: 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-citrullinated 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, P=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 μg/mL and ESR, CRP levels, and DAS28.

Original languageEnglish
Pages (from-to)53-58
Number of pages6
JournalBiologics: Targets and Therapy
Volume10
DOIs
Publication statusPublished - Mar 11 2016

Keywords

  • Antibodies anti-TCZ
  • TCZ drug level
  • Tocilizumab

ASJC Scopus subject areas

  • Oncology
  • Immunology and Allergy
  • Pharmacology (medical)
  • Gastroenterology
  • Rheumatology

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    Benucci, M., Meacci, F., Grossi, V., Infantino, M., Manfredi, M., Bellio, E., Bellio, V., Li Gobbi, F., Bazzichi, L., Moscato, P., Caputo, D., Saviola, G., Talotta, R., Sarzi-Puttini, P., & Atzeni, F. (2016). Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab. Biologics: Targets and Therapy, 10, 53-58. https://doi.org/10.2147/BTT.S97234