title: Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab.
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-α; and IL-6. TCZ and anti-TCZ antibodies were detected using LISA-TRACKER Duo TCZ. TCZ levels of <10 µg/mL were considered low and >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 and the 42 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-α: 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.
authors.affiliation: Rheumatology Unit, Ospedale San Giovanni di Dio, Florence, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Benucci
authors.affiliation: Allergology and Immunology Laboratory, Ospedale San Giovanni di Dio, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Meacci
authors.affiliation: Allergology and Immunology Laboratory, Ospedale San Giovanni di Dio, Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Grossi
authors.affiliation: Allergology and Immunology Laboratory, Ospedale San Giovanni di Dio, Florence, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Infantino
authors.affiliation: Allergology and Immunology Laboratory, Ospedale San Giovanni di Dio, Florence, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Manfredi
authors.affiliation: Allergology and Immunology Laboratory, Ospedale San Giovanni di Dio, Florence, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bellio
authors.affiliation: Allergology and Immunology Laboratory, Ospedale San Giovanni di Dio, Florence, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Bellio
authors.affiliation: Rheumatology Unit, Ospedale San Giovanni di Dio, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Li Gobbi
authors.affiliation: Rheumatology Unit, University of Pisa, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bazzichi
authors.affiliation: Internal Medicine and Rheumatology Unit, University of Salerno, Salerno, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Moscato
authors.affiliation: Internal Medicine and Rheumatology Unit, University of Salerno, Salerno, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Caputo
authors.affiliation: Rheumatology Unit, Salvatore Maugeri Foundation, Mantua, Italy.
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Saviola
authors.affiliation: Rheumatology Unit, Ospedale Luigi Sacco, Milan, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Talotta
authors.affiliation: Rheumatology Unit, Ospedale Luigi Sacco, Milan, Italy.
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Sarzi-Puttini
authors.affiliation: IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Atzeni
keywords: TCZ drug level; antibodies anti-TCZ; tocilizumab