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Subcutaneous tocilizumab alone or with a csDMARD in rheumatoid arthritis patients: subanalysis of Italian data from a multicenter phase IIIb/IV trial

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Abstract

To assess, in a setting close to real life, the efficacy and safety of weekly subcutaneous tocilizumab (TCZ-SC) 162 mg, alone or with a conventional synthetic DMARD (csDMARD), in moderate-to-severe RA patients with inadequate response to DMARDs or anti-TNFα drugs. This national, multicenter, open-label, phase IIIb trial is part of an umbrella study (TOZURA). Patients were treated for 52 weeks followed by 8 weeks drug-free to evaluate immunogenicity. The primary end point was the Clinical Disease Activity Index (CDAI) change from baseline at weeks 2 and 24. Other efficacy parameters, including sleep quality, and the safety and immunogenicity were also assessed up to week 52. Of 288 patients enrolled in 43 Italian centers, 78.8% received TCZ-SC (86.8% females; mean age 54.7 ± 12.1 years; mean disease duration 7.8 ± 7.5 years; DMARD-IRs 94.7%). Of these, 78.0% completed the 52-week period and 52.0% received concomitant methotrexate. TCZ-SC yielded a significant reduction in median CDAI from baseline already at week 2, which progressed up to week 24 and remained stable thereafter (P < 0.0001 at each time point). A significant, rapid, and sustained improvement of the other efficacy variables was also observed. Patients were deemed as ready for home administration after a median of 2.0 (range 1–8) administrations, with a rate (since the last visit) of 80.6% and 95.5% at weeks 2 and 52, respectively. TCZ-SC displayed low immunogenicity and no unexpected toxicities. TCZ-SC, alone or with a csDMARD, yielded rapid and sustained efficacy in DMARD/anti-TNFα-IR RA patients, with acceptable toxicity. Home administration seems feasible.

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Acknowledgements

We thank all the patients who participated in this study and the following investigators for their contribution: A. Afeltra (Clinical Medicine and Rheumatology, Policlinico Campus Bio-Medico di Trigoria, Roma), G. Bagnato (Center for Osteoporosis Prevention and Treatment, A.O.U. Policlinico G. Martino, Messina), L. Beretta (Allergology and Clinical Immunology, Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Milano), G. Bianchi (Rheumatology Unit, Ospedale La Coletta, Arenzano), M. Caminiti (Rheumatology Unit, A.O. Bianchi Melacrino Morelli, Reggio Calabria), G. Carlino (Rheumatology and Osteoporosis, ASL Lecce – Presidio Ospedaliero di Casarano, Casarano), G. D’Alessandro (Dept. Intenral Medicine, Rheumatology, Ospedali Riuniti di Foggia, Foggia), S. De Silva (Dept. General Medicine, Rheumatology, A.O. S. Giuseppe Moscati, Avellino), S. De Vita (Rheumatology Clinic, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine), O. Epis (Rheumatology, ASST Grande Ospedale Metropolitano Niguarda, Milano), C. Ferri (A.O.U. Policlinico di Modena, Modena), R. Foti (Rheumatology Unit, Clinica Medica Condorelli, A.O.U. Policlinico Vittorio Emanuele, Catania), E. Fusaro (Rheumatology, Azienda Ospedaliera San Giovanni Battista, Torino), A. Gabrielli (Medical Clinic, Ospedale Regionale Torrette, Ancona), R. Gerli (Department of Medicine, Rheumatology Unit, Ospedale S. Maria Misericordia, Perugia), R. Giacomelli (Dept. Internal Medicine, Rheumatology, Università degli Studi di L’Aquila, L’Aquila), W. Grassi (Rheumatology Clinic II, Ospedale Murri-Università Politecnica delle Marche, Jesi), L. Idolazzi (Dept. of Medicine, Rheumatology Unit, Azienda Ospedaliera Universitaria Borgo Trento, Verona), G. Lapadula (Rheumatology Unit, Policlinico, Università di Bari, Bari), M. Limonta (Day Hospital of Rheumatology, ASST Papa Giovanni XXIII, Bergamo), C. Lunardi (Division of Clinical and Experimental Immunology, Policlinico G.B. Rossi, Verona), N. Malavolta (U.O. Medicina Interna Borghi, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna), A. Mathieu (Rheumatology I, A.O.U. Policlinico Monserrato, Cagliari), N. Pappone (Salvatore Maugeri Foundation, Scientific Institute of Telese Terme, Telese Terme), G. Passiu (Rheumatology Unit, A.O.U. di Sassari, Sassari), R. Pellerito (Rheumatology Unit, Ordine Mauriziano Ospedale Umberto I, Torino), R. Perricone (Division of Rheumatology, Policlinico Tor Vergata, Roma), G. Pistone (Internal Medicine II, Arnas Ospedale Civico, Palermo), M.R. Pozzi (Rheumatology, ASST di Monza, Monza), P. Prandini (Immunohematology, Allergology and Rheumatology, Ospedale Civile La Memoria, Gavardo), A. Ricioppo (General Medicine, ASST di Vimercate, Vimercate), R. Russo (Division of Rheumatology, A.O. A. Cardarelli, Napoli), C. Salvarani (Rheumatology, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia), P.C. Sarzi-Puttini (Rheumatology, ASST Fatebenefratelli Sacco, Milano), M. Scarpellini (Rheumatology Unit, Ospedale G. Fornaroli, Magenta), B. Seriolo (Rheumatology, Università degli Studi di Genova – DIMI, Genova), S. Stisi (Division of Rheumatology, A.O. Rummo, Benevento), G. Valentini (Rheumatology, Policlinico Universitario-II Università di Napoli, Napoli), and F. Versace (Division of Rheumatology, Ospedale San Paolo, Savona). Medical writing support and editorial assistance was provided by Clara Ricci, PhD (Primula Multimedia S.r.L., Pisa) and funded by Roche S.p.A. (no grant number).

Funding

This work was sponsored by Roche S.p.A. The funding body had no influence on data acquisition, analysis, interpretation of the results, or writing of the manuscript.

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Authors and Affiliations

  1. Rheumatology Operative Unit, Department of Clinical and Experimental Medicine, University of Pisa, via Roma, 67, 56100, Pisa, Italy

    Laura Bazzichi

  2. Division of Rheumatology AOUC, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Francesca Nacci

  3. Rheumatology Unit, Ospedale G. Pini, Milan, Italy

    Luigi Sinigaglia

  4. Roche S.p.A, Monza, Italy

    Laura Bianchino

  5. Division of Rheumatology, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

    Roberto Caporali

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  1. Laura Bazzichi
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Correspondence to Laura Bazzichi.

Ethics declarations

The study was approved by each institutional ethics committee/review board, and all patients provided written informed consent. The study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.

Conflict of interest

Laura Bazzichi received fees for consultation from Roche, AbbVie, BMS, Pfizer, and Merck (less than $10,000 per year, overall); Francesca Nacci has nothing to disclose; Luigi Sinigaglia has nothing to disclose; Laura Bianchino is a Roche employee; and Roberto Caporali received fees for consultation and speaker’s activity from AbbVie, UCB, MSD, Italfarmaco, Roche, Pfizer, Lilly, and Novartis (less than $10,000 per year, overall).

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Significance and Innovations

• This is the first Italian study exploring the efficacy and safety of TCZ-SC, alone or with a csDMARD in DMARD/anti-TNFα-IR RA patients, in a setting close to real life.

• TCZ-SC, alone or with a csDMARD, yielded rapid and sustained efficacy, also in terms of sleep quality improvement, with acceptable toxicity.

• Home administration of TCZ-SC seems a feasible option.

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Bazzichi, L., Nacci, F., Sinigaglia, L. et al. Subcutaneous tocilizumab alone or with a csDMARD in rheumatoid arthritis patients: subanalysis of Italian data from a multicenter phase IIIb/IV trial. Clin Rheumatol 38, 841–849 (2019). https://doi.org/10.1007/s10067-018-4327-4

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  • DOI: https://doi.org/10.1007/s10067-018-4327-4

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