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Original article
Comparative effectiveness of subcutaneous tocilizumab versus intravenous tocilizumab in a pan-European collaboration of registries
  1. Kim Lauper1,2,
  2. Denis Mongin1,
  3. Florenzo Iannone3,
  4. Eirik Klami Kristianslund4,
  5. Tore K Kvien4,
  6. Dan Nordström5,
  7. Karel Pavelka6,
  8. Manuel Pombo-Suarez7,
  9. Ziga Rotar8,
  10. Maria Jose Santos9,
  11. Catalin Codreanu10,
  12. Galina Lukina11,
  13. Delphine S Courvoisier1 and
  14. Cem Gabay1,2
  1. 1 Division of Rheumatology, Geneva University Hospitals, Geneva, Switzerland
  2. 2 SCQM Registry, Zurich, Switzerland
  3. 3 Interdisciplinary Department of Medicine, Rheumatology Unit, GISEA, University Hospital of Bari, Bari, Italy,
  4. 4 Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  5. 5 Department of Medicine, ROB-FIN, Helsinki University Hospital and Helsinki University, Helsinki, Finland
  6. 6 Institute of Rheumatology, Prague and Clinic of Rheumatology Charles University, Prague, Czech Republic
  7. 7 Rheumatology Unit, Clinical University Hospital, University of Santiago de Compostela, Santiago de Compostela, Spain
  8. 8 Department of Rheumatology, BioRx.si, University Medical Centre Ljubljana, Ljubljana, Slovenia
  9. 9 Rheumatology Department, on behalf of Reuma.pt, Hospital Garcia de Orta, Almada, Portugal
  10. 10 Center of Rheumatic Diseases, University of Medicine and Pharmacy, Bucharest, Romania
  11. 11 ARBITER, Institute of Rheumatology, Moscow, Russian Federation
  1. Correspondence to Dr Kim Lauper; Kim.lauper{at}hcuge.ch

Abstract

Objective To compare the real-word effectiveness of subcutaneous tocilizumab (TCZ-SC) and intravenous tocilizumab (TCZ-IV) in rheumatoid arthritis (RA).

Methods Patients with RA with TCZ from eight European registries were included. Drug retention was compared using unadjusted Kaplan-Meier and Cox models adjusted for baseline patient, disease and treatment characteristics, using a strata term for year of treatment initiation and country of registry. The proportions of patients achieving Clinical Disease Activity Index (CDAI) remission and low disease activity (LDA) at 1 year were compared using samples matched on the same covariates and corrected for attrition using LUNDEX.

Results 3448 patients were retrieved, 2414 with TCZ-IV and 1034 with TCZ-SC. Crude median retention was 3.52 years (95% CI 3.22 to 3.85) for TCZ-IV and 2.12 years for TCZ-SC (95% CI 1.88 to 2.38). In a country-stratified and year of treatment initiation–stratified, covariate-adjusted analysis, hazards of discontinuation were similar between TCZ-SC and TCZ-IV treated patients (HR 0.93, 95% CI 0.80 to 1.09). The average adjusted CDAI change at 1 year was similar in both groups (−6.08). After matching, with 560 patients in each group, CDAI remission corrected for attrition at 1 year was also similar between TCZ-SC and TCZ-IV (10.4% in TCZ-IV vs 12.8% in TCZ-SC (difference: 2.4%, bootstrap 95% CI −2.1% to 7.6%)), but CDAI LDA was lower in TCZ-IV patients: 41.0% in TCZ-IV versus 49.1% in TCZ-SC (difference: 8.0 %; bootstrap 95% CI 2.4% to 12.4%).

Conclusion With similar retention and effectiveness, TCZ-SC is an adequate alternative to TCZ-IV for RA. When possible, considering the costs of the TCZ-IV route, TCZ-SC should be the preferred mode of administration.

  • rheumatoid arthritis
  • biological therapies
  • DMARDs
  • tocilizumab
  • subcutaneous
  • intravenous
  • epidemiology

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors All the authors have provided substantial contributions to the conception or design of the work, the acquisition of the data and the interpretation of data. KL and DSC performed the statistical analysis. KL, DSC, DM and CG made the first draft. All the other authors participated in the final drafting of the work or revising it critically for important intellectual content. All authors contributed to the final approval of the version published.

  • Funding The TOCERRA collaboration is funded by Roche. Clinical work in Czech Republic was partially supported by the project from the Ministry of Health for conceptual development of research organization MZ00023728 (Institute of Rheumatology). ROB-FIN is funded by AbbVie, Hospira, BMS, MSD, Pfizer, Roche and UCB. NOR-DMARD was previously supported with research funding to Diakonhjemmet Hospital from AbbVie, BMS, MSD/Schering-Plough, Pfizer/Wyeth, Roche and UCB. Reuma.pt is supported by unrestricted grants from Abbvie, Biogen, Celgene, MSD, Roche, Sanofi and Pfizer. BioRx.si has received funding for clinical research paid to Društvo za razvoj revmatologije from AbbVie, Roche, Medis, MSD and Pfizer. BIOBADASER has received funding from Fundacion Española de Reumatología, the Spanish Medicines and Health Products Agency (Agencia Española del Medicamento y Productos Sanitarios) and equal grants from pharmaceutical companies (AbbVie, Pfizer, Roche, Schering‐Plough and BMS). Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) database is sponsored by public and industrial support (http://scqm.ch/en/sponsoren/).

  • Competing interests KL: none declared. DM: none declared. FI: none declared. EKK: none declared. TKK has received fees for speaking and/or consulting from AbbVie, BMS, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Orion Pharma, Pfizer, Roche, Sandoz and UCB, and received research funding to Diakonhjemmet Hospital from AbbVie, BMS, MSD, Pfizer, Roche and UCB. DN benefited from grant and research support from AbbVie, BMS, MSD, Pfizer, Roche and UCB, and has received fees for speaking and/or consulting for AbbVie, BMS, MSD, Roche, UCB and Pfizer. KP benefited from grant and research support from AbbVie, Roche, Medis, MSD and Pfizer, and has received fees for speaking and/or consulting for AbbVie, Roche, Amgen, MSD, BMS, UCB and Egis. MP-S: none declared. ZR: none declared. MJS: none declared. CC: has received speaker and consulting fees from AbbVie, Amgen, Angellini, Astra Zeneca, BMS, Egis, MSD, Pfizer, Richter, Roche, Sanofi, Servier, Teva, UCB and Zentiva. GL has received fees for consulting for BMS, Roche, MSD, AbbVie and Pfizer. DSC has received consulting fees from BMS, Pfizer and Janssen. CG has received fees for speaking and/or consulting from AbbVie, BMS, Roche, Pfizer, Celgene, MSD, Janssen Cilag, Amgen and UCB, and received research funding from Roche, AbbVie, MSD and Pfizer.

  • Patient consent Obtained.

  • Ethics approval Geneva Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All the data belong to the registries. Anonymised data can be shared as long as agreements are made with all participating registries.

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