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Comparative effectiveness of tocilizumab versus TNF inhibitors as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis after the use of at least one biologic disease-modifying antirheumatic drug: analyses from the pan-European TOCERRA register collaboration
  1. Kim Lauper1,2,
  2. Dan C Nordström3,
  3. Karel Pavelka4,
  4. Maria Victoria Hernández5,
  5. Tore K Kvien6,
  6. Eirik Klami Kristianslund6,
  7. Maria Jose Santos7,
  8. Žiga Rotar8,
  9. Florenzo Iannone9,
  10. Catalin Codreanu10,
  11. Galina Lukina11,
  12. Sara L Gale12,
  13. Khaled Sarsour12,
  14. Yves Luder13,
  15. Delphine Sophie Courvoisier1,
  16. Cem Gabay1,2
  1. 1Geneva University Hospitals, Geneva, Switzerland
  2. 2SCQM Registry, Zurich, Switzerland
  3. 3ROB-FIN Helsinki University Hospital and Helsinki University, Helsinki, Finland
  4. 4Charles University, Prague, Czech Republic
  5. 5Rheumatology Department, Hospital Clinic Barcelona, Barcelona, Spain
  6. 6Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  7. 7Rheumatology Department, Hospital Garcia de Orta, on behalf of Reuma.pt, Almada, Portugal
  8. 8BioRx.si, University Medical Centre Ljubljana, Ljubljana, Slovenia
  9. 9GISEA, University Hospital of Bari, Bari, Italy
  10. 10Center of Rheumatic Diseases, University of Medicine and Pharmacy, Bucharest, Romania
  11. 11ARBITER, Institute of Rheumatology, Moscow, Russian Federation
  12. 12Genentech, South San Francisco, California, USA
  13. 13F. Hoffmann-La Roche AG, Basel, Switzerland
  1. Correspondence to Prof Cem Gabay, Division of Rheumatology, Geneva University Hospitals, Geneva 1205, Switzerland; cem.gabay{at}hcuge.ch

Abstract

Objective To compare the effectiveness of tocilizumab (TCZ) and tumour necrosis factor (TNF) inhibitors (TNFi) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) after the use of at least one biologic DMARD (bDMARD).

Methods We included patients with RA having used at least one bDMARD from 10 European registries. We compared drug retention using Kaplan-Meier and Cox models and Clinical Disease Activity Index (CDAI) change over time with mixed-effects models for longitudinal data. The proportions of CDAI remission and low disease activity (LDA) at 1 year were compared using LUNDEX correction.

Results 771 patients on TCZ as monotherapy (TCZ mono), 1773 in combination therapy (TCZ combo), 1404 on TNFi as monotherapy (TNFi mono) and 4660 in combination therapy (TNFi combo) were retrieved. Crude median retention was higher for TCZ mono (2.31 years, 95% CI 2.07 to 2.61) and TCZ combo (1.98 years, 95% CI 1.83 to 2.11) than TNFi combo (1.37 years, 95% CI 1.30 to 1.45) and TNFi mono (1.31 years, 95% CI 1.18 to 1.47). In a country and year of treatment initiation-stratified, covariate-adjusted analysis, hazards of discontinuation were significantly lower among patients on TCZ mono or combo compared with patients on TNFi mono or combo, and TNFi combo compared with TNFi mono, but similar between TCZ mono and combo. Average adjusted CDAI change was similar between groups. CDAI remission and LDA rates were comparable between groups.

Conclusion With significantly longer drug retention and similar efficacy to TNFi combo, TCZ mono or combo are reasonable therapeutic options in patients with inadequate response to at least one bDMARD.

  • rheumatoid arthritis
  • DMARDS (biologic)
  • methotrexate
  • anti-tnf

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Footnotes

  • Handling editor Josef S Smolen

  • 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. DSC and KL performed the statistical analysis. KL, DSC 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.

  • Competing interests Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) database is sponsored by public and industrial support (http://scqm.ch/en/sponsoren/). DCN 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. ROB-FIN is funded by AbbVie, Hospira, BMS, MSD, Pfizer, Roche and UCB. 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. Clinical work in Czech Republic was supported by the project from the Ministry of Health for conceptual development of research organisation 023728 (Institute of Rheumatology). 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. 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, MSD, Roche and Pfizer. ŽR: none declared. BioRx.si has received funding for clinical research paid to Društvo za razvoj revmatologije from AbbVie, Roche, Medis, MSD and Pfizer. CC: has received speaker and consulting fees from AbbVie, Amgen, Angellini, AstraZeneca, BMS, Egis, MSD, Pfizer, Richter, Roche, Sanofi, Servier, Teva, UCB, Zentiva. GL has received fees for consulting for BMS, Roche, MSD, AbbVie and Pfizer. The ARBITER registry is supported by a non-commercial partnership with ‘Equalrights to life’. SLG and KS are employees of Genentech. YL is an employee of F. Hoffmann-La Roche. 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, UCB and received research funding from Roche, AbbVie, MSD and Pfizer.

  • Patient consent Not required.

  • Ethics approval Approval of each local ethical committee for the collection of clinical data in each registry.

  • 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.

  • Presented at This manuscript is based on work previously presented at EULAR 2017 congress and published as a conference abstract: Lauper K, Nordström D, Pavelka K, et al. SAT0206 Retention of tocilizumab as monotherapy versus TNF inhibitors with conventional synthetic DMARDS in rheumatoid arthritis patients with inadequate response to TNF inhibitors: a study from the TOCERRA collaboration. Annals of the Rheumatic Diseases 2017;76:850–851.

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