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Ann Rheum Dis. 2018 Sep;77(9):1276-1282. doi: 10.1136/annrheumdis-2017-212845. Epub 2018 May 5.

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.

Author information

1
Geneva University Hospitals, Geneva, Switzerland.
2
SCQM Registry, Zurich, Switzerland.
3
ROB-FIN Helsinki University Hospital and Helsinki University, Helsinki, Finland.
4
Charles University, Prague, Czech Republic.
5
Rheumatology Department, Hospital Clinic Barcelona, Barcelona, Spain.
6
Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
7
Rheumatology Department, Hospital Garcia de Orta, on behalf of Reuma.pt, Almada, Portugal.
8
BioRx.si, University Medical Centre Ljubljana, Ljubljana, Slovenia.
9
GISEA, University Hospital of Bari, Bari, Italy.
10
Center of Rheumatic Diseases, University of Medicine and Pharmacy, Bucharest, Romania.
11
ARBITER, Institute of Rheumatology, Moscow, Russian Federation.
12
Genentech, South San Francisco, California, USA.
13
F. Hoffmann-La Roche AG, Basel, Switzerland.

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.

KEYWORDS:

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

Conflict of interest statement

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.

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