title: Use and effectiveness of tocilizumab among patients with rheumatoid arthritis: an observational study from the British Society for Rheumatology Biologics Register for rheumatoid arthritis.
abstract: The aims of the present study are to describe the characteristics of rheumatoid arthritis (RA) patients selected for tocilizumab (TCZ), compare the "real-world" effectiveness of TCZ and tumour necrosis factor inhibitors (TNFi) when used as a first biologic and assess the influence of past biologic exposure/concurrent methotrexate (MTX) therapy on post-TCZ treatment outcomes. The British Society for Rheumatology Biologics Register (BSRBR-RA) is a prospective cohort study following RA patients starting biologics in the UK. This includes patients starting TCZ as first or subsequent biologic, alongside biologic-naïve patients starting TNFi. Six-month disease activity and 1-year drug survival were compared between biologic-naïve patients starting TCZ versus TNFi and first-line versus subsequent TCZ users and TCZ users with MTX versus without using regression models adjusted by propensity score. Two hundred seventeen patients started TCZ, and 2419 started TNFi as first biologic. Seven hundred seventy-seven started TCZ after other biologics. First-line TCZ users had a higher prevalence of pulmonary fibrosis and cancer history than TNFi users. The first-line TCZ users were more likely to achieve DAS28 remission at 6 months than first-line TNFi, but other improvement markers were similar. The treatment response at 6 months was similar between subsequent-line TCZ users and first-line users after adjusting for baseline patient differences. Concurrent MTX use was not associated with treatment response in either first- or subsequent-line TCZ users. TCZ has been primarily used as subsequent-line biologic in the UK. When used as first line, the response appears similar to that observed in patients starting TNFi, suggesting that clinical response alone should not decide between initial biologic therapies.
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Room 2.800 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.|Department of Rheumatology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-0034, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Kihara
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Room 2.800 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Davies
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Room 2.800 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Lianne
authors.initials: L
authors.lastname: Kearsley-Fleet
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Room 2.800 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Kath D
authors.initials: KD
authors.lastname: Watson
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Room 2.800 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Lunt
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Room 2.800 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester Partnership, Oxford Road, Manchester, M13 9WL, UK.
authors.forename: Deborah P M
authors.initials: DP
authors.lastname: Symmons
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Room 2.800 Stopford Building, Oxford Road, Manchester, M13 9PT, UK. kimme.hyrich@manchester.ac.uk.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester Partnership, Oxford Road, Manchester, M13 9WL, UK. kimme.hyrich@manchester.ac.uk.
authors.forename: Kimme L
authors.initials: KL
authors.lastname: Hyrich
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology; D011446:Prospective Studies; D011658:Pulmonary Fibrosis / Q000453:epidemiology; D012042:Registries; D012044:Regression Analysis; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D006113:United Kingdom
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C502936:tocilizumab; D008727:Methotrexate
keywords: Biological disease modifying anti-rheumatic drugs (bDMARDs); Observational study; Rheumatoid arthritis; Tocilizumab; Treatment outcome; Treatment selection