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Extended report
Patient characteristics influence the choice of biological drug in RA, and will make non-TNFi biologics appear more harmful than TNFi biologics
  1. Thomas Frisell1,
  2. Eva Baecklund2,
  3. Karin Bengtsson3,
  4. Daniela Di Giuseppe1,
  5. Helena Forsblad-d’Elia4,
  6. Johan Askling1,5
  7. on behalf of the ARTIS Study group
  1. 1 Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  2. 2 Rheumatology Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  3. 3 Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden
  4. 4 Department of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden
  5. 5 Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to Dr Thomas Frisell, Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm 17176, Sweden; thomas.frisell{at}


Objectives With the wide range of biological disease-modifying anti-rheumatic drugs (bDMARDs) available for treating rheumatoid arthritis (RA), and limited evidence to guide the choice for individual patients, we wished to evaluate whether patient characteristics influence the choice of bDMARD in clinical practice, and to quantify the extent to which this would bias direct comparisons of treatment outcome.

Methods Register-based study of all Swedish patients with RA initiating necrosis factor inhibitor (TNFi), rituximab, abatacept or tocilizumab in 2011–2015 as their first bDMARD (n=6481), or after switch from TNFi as first bDMARD (n=2829). Group differences in demographics, clinical characteristics and medical history were assessed in multivariable regression models. Predicted differences in safety and treatment outcomes were calculated as a function of patient characteristics, through regression modelling based on observed outcomes among patients with RA starting bDMARDs 2006–2010.

Results Patients starting non-TNFi were older than those starting TNFi, had lower socioeconomic status, higher disease activity and higher burden of diseases including malignancy, serious infections and diabetes. Differences were most pronounced at first bDMARD initiation. These factors were linked to treatment outcome independent of therapy, yielding worse apparent safety and effectiveness for non-TNFi biologics, most extreme for rituximab. Standardising to the age/sex distribution of the TNFi group reduced differences considerably.

Conclusions There was significant channelling of older and less healthy patients with RA to non-TNFi bDMARDs, in particular as first bDMARD. Whether this channelling represents a maximised benefit/risk ratio is unclear. Unless differences in age, medical history and disease activity are accounted for, they will substantially confound non-randomised comparative studies of available bDMARDs’ safety and effectiveness.

  • rheumatoid arthritis
  • dmards (biologic)
  • health services research
  • epidemiology
  • outcomes research

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 and the use is non-commercial. See:

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  • Handling editor Josef S Smolen

  • Contributors TF had full access to all data and takes responsibility for the integrity of the data and the accuracy of the data analysis. TF performed all analyses and drafted the first version of the manuscript. All authors were involved in drafting the study protocol before analyses, and reviewed the final manuscript for important intellectual contents.

  • Funding This study was supported by the Swedish Foundation for Strategic Research, Swedish Research Council, Swedish Cancer Society, Swedish Heart Lung Foundation, ALF funding collaboration between Karolinska Institute and Stockholm County, and the IMI funded EU project Be The Cure.

  • Competing interests ARTIS has entered into agreements with Abbvie, BMS, MSD, Lilly, Pfizer, Roche, Samsung Bioepis and UCB. Companies with products mentioned in this manuscript were given a courtesy review of the manuscript before publication, but were not involved in planning the study, performing the analysis or interpreting the results.

  • Ethics approval The Regional Ethical Review Board in Stockholm granted ethical approval (DNR: 2016/1986-32).

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

  • Data sharing statement Access to the national register data used for this study is granted on a restrictive basis, and may not be shared without additional specific permissions from the Swedish register-holding authorities.

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