Patient characteristics influence the choice of biological drug in RA, and will make non-TNFi biologics appear more harmful than TNFi biologics

Ann Rheum Dis. 2018 May;77(5):650-657. doi: 10.1136/annrheumdis-2017-212395. Epub 2017 Dec 13.

Abstract

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.

Keywords: dmards (biologic); epidemiology; health services research; outcomes research; rheumatoid arthritis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept / therapeutic use
  • Adult
  • Age Distribution
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / psychology
  • Biological Products / adverse effects
  • Biological Products / therapeutic use*
  • Choice Behavior*
  • Drug Substitution / psychology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Registries
  • Regression Analysis
  • Risk Assessment
  • Rituximab / therapeutic use
  • Severity of Illness Index
  • Sex Distribution
  • Social Class
  • Sweden
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Biological Products
  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Abatacept
  • tocilizumab