Incidence and risk factors of discontinuation of tofacitinib and biologic disease-modifying anti-rheumatic drugs among patients with rheumatoid arthritis: A population-based cohort study

Clin Rheumatol. 2024 Dec;43(12):3625-3637. doi: 10.1007/s10067-024-07161-6. Epub 2024 Oct 11.

Abstract

To investigate the incidence of the discontinuation among tofacitinib and biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). This retrospective population-based cohort study included 5,008 RA patients who initiated treatment with either tofacitinib or bDMARDs (etanercept, adalimumab, golimumab, tocilizumab, or abatacept) between January 1, 2014, and December 31, 2020. We conducted Cox proportional hazards regression and subsequent time-dependent regression to assess the risk of drug discontinuation, with adjustments for potential variables. The highest drug discontinuation rate was observed with etanercept (43.27%), while the lowest was with tofacitinib (21.8%). Tofacitinib was associated with a significantly lower risk of discontinuation compared to etanercept (HR: 0.67, 95% CI: 0.57-0.80) and other bDMARDs. Higher steroid dosage and the presence of concomitant connective tissue diseases were significant risk factors for drug discontinuation. Conversely, the use of methotrexate was associated with a reduced risk of discontinuation. Tofacitinib demonstrated a lower risk of drug discontinuation compared to TNFi, with the risk factors for discontinuation including higher steroid dosage and concomitant connective tissue diseases. The study highlights the importance of considering several potential risk factors in drug discontinuation. Key Points • Non-TNFi biologic agents demonstrated better drug retention than TNFi among patients diagnosed with rheumatoid arthritis, with tofacitinib showing the lowest discontinuation rate (21.8%), underscoring its potential for superior drug retention in rheumatoid arthritis management. • Several factors were associated with drug discontinuation: higher steroid dosage and concomitant connective tissue diseases were linked to a higher discontinuation rate, whereas the concomitant use of methotrexate was associated with a lower risk of discontinuation.

Keywords: Biological agents; Drug discontinuation; Drug persistence; Rheumatoid arthritis; TNF inhibitors; Tofacitinib.

MeSH terms

  • Abatacept / administration & dosage
  • Abatacept / therapeutic use
  • Adalimumab / administration & dosage
  • Adalimumab / therapeutic use
  • Adult
  • Aged
  • Antirheumatic Agents* / administration & dosage
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Biological Products / administration & dosage
  • Biological Products / therapeutic use
  • Etanercept / administration & dosage
  • Etanercept / therapeutic use
  • Female
  • Humans
  • Incidence
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use
  • Middle Aged
  • Piperidines* / administration & dosage
  • Piperidines* / therapeutic use
  • Pyrimidines* / administration & dosage
  • Pyrimidines* / therapeutic use
  • Retrospective Studies
  • Risk Factors

Substances

  • tofacitinib
  • Pyrimidines
  • Piperidines
  • Antirheumatic Agents
  • Etanercept
  • Methotrexate
  • Biological Products
  • Adalimumab
  • Abatacept