An Economic Evaluation of Stopping Versus Continuing Tumor Necrosis Factor Inhibitor Treatment in Rheumatoid Arthritis Patients With Disease Remission or Low Disease Activity: Results From a Pragmatic Open-Label Trial

Arthritis Rheumatol. 2018 Oct;70(10):1557-1564. doi: 10.1002/art.40546. Epub 2018 Aug 23.


Objective: To evaluate, from a societal perspective, the incremental cost-effectiveness of withdrawing tumor necrosis factor inhibitor (TNFi) treatment compared to continuation of these drugs within a 1-year, randomized trial among rheumatoid arthritis patients with longstanding, stable disease activity or remission.

Methods: Data were collected from a pragmatic, open-label trial. Cost-utility analysis was performed using the nonparametric bootstrapping method, and a cost-effectiveness acceptability curve was constructed using the net-monetary benefit framework, where a willingness-to-accept threshold (WTA) was defined as the minimal cost saved that a patient accepted for each quality-adjusted life year (QALY) lost.

Results: A total of 531 patients were randomized to the stop group and 286 patients to the continuation group. Withdrawal of TNFi treatment resulted in a >60% reduction of the total drug cost, but led to an increase of ∼30% in other health care expenditures. Compared to continuation, stopping TNFi resulted in a mean yearly cost saving of €7,133 (95% confidence interval [95% CI] €6,071, €8,234]) and was associated with a mean loss of QALYs of 0.02 (95% CI 0.002, 0.040). Mean saved cost per QALY lost and per extra flare incurred in the stop group compared to the continuation group was €368,269 (95% CI €155,132, €1,675,909) and €17,670 (95% CI €13,650, €22,721), respectively. At a WTA of €98,438 per QALY lost, the probability that stopping TNFi treatment is cost-effective was 100%.

Conclusion: Although an official WTA is not defined, the mean saved cost of €368,269 per QALY lost seems acceptable in The Netherlands, given existing data on willingness to pay.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / economics*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / economics*
  • Cost-Benefit Analysis
  • Drug Costs / statistics & numerical data*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Pragmatic Clinical Trials as Topic
  • Quality-Adjusted Life Years
  • Statistics, Nonparametric
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Withholding Treatment / economics*


  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha

Associated data

  • NTR/NTR3112