Therapeutic response to leflunomide in combo therapy and monotherapy is associated to serum teriflunomide (A77 1726) levels

Sci Rep. 2022 Feb 3;12(1):1877. doi: 10.1038/s41598-022-05644-7.

Abstract

There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = - 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Cross-Sectional Studies
  • Crotonates / adverse effects
  • Crotonates / blood
  • Crotonates / therapeutic use*
  • Drug Monitoring
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxybutyrates / adverse effects
  • Hydroxybutyrates / blood
  • Hydroxybutyrates / therapeutic use*
  • Leflunomide / adverse effects
  • Leflunomide / blood
  • Leflunomide / therapeutic use*
  • Male
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / blood
  • Nitriles / therapeutic use*
  • Predictive Value of Tests
  • Remission Induction
  • Severity of Illness Index
  • Time Factors
  • Toluidines / adverse effects
  • Toluidines / blood
  • Toluidines / therapeutic use*
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Crotonates
  • Hydroxybutyrates
  • Nitriles
  • Toluidines
  • teriflunomide
  • Leflunomide