Levels of interleukin-1 beta can predict response to tocilizumab therapy in rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab therapy) study

Rheumatol Int. 2016 Mar;36(3):349-57. doi: 10.1007/s00296-015-3379-x. Epub 2015 Oct 5.

Abstract

Predicting the responses of patients with rheumatoid arthritis (RA) to tocilizumab is difficult, because inflammatory markers such as C-reactive protein rapidly normalize regardless of clinical efficacy. We aimed to identify factors that could predict response to tocilizumab. Sixty-five patients completed 52 weeks of tocilizumab therapy. Serum fibrinogen, D-dimer and interleukin (IL)-1β levels were measured at baseline and after 4 weeks of therapy. Clinical responses to tocilizumab were assessed using disease activity score 28-erythrocyte sedimentation rate and the clinical disease activity index at baseline and after 52 weeks of therapy (UMIN Clinical Trials Registry No. UMIN000002246). Mean age was 60.5 years (range 22-85 years). Mean disease duration was 11.2 years (range 0-45 years). All patients had moderate-to-severe disease activity and were resistant to disease-modifying anti-rheumatic drugs and/or other biologics. Baseline IL-1β levels were significantly lower in responders than in non-responders (p = 0.045), but multiple logistic regression analysis found no significant difference (adjusted odds ratio 2.74; 95 % confidence interval 0.84-8.95; p = 0.096). Low D-dimer and IL-1β levels at 4 weeks predicted greater decrease in disease activity after 52 weeks of treatment (p = 0.005 and p < 0.001, respectively). Effects of tocilizumab at 52 weeks could be predicted from D-dimer and IL-1β levels after 4 weeks of tocilizumab treatment. These markers might be more useful than current inflammatory markers for early-stage prediction of response to tocilizumab in RA.

Keywords: Biomarker; D-dimer; Fibrinogen; Interleukin-1 beta; Predictor; Rheumatoid arthritis; Tocilizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis / blood
  • Arthritis / diagnosis
  • Arthritis / drug therapy*
  • Biomarkers / blood
  • Drug Monitoring / methods*
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Humans
  • Inflammation Mediators / blood*
  • Interleukin-1beta / blood*
  • Japan
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Predictive Value of Tests
  • Prospective Studies
  • Remission Induction
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • IL1B protein, human
  • Inflammation Mediators
  • Interleukin-1beta
  • fibrin fragment D
  • tocilizumab