Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis

Arthritis Res Ther. 2016 Dec 13;18(1):294. doi: 10.1186/s13075-016-1190-z.


Background: Recent works have suggested a possible link between interleukin (IL)-33 and B-cell biology. We aimed to study the possible association between serum IL-33 detection and response to rituximab (RTX) in rheumatoid arthritis (RA) patients in different cohorts with an accurate enzyme-linked immunosorbent assay (ELISA).

Methods: Serum IL-33, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and high serum immunoglobulin (Ig)G levels were assessed in 111 RA patients receiving a first course of 2 g RTX (cohort 1) in an observational study and in 74 RA patients treated with the same schedule in routine care (cohort 2). Univariate and multivariate analyses identified factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks.

Results: At week 24, 84/111 (76%) and 54/74 (73%) patients reached EULAR response in cohorts 1 and 2, respectively. Serum IL-33 was detectable in only 33.5% of the patients. In the combined cohorts, the presence of RF or anti-CCP (odds ratio (OR) 3.27, 95% confidence interval (CI) 1.13-9.46; p = 0.03), high serum IgG (OR 2.32, 95% CI 1.01-5.33; p = 0.048), and detectable serum IL-33 (OR 2.40, 95% CI 1.01-5.72; p = 0.047) were all associated with RTX response in multivariate analysis. The combination of these three factors increased the likelihood of response to RTX. When serum IL-33 detection was added to seropositivity and serum IgG level, 100% of the patients with the three risk factors (corresponding to 9% of the population) responded to RTX (OR versus patients with none of the three risk factors 29.61, 95% CI 1.30-674.79; p = 0.034).

Conclusion: Detectable serum IL-33 may predict clinical response to RTX independently of, and synergistically with, auto-antibodies and serum IgG level.

Trial registration: NCT01126541 ; 18 May 2010.

Keywords: B-cell; Interleukin 33; Personalized medicine; Rheumatoid arthritis; Rituximab.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Biomarkers / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-33 / blood*
  • Male
  • Middle Aged
  • Rituximab / therapeutic use*
  • Treatment Outcome


  • Antirheumatic Agents
  • Biomarkers
  • IL33 protein, human
  • Interleukin-33
  • Rituximab

Associated data