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FRI0247 Serum level of interleukin 33, a novel independent predictive biomarker of clinical response to rituximab in rheumatoid arthritis: results from the smart trial
  1. J. Sellam1,
  2. S. Rouanet2,
  3. H. Hendel-Chavez3,
  4. S. Marion-Thore4,
  5. C. Miceli-Richard5,
  6. B. Combe6,
  7. J. Sibilia7,
  8. X. Le Loët8,
  9. J. Tebib9,
  10. G. Chiocchia4,
  11. R. Jourdan2,
  12. M. Dougados10,
  13. Y. Taoufik3,
  14. X. Mariette5
  1. 1Rheumatology, Saint-Antoine Hospital, Univ Paris 6, Paris
  2. 2ROCHE, Boulogne-Billancourt
  3. 3Biological Immunology, Bicêtre Hospital, Univ Paris-Sud, Le Kremlin Bicêtre
  4. 4Institut Cochin, INSERM U1016, Paris
  5. 5Rheumatology, Univ Paris-Sud, Bicêtre Hospital, INSERM U1012, Le Kremlin Bicêtre
  6. 6Rheumatology, Lapeyronie Hospital, Univ Montpellier I, UMR5535, Montpellier
  7. 7Rheumatology, EA 3432, Strasbourg Hospital, Univ Strasbourg, Strasbourg
  8. 8Rheumatology Dpt, Rouen University Hospital & INSERM U905, Rouen
  9. 9Rheumatology, Lyon-Sud Hospital, Pierre-Bénite
  10. 10Paris-Descartes Univ; UPRES-EA 4058; Cochin Hospital Rheumatology B, Paris, France


Background Interleukin-33 (IL33) is a recently identified member of the interleukin-1 family that binds to its ST2 receptor expressed on various cells including mast cells, T-cells and also B1-cells in mice (1). IL-33 may activate B-cell, immunoglobulin secretion (IgA and IgG) and induce immunoglobulin class switching. We previously demonstrated in a whole-blood transcriptomic analysis performed in 69 patients (pts) with rheumatoid arthritis (RA) included in the SMART trial that baseline IL-33 mRNA upregulation was associated with subsequent clinical response to rituximab (RTX) (2).

Objectives To investigate whether baseline serum level of IL-33 may predict response to RTX in RA.

Methods Before treatment, serum level of IL-33 using ELISA and of B-cell activation biomarkers (rheumatoid factor [RF], anti-CCP antibodies, free light chains, IgG, IgA, IgM, and BAFF levels) were assessed in 205 RA pts participating to the SMART study and treated by a first course of RTX (1g day 1 and 15). Association between IL-33 level and RA features were determined. Results are presented in median and interquartiles. Uni and multivariate (clinical features, auto-antibodies status and IL33 level) analyses were performed to identify factors associated with a EULAR response at 24 weeks.

Results Serum IL-33 level was higher in pts with anti-CCP (anti-CCP+: 359 [87; 1619] vs anti-CCP-: 102 [39; 368]; p=0.001) and in those with RF (RF+: 365 [95; 1677] vs RF-: 131 [38; 602]; p=0.001). IL-33 level was not modulated by anti-TNF prior exposure (n=140) or current steroid use (n=161) (anti-TNF +: 216 [73; 978] vs anti-TNF -: 359 [78; 1874] pg/mL; NS) and steroid +: 254 [70; 1348] vs steroid -: 258 [79; 1345] pg/mL; NS). Serum IL-33 level was not correlated to DAS28-CRP (r=-0.04; NS). There were 146 (71%) responders (i.e. 44 good and 102 moderate). IL-33 level was associated with EULAR response (IL33 level: 361 [87; 1654] vs 131 [46; 475] pg/mL in responders and non responders to RTX, respectively; p=0.006). After adjustment on baseline DAS28-CRP, multivariate analysis indicated that IL33 level was independently associated with subsequent response to RTX (OR [95% CI]: 1.3 [1.02; 1.6]), as well as the presence of anti-CCP antibodies or RF (OR [95% CI]: 2.7 [1.2; 6.0]). The combination of the 2 parameters further increased the likelihood of response.

Conclusions Serum IL33 level is increased in RA pts with anti-CCP and/or RF. Moreover, we confirm our transcriptomic analysis and demonstrate for the first time that serum IL-33 level represents a novel simple useful biomarker predicting clinical response to RTX, independently of auto-antibodies status, which usually displays a strong impact on rituximab response. The role of the IL-33/ST2 axis in B-cell immunopathology in RA needs to be further addressed.


  1. Komai-Koma M et al. J Immunol 2011;186:2584-91

  2. Sellam et al ACR congress 2011

Disclosure of Interest: J. Sellam Grant/research support from: Roche, S. Rouanet Employee of: Roche, H. Hendel-Chavez: None Declared, S. Marion-Thore: None Declared, C. Miceli-Richard: None Declared, B. Combe Grant/research support from: Roche, J. Sibilia Grant/research support from: Roche, X. Le Loët Grant/research support from: Roche, J. Tebib Grant/research support from: Roche, G. Chiocchia: None Declared, R. Jourdan Employee of: Roche, M. Dougados Grant/research support from: Roche, Y. Taoufik: None Declared, X. Mariette Grant/research support from: Roche

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