Molecular Diagnosis & Therapy

, Volume 14, Issue 1, pp 43–48 | Cite as

Response to Rituximab and Timeframe to Relapse in Rheumatoid Arthritis Patients

Association with B-Cell Markers
  • Athina Pyrpasopoulou
  • Stella Douma
  • Areti Triantafyllou
  • Elisavet Simoulidou
  • Magda Samara
  • Efthymia Parapanisiou
  • Spyros Aslanidis
Short Communication

Abstract

Objective: Rituximab is used to deplete B cells and control disease activity, mainly in patients with rheumatoid arthritis (RA) who have not responded to anti-tumor necrosis factor (TNF) therapy. Response rates and time to relapse vary significantly among treated individuals. The objective of this study was to monitor the response of seropositive and seronegative RA patients to rituximab and correlate relapse with B-cell markers in the two groups.

Methods: Seventeen RA patients (eight seropositive for rheumatoid factor [RF+] and nine seronegative [RF-]) were treated with two cycles of rituximab. After treatment, all patients were re-evaluated at the outpatient clinic, and rituximab was readministered when disease relapse was confirmed by clinical-laboratory measures (Disease Activity Score [DAS]-28). CD20+ cells and CD20 receptor expression levels were estimated at initiation, relapse, and re-evaluation timepoints, and were compared between the two groups.

Results: Seropositive patients responded favorably to treatment compared with the seronegative group. The mean time to relapse was 337.5±127.0 days for the RF+ patients versus 233.3 ± 59.6 days for the RF-patients (p = 0.043), despite more aggressive concomitant treatment in the seronegative group. The DAS28 decrease 3 months after treatment was 1.695 ± 1.076 in seropositive patients versus 0.94±1.62 in seronegative patients. At relapse, CD20 receptor expression (molecules/cell) was higher in RF+ patients than in their RF-counterparts, despite a significantly lower percentage of CD20+ cells.

Conclusion: Rituximab treatment is efficient in both seropositive and seronegative RA. However, seropositive RA patients tend to respond favorably compared with seronegative patients. The differential CD20 receptor expression in the two groups at relapse potentially suggests a different pathogenetic mechanism of relapse and merits further investigation.

Keywords

Rheumatoid Arthritis Patient Clinical Relapse DAS28 Score Seropositive Patient Seronegative Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this review/study.

References

  1. 1.
    Kwan-Morley J, Albert D. B-cell inhibitors as therapy for rheumatoid arthritis: an update. Curr Rheumatol Rep 2007; 9: 401–6PubMedCrossRefGoogle Scholar
  2. 2.
    Looney RJ. B cell-targeted therapy for rheumatoid arthritis: an update on the evidence. Drugs 2006; 66: 625–39PubMedCrossRefGoogle Scholar
  3. 3.
    Cohen SB, Emery P, Greenwald MW, et al., REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006; 54: 2793–806PubMedCrossRefGoogle Scholar
  4. 4.
    Emery P, Fleischmann R, Filipowicz-Sosnowska A, et al., DANCER Study Group. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 2006; 54: 1390–400PubMedCrossRefGoogle Scholar
  5. 5.
    Szodoray P, Alex P, Dandapani V, et al. Apoptotic effect of rituximab on peripheral blood B cells in rheumatoid arthritis. Scand J Immunol 2004; 60: 209–18PubMedCrossRefGoogle Scholar
  6. 6.
    Roll P, Dörner T, Tony HP. Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment. Arthritis Rheum 2008; 58: 1566–75PubMedCrossRefGoogle Scholar
  7. 7.
    Dass S, Rawstron AC, Vital EM, et al. Highly sensitive B cell analysis predicts response to rituximab therapy in rheumatoid arthritis. Arthritis Rheum 2008; 58: 2993–9PubMedCrossRefGoogle Scholar
  8. 8.
    Breedveld F, Agarwal S, Yin M, et al. Rituximab pharmacokinetics in patients with rheumatoid arthritis: B-cell levels do not correlate with clinical response. J Clin Pharmacol 2007; 47: 1119–28PubMedCrossRefGoogle Scholar
  9. 9.
    Taylor RP, Lindorfer MA. Immunotherapeutic mechanisms of anti-CD20 monoclonal antibodies. Curr Opin Immunol 2008; 20: 444–9PubMedCrossRefGoogle Scholar
  10. 10.
    Thurlings RM, Vos K, Gerlag DM, et al. Disease activity-guided rituximab therapy in rheumatoid arthritis: the effects of retreatment in initial non-responders versus initial responders. Arthritis Rheum 2008; 58: 3657–64PubMedCrossRefGoogle Scholar
  11. 11.
    Smolen JS, Aletaha D, Grisar J, et al. The need for prognosticators in rheumatoid arthritis: biological and clinical markers. Where are we now? Arthritis Res Ther 2008; 10:208PubMedCrossRefGoogle Scholar
  12. 12.
    Palanichamy A, Roll P, Theiss R, et al. Modulation of molecular imprints in the antigen-experienced B cell repertoire by rituximab. Arthritis Rheum 2008; 58: 3665–74PubMedCrossRefGoogle Scholar
  13. 13.
    Jiang L, Yuan CM, Hubacheck J, et al. Variable CD52 expression in mature T cell and NK cell malignancies: implications for alemtuzumab therapy. Br J Haematol 2009; 145: 173–9PubMedCrossRefGoogle Scholar
  14. 14.
    Kavanaugh A, Rosengren S, Lee SJ, et al. Assessment of rituximab’s immunomodulatory synovial effects (the ARISE trial): I. Clinical and synovial biomarker results. Ann Rheum Dis 2008; 67: 402–8PubMedCrossRefGoogle Scholar
  15. 15.
    Vos K, Thurlings RM, Wijbrandts CA, et al. Early effects of rituximab on the synovial cell infiltrate in patients with rheumatoid arthritis. Arthritis Rheum 2007; 56: 772–8PubMedCrossRefGoogle Scholar
  16. 16.
    Frampton JE, Scott LJ. Rituximab: in rheumatoid arthritis. Biodrugs 2007;21: 333–41PubMedCrossRefGoogle Scholar
  17. 17.
    Bokarewa M, Lindholm C, Zendjanchi K, et al. Efficacy of anti-CD20 treatment in patients with rheumatoid arthritis resistant to a combination of methotrexate/anti-TNF therapy. Scand J Immunol 2007; 66: 476–83PubMedCrossRefGoogle Scholar
  18. 18.
    Erwards JC, Cambridge G. Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes. Rheumatology (Oxford) 2001; 40: 205–11CrossRefGoogle Scholar
  19. 19.
    Cambridge G, Leandro MJ, Edwards JC, et al. Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum 2003; 48: 2146–54PubMedCrossRefGoogle Scholar
  20. 20.
    Williams ME, Densmore JJ, Pawluczkowycz AW, et al. Thrice-weekly low-dose rituximab decreases CD20 loss via shaving and promotes enhanced targeting in chronic lymphocytic leukaemia. J Immunol 2006; 177: 7435–43PubMedGoogle Scholar
  21. 21.
    Silverman GJ, Boyle DL. Understanding the mechanistic basis in rheumatoid arthritis for clinical response to anti CD20 therapy: the B-cell roadblock hypothesis. Immunol Rev 2008; 223: 175–85PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Athina Pyrpasopoulou
    • 1
  • Stella Douma
    • 1
  • Areti Triantafyllou
    • 1
  • Elisavet Simoulidou
    • 1
  • Magda Samara
    • 2
  • Efthymia Parapanisiou
    • 2
  • Spyros Aslanidis
    • 1
  1. 1.2nd Propedeutic Department of Internal MedicineHippokration General HospitalThessalonikiGreece
  2. 2.Laboratory of ImmunologyHippokration General HospitalThessalonikiGreece

Personalised recommendations