Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of efficacy of infliximab for retinal vasculitis and extraocular symptoms in Behçet disease

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

We evaluated ocular symptoms and activity of retinal vasculitis of Behçet disease before and after infliximab therapy, using Behçet disease ocular attack score 24 (BOS24) and fluorescein angiography (FA) score. We also analyzed the efficacy of infliximab for ocular and extraocular symptoms.

Study design

Retrospective study.

Subject and methods

Using medical records, we analyzed FA and BOS24 to evaluate the association between the efficacy of infliximab therapy and FA as well as BOS24 scores. Further, we evaluated the association between FA scores and extraocular symptoms.

Results

After 2 years of infliximab therapy, 6-month BOS24 was significantly reduced compared to that before treatment (PreBOS24-6M). After 4 years of infliximab therapy, 6-month BOS24 was also significantly reduced compared to preBOS24-6M. After 2 years of infliximab therapy, FA score median (interquartile range) decreased significantly compared to that before treatment [FA-2Y vs. preFA: 0 (0-0) vs.15.5 (12-24); P < 0.0001; n = 38]. The FA-4Y score in subjects followed for at least 4 years was also significantly lower than the preFA score [0 (0-0) vs.16.5 (12-24.5); P < 0.0001; n = 28]. Among 38 patients, extraocular symptoms were resolved following treatment in 29 cases (76.3%). No significant correlation was observed between the improvement in FA-2Y and FA-4Y scores and the occurrence and persistence of extraocular symptoms (P = 0.33; n = 38 or P = 0.4; n = 28).

Conclusion

Infliximab therapy is effective for the treatment of ocular and extraocular involvement of Behçet disease. BOS24 and FA scores are useful for evaluating the efficacy of infliximab therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

DAS 28:

Disease activity score in rheumatoid arthritis

BOS24:

Behçet disease ocular attack score 24

FA:

Fluorescein angiography

References

  1. Okada AA, Goto H, Ohno S, Mochizuki M. Multicenter study of infliximab for refractory uveoretinitis in Behçet disease. Arch Ophthalmol. 2012;130:592–8.

    Article  CAS  PubMed  Google Scholar 

  2. Takeuchi M, Kezuka T, Sugita S, Keino H, Namba K, Kaburaki T, et al. Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behçet’s disease: a multicenter study. Ophthalmology. 2014;121:1877–84.

    Article  PubMed  Google Scholar 

  3. Vallet H, Riviere S, Sanna A, Deroux A, Moulis G, Addimanda O, et al. Efficacy of anti-TNF alpha in severe and/or refractory Behçet’s disease: multicenter study of 124 patients. J Autoimmun. 2015;62:67–74.

    Article  CAS  PubMed  Google Scholar 

  4. Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder RN. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2014;121(786–96):e3.

    Google Scholar 

  5. Bendtzen K, Geborek P, Svenson M, Larsson L, Kapetanovic MC, Saxne T. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheumatol. 2006;54:3782–9.

    Article  CAS  Google Scholar 

  6. Sugita S, Yamada Y, Mochizuki M. Relationship between serum infliximab levels and acute uveitis attacks in patients with Behçet disease. Br J Ophthalmol. 2011;95:549–52.

    Article  PubMed  Google Scholar 

  7. Iwata D, Namba K, Mizuuchi K, Kitaichi N, Kase S, Takemoto Y, et al. Correlation between elevation of serum antinuclear antibody titer and decreased therapeutic efficacy in the treatment of Behçet’s disease with infliximab. Graefes Arch Clin Exp Ophthalmol. 2012;250:1081–7.

    Article  CAS  PubMed  Google Scholar 

  8. Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheumatol. 1995;38:44–8.

    Article  CAS  Google Scholar 

  9. Kaburaki T, Namba K, Sonoda K, Kezuka T, Keino H, Fukuhara T, et al. Behçet’s disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab. Jpn J Ophthalmol. 2014;58:120–30.

    Article  CAS  PubMed  Google Scholar 

  10. Deuter CM, Kotter I, Wallace GR, Murray PI, Stubiger N, Zierhut M. Behçet’s disease: ocular effects and treatment. Prog Retin Eye Res. 2008;27:111–36.

    Article  CAS  PubMed  Google Scholar 

  11. Evereklioglu C. Current concepts in the etiology and treatment of Behçet disease. Surv Ophthalmol. 2005;50:297–350.

    Article  PubMed  Google Scholar 

  12. Ozdal PC, Ortac S, Taskintuna I, Firat E. Posterior segment involvement in ocular Behçet’s disease. Eur J Ophthalmol. 2002;12:424–31.

    Article  CAS  PubMed  Google Scholar 

  13. Takeuchi M, Hokama H, Tsukahara R, Kezuka T, Goto H, Sakai J, et al. Risk and prognostic factors of poor visual outcome in Behçet’s disease with ocular involvement Graefes. Arch Clin Exp Ophthalmol. 2005;243:1147–52.

    Article  Google Scholar 

  14. No author listed. Criteria for diagnosis of Behcet’s disease. International Study Group for Behcet’s Disease. Lancet. 1990;335:1078–80.

    Google Scholar 

  15. Kim M, Kwon HJ, Choi EY, Kim SS, Koh HJ, Lee SC. Correlation between fluorescein angiographic findings and visual acuity in Behçet retinal vasculitis. Yonsei Med J. 2015;56:1087–96.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kang HM, Lee SC. Long-term progression of retinal vasculitis in Behçet patients using a fluorescein angiography scoring system. Graefes Arch Clin Exp Ophthalmol. 2014;252:1001–8.

    Article  PubMed  Google Scholar 

  17. Mesquida M, Molins B, Llorenc V, Hernandez MV, Espinosa G, Dick AD, et al. Current and future treatments for Behçet’s uveitis: road to remission. Int Ophthalmol. 2014;34:365–81.

    Article  PubMed  Google Scholar 

  18. Atmaca LS, Sonmez PA. Fluorescein and indocyanine green angiography findings in Behçet’s disease. Br J Ophthalmol. 2003;87:1466–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gedik S, Akova Y, Yilmaz G, Bozbeyoglu S. Indocyanine green and fundus fluorescein angiographic findings in patients with active ocular Behçet’s disease. Ocul Immunol Inflamm. 2005;13:51–8.

    Article  PubMed  Google Scholar 

  20. Keino H, Okada AA, Watanabe T, Taki W. Long-term efficacy of infliximab on background vascular leakage in patients with Behçet’s disease. Eye (Lond). 2014;28:1100–6.

    Article  CAS  Google Scholar 

  21. Baneros-Rojas P, Berrozpe-Villabona C, Peraza-Nieves JE, Diaz-Valle D. Early treatment with infliximab in bilateral occlusive vasculitis as a presenting manifestation of Behçet’ disease. Arch Soc Esp Oftalmol. 2015;90:285–8.

    Article  CAS  PubMed  Google Scholar 

  22. Spitznas M. Understanding Fluorescein Angiography. Berlin: Springer; 2006. p. 73–99.

    Google Scholar 

  23. Nussenblatt R. Uveitis: Fundamentals and Clinical Practice. 4th ed. Philadelphia: Elsevier; 2010. p. 42–71.

    Google Scholar 

  24. Baneros-Rojas P, Berrozpe-Villabona C, Peraza-Nieves JE, Diaz-Valle D. Early treatment with infliximab in bilateral occlusive vasculitis as a presenting manifestation of Behçet’ disease. Arch Soc Esp Oftalmol. 2015;90:285–8.

    Article  CAS  PubMed  Google Scholar 

  25. De Bandt M, Sibilia J, Le Loet X, Prouzeau S, Fautrel B, Marcelli C, et al. Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: a French national survey. Arthritis Res Ther. 2005;7:R545–51.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Teixeira MZ. Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude. Homeopathy. 2016;105:344–55.

    Article  PubMed  Google Scholar 

  27. van der Maas A, Kievit W, van den Bemt BJ, van den Hoogen FH, van Riel PL, den Broeder AA. Down-titration and discontinuation of infliximab in rheumatoid arthritis patients with stable low disease activity and stable treatment: an observational cohort study. Ann Rheum Dis. 2012;71:1849–54.

    Article  PubMed  Google Scholar 

  28. Klarenbeek NB, van der Kooij SM, Guler-Yuksel M, van Groenendael JH, Han KH, Kerstens PJ, et al. Discontinuing treatment in patients with rheumatoid arthritis in sustained clinical remission: exploratory analyses from the BeSt study. Ann Rheum Dis. 2011;70:315–9.

    Article  CAS  PubMed  Google Scholar 

  29. Molander P, Farkkila M, Salminen K, Kemppainen H, Blomster T, Koskela R, et al. Outcome after discontinuation of TNFalpha-blocking therapy in patients with inflammatory bowel disease in deep remission. Inflamm Bowel Dis. 2014;20:1021–8.

    PubMed  Google Scholar 

  30. Tanaka Y, Hirata S. Is it possible to withdraw biologics from therapy in rheumatoid arthritis. Clin Ther. 2013;38:2028–35.

    Article  Google Scholar 

  31. Kim WB, Marinas JE, Qiang J, Shahbaz A, Greaves S, Yeung J. Adverse events resulting in withdrawal of biologic therapy for psoriasis in real-world clinical practice: a Canadian multicenter retrospective study. J Am Acad Dermatol. 2015;73:237–41.

    Article  PubMed  Google Scholar 

  32. Nakashita T, Ando K, Kaneko N, Takahashi K, Motojima S. Potential risk of TNF inhibitors on the progression of interstitial lung disease in patients with rheumatoid arthritis. BMJ Open. 2014;4:e005615.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hansen RA, Gartlehner G, Powell GE, Sandler RS. Serious adverse events with infliximab: analysis of spontaneously reported adverse events. Clin Gastroenterol Hepatol. 2007;5:729–35.

    Article  PubMed  Google Scholar 

  34. Kawaguchi T, Kawazoe Y, Kamoi K, Miyanaga M, Takase H, Sugita S, et al. Clinical course of patients with Behçet’s uveitis following discontinuation of infliximab therapy. Jpn J Ophthalmol. 2014;58:75–80.

    Article  CAS  PubMed  Google Scholar 

  35. Al Rashidi S, Al Fawaz A, Kangave D, Abu El-Asrar AM. Long-term clinical outcomes in patients with refractory uveitis associated with Behçet disease treated with infliximab. Ocul Immunol Inflamm. 2013;21:468–74.

    Article  CAS  PubMed  Google Scholar 

  36. Adan A, Hernandez V, Ortiz S, Molina JJ, Pelegrin L, Espinosa G, et al. Effects of infliximab in the treatment of refractory posterior uveitis of Behçet’s disease after withdrawal of infusions. Int Ophthalmol. 2010;30:577–81.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Ms. Teresa Nakatani for critical revision of the manuscript.

This research is supported by the Ministry of Health and Labour Sciences Research Grants of Japan for Research on Rare and Intractable Diseases.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Akihiko Umazume, Takeshi Kezuka, Yoshihiko Usui, Jun Suzuki & Hiroshi Goto

Authors
  1. Akihiko Umazume
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takeshi Kezuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshihiko Usui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroshi Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takeshi Kezuka.

Ethics declarations

Conflicts of interest

A. Umazume, None; T. Kezuka, Grant (Mitsubishi Tanabe Pharma), Lecture fee (Mitsubishi Tanabe Pharma); Y. Usui, None; J. Suzuki, None; H. Goto, Grant (Mitsubishi Tanabe Pharma), Lecture fee (Mitsubishi Tanabe Pharma).

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Umazume, A., Kezuka, T., Usui, Y. et al. Evaluation of efficacy of infliximab for retinal vasculitis and extraocular symptoms in Behçet disease. Jpn J Ophthalmol 62, 390–397 (2018). https://doi.org/10.1007/s10384-018-0589-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-018-0589-2

Keywords

Search

Navigation