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Six-month outcomes of infliximab and tocilizumab therapy in non-infectious retinal vasculitis

Abstract

Purpose

To evaluate the efficacy of infliximab (IFX, 5–10 mg/kg) (Group 1) and tocilizumab (TCZ, 4–8 mg/kg) (Group 2) infusions in non-infectious retinal vasculitis (RV) using Angiographic Scoring for the Uveitis Working Group fluorescein angiography (FA) scoring system.

Methods

Records of 14 patients (24 eyes) in Group 1 and 8 patients (11 eyes) in Group 2 were retrospectively evaluated to assess visual acuity (VA), anterior chamber cell and flare, vitreous haze, central subfield thickness (CST), and FA scoring at baseline and 6 months of follow-up. The measurements were employed to grade in each group.

Results

In Group 1 and 2, respectively, there was no underlying disease in 9 (60%) and 3 (42.9%) patients. Three (42.9%) patients in Group 2 had juvenile idiopathic arthritis (JIA) as the most common identified cause. Mean improvement in VA (log MAR) and CST were 0.04 ± 0.14 and 40.3 ± 78.5 µm in Group 1; 0.04 ± 0.09 and 47.3 ± 82.3 µm in Group 2, respectively. Mean FA scores were significantly reduced from 12.4 ± 5.2 and 11.6 ± 4.4 at baseline to 6.4 ± 5.0 and 5.8 ± 3.9 at 6-month in Group 1 and 2, respectively. In Group 2, 9 eyes of 6 patients (75%) had the history of IFX use prior to TCZ initiation. There was no significant safety concern requiring treatment discontinuation during the follow-up in either group.

Conclusion

IFX and TCZ infusions showed statistically significant improvement of non-infectious RV as shown by ASUWOG FA Scoring System. TCZ, as well as IFX, appeared to be effective treatment options for non-infectious RV.

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Fig. 1: Fluorescein angiography images of a representative patient who received infliximab at baseline.
Fig. 2: Fluorescein angiography images of a representative patient who received tocilizumab at baseline.

Data availability

The datasets generated during and/or analyzed during the current study are only available from the corresponding author on reasonable request.

References

  1. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of Uveitis Nomenclature Working G. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005;140:509–16. https://doi.org/10.1016/j.ajo.2005.03.057.

    Article  PubMed  Google Scholar 

  2. Abu El-Asrar AM, Herbort CP, Tabbara KF. Retinal vasculitis. Ocul Immunol Inflamm. 2005;13:415–33. https://doi.org/10.1080/09273940591003828.

    Article  PubMed  Google Scholar 

  3. El-Asrar AM, Herbort CP, Tabbara KF. A clinical approach to the diagnosis of retinal vasculitis. Int Ophthalmol. 2010;30:149–73. https://doi.org/10.1007/s10792-009-9301-3.

    Article  PubMed  Google Scholar 

  4. Ciardella AP, Prall FR, Borodoker N, Cunningham ET Jr. Imaging techniques for posterior uveitis. Curr Opin Ophthalmol. 2004;15:519–30. https://doi.org/10.1097/01.icu.0000144386.05116.c5.

    Article  PubMed  Google Scholar 

  5. Tugal-Tutkun I, Herbort CP, Khairallah M, Angiography Scoring for Uveitis Working G. Scoring of dual fluorescein and ICG inflammatory angiographic signs for the grading of posterior segment inflammation (dual fluorescein and ICG angiographic scoring system for uveitis). Int Ophthalmol. 2010;30:539–52. https://doi.org/10.1007/s10792-008-9263-x.

    Article  PubMed  Google Scholar 

  6. Suhler EB. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol. 2005;123:903–12. https://doi.org/10.1001/archopht.123.7.903.

    Article  CAS  PubMed  Google Scholar 

  7. Kang HM, Lee SC. Long-term progression of retinal vasculitis in Behcet patients using a fluorescein angiography scoring system. Graefes Arch Clin Exp Ophthalmol. 2014;252:1001–8. https://doi.org/10.1007/s00417-014-2637-z.

    Article  PubMed  Google Scholar 

  8. Balci O, Jeannin B, Herbort CP Jr. Contribution of dual fluorescein and indocyanine green angiography to the appraisal of posterior involvement in birdshot retinochoroiditis and Vogt-Koyanagi-Harada disease. Int Ophthalmol. 2018;38:527–39. https://doi.org/10.1007/s10792-017-0487-5.

    Article  PubMed  Google Scholar 

  9. Sadiq MA, Hassan M, Afridi R, Halim MS, Do DV, Sepah YJ, et al. Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study. Int J Retin Vitreous. 2020;6:47. https://doi.org/10.1186/s40942-020-00245-w

    Article  Google Scholar 

  10. Hatemi G, Silman A, Bang D, Bodaghi B, Chamberlain AM, Gul A, et al. EULAR recommendations for the management of Behcet disease. Ann Rheum Dis. 2008;67:1656–62. https://doi.org/10.1136/ard.2007.080432.

    Article  CAS  PubMed  Google Scholar 

  11. Rosenbaum JT, Sibley CH, Lin P. Retinal vasculitis. Curr Opin Rheumatol. 2016;28:228–35. https://doi.org/10.1097/BOR.0000000000000271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Calvo-Río V, Blanco R, Beltrán E, Sánchez-Bursón J, Mesquida M, Adán A, et al. Anti-TNF-alpha therapy in patients with refractory uveitis due to Behcet’s disease: a 1-year follow-up study of 124 patients. Rheumatol (Oxf). 2014;53:2223–31. https://doi.org/10.1093/rheumatology/keu266.

    Article  Google Scholar 

  13. Sharma PK, Markov GT, Bajwa A, Foster CS. Long-Term Efficacy of Systemic Infliximab in Recalcitrant Retinal Vasculitis. Retina. 2015;35:2641–6. https://doi.org/10.1097/IAE.0000000000000624.

    Article  CAS  PubMed  Google Scholar 

  14. Eser Ozturk H, Oray M, Tugal-Tutkun I. Tocilizumab for the Treatment of Behcet Uveitis that Failed Interferon Alpha and Anti-Tumor Necrosis Factor-Alpha Therapy. Ocul Immunol Inflamm. 2018;26:1005–14. https://doi.org/10.1080/09273948.2017.1355471

    Article  CAS  PubMed  Google Scholar 

  15. Atienza-Mateo B, Calvo-Rio V, Beltran E, Martinez-Costa L, Valls-Pascual E, Hernandez-Garfella M, et al. Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behcet’s disease: multicentre retrospective study. Rheumatol (Oxf). 2018;57:856–64. https://doi.org/10.1093/rheumatology/kex480.

    Article  CAS  Google Scholar 

  16. Fabiani C, Sota J, Rigante D, Vitale A, Emmi G, Lopalco G, et al. Efficacy of adalimumab and infliximab in recalcitrant retinal vasculitis inadequately responsive to other immunomodulatory therapies. Clin Rheumatol. 2018;37:2805–9. https://doi.org/10.1007/s10067-018-4133-z.

    Article  PubMed  Google Scholar 

  17. Calvo-Río V, Santos-Gómez M, Calvo I, González-Fernández MI, López-Montesinos B, Mesquida M, et al. Anti-Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to Anti-Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty-Five Patients. Arthritis Rheumatol. 2017;69:668–75. https://doi.org/10.1002/art.39940.

    Article  CAS  PubMed  Google Scholar 

  18. Muselier A, Bielefeld P, Bidot S, Vinit J, Besancenot JF, Bron A. Efficacy of tocilizumab in two patients with anti-TNF-alpha refractory uveitis. Ocul Immunol Inflamm. 2011;19:382–3. https://doi.org/10.3109/09273948.2011.606593.

    Article  CAS  PubMed  Google Scholar 

  19. Wennink RAW, Ayuso VK, de Vries LA, Vastert SJ, de Boer JH. Tocilizumab as an Effective Treatment Option in Children with Refractory Intermediate and Panuveitis. Ocul Immunol Inflamm. 2021;29:21–25. https://doi.org/10.1080/09273948.2020.1712431.

    Article  CAS  PubMed  Google Scholar 

  20. Ucan Gunduz G, Yalcinbayir O, Cekic S, Yildiz M, Kilic SS. Anti-Tumor Necrosis Factor Treatment in the Management of Pediatric Noninfectious Uveitis: Infliximab Versus Adalimumab. J Ocul Pharm Ther. 2021;37:236–40. https://doi.org/10.1089/jop.2020.0081.

    Article  CAS  Google Scholar 

  21. Santos-Gómez M, Calvo-Río V, Blanco R, Beltrán E, Mesquida M, Adán A, et al. The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behcet’s disease: results of a multicentre open-label study. Clin Exp Rheumatol 2016;34:S34–S40.

    PubMed  Google Scholar 

  22. Ashkenazy N, Saboo US, Abraham A, Ronconi C, Cao JH. Successful treatment with infliximab after adalimumab failure in pediatric noninfectious uveitis. J AAPOS. 2019;23:151 e1–151 e5. https://doi.org/10.1016/j.jaapos.2019.02.006.

    Article  PubMed  Google Scholar 

  23. Maleki A, Garcia CM, Asgari S, Manhapra A, Foster CS Response to the Second TNF-alpha Inhibitor (Adalimumab or Infliximab) after Failing the First One in Refractory Idiopathic Inflammatory Retinal Vascular Leakage. Ocul Immunol Inflamm. 2021:1-10. https://doi.org/10.1080/09273948.2020.1869787.

  24. Sepah YJ, Sadiq MA, Chu DS, Dacey M, Gallemore R, Dayani P, et al. Primary (Month-6) Outcomes of the STOP-Uveitis Study: Evaluating the Safety, Tolerability, and Efficacy of Tocilizumab in Patients With Noninfectious Uveitis. Am J Ophthalmol. 2017;183:71–80. https://doi.org/10.1016/j.ajo.2017.08.019.

    Article  CAS  PubMed  Google Scholar 

  25. Maleki A, Manhapra A, Asgari S, Chang PY, Foster CS, Anesi SD. Tocilizumab Employment in the Treatment of Resistant Juvenile Idiopathic Arthritis Associated Uveitis. Ocul Immunol Inflamm. 2021;29:14–20. https://doi.org/10.1080/09273948.2020.1817501.

    Article  CAS  PubMed  Google Scholar 

  26. Farhat R, Clavel G, Villeneuve D, Abdelmassih Y, Sahyoun M, Gabison E, et al. Sustained Remission with Tocilizumab in Refractory Relapsing Polychondritis with Ocular Involvement: A Case Series. Ocul Immunol Inflamm. 2021;29:9–13. https://doi.org/10.1080/09273948.2020.1763405.

    Article  CAS  PubMed  Google Scholar 

  27. Adán A, Mesquida M, Llorenç V, Espinosa G, Molins B, Hernández MV, et al. Tocilizumab treatment for refractory uveitis-related cystoid macular edema. Graefes Arch Clin Exp Ophthalmol. 2013;251:2627–32. https://doi.org/10.1007/s00417-013-2436-y.

    Article  CAS  PubMed  Google Scholar 

  28. Vegas-Revenga N, Calvo-Rio V, Mesquida M, Adan A, Hernandez MV, Beltran E, et al. Anti-IL6-Receptor Tocilizumab in Refractory and Noninfectious Uveitic Cystoid Macular Edema: Multicenter Study of 25 Patients. Am J Ophthalmol. 2019;200:85–94. https://doi.org/10.1016/j.ajo.2018.12.019.

    Article  CAS  PubMed  Google Scholar 

  29. Paul S, Zhang X. Small sample GEE estimation of regression parameters for longitudinal data. Stat Med. 2014;33:3869–81. https://doi.org/10.1002/sim.6198.

    Article  PubMed  Google Scholar 

  30. Mesquida M, Molins B, Llorenc V, Sainz de la Maza M, Adan A. Long-term effects of tocilizumab therapy for refractory uveitis-related macular edema. Ophthalmology. 2014;121:2380–6. https://doi.org/10.1016/j.ophtha.2014.06.050.

    Article  PubMed  Google Scholar 

  31. Haraoui B, Cameron L, Ouellet M, White B. Anti-infliximab antibodies in patients with rheumatoid arthritis who require higher doses of infliximab to achieve or maintain a clinical response. J Rheumatol. 2006;33:31–6.

    CAS  PubMed  Google Scholar 

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Acknowledgements

IK was supported by a grant from the International Council of Ophthalmology (ICO) Retina Research Foundation (RRF) Helmerich Fellowship Program, as the recipient of 2020 ICO-RRF Helmerich One-Year Fellowship Award. WM was supported by a grant from the Japan Eye Bank Association Oversea Research Program and Kobe University Long Term Oversea Visit Program for Young Researchers.

Funding

Research to Prevent Blindness Department Challenge Award and National Eye Institute of the National Institutes of Health P30 Award (EY026877) have been awarded to the Byers Eye Institute at Stanford University.

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Contributions

IK was responsible for conducting the research, designing the study, extracting and analyzing the data, interpreting the results, writing and revising the manuscript; GU contributed in extracting the data, editing and critical revision of the manuscript; WM was responsible for analyzing the data, interpreting the results, critical revision of the manuscript; JR was responsible for editing and revision of the manuscript; CO contributed in interpreting the data and critical revision of the manuscript; AM contributed in interpreting the data; MSH contributed to design of the study and data interpretation; MZ contributed in analyzing and interpreting the data; SL was responsible for extracting the data; AD was responsible for extracting the data; HG contributed in analyzing and interpreting the data, editing and critical revision of the manuscript; QDN was responsible for critical revision of the manuscript.

Corresponding author

Correspondence to Quan Dong Nguyen.

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QDN serves on the Scientific Advisory Board for Affibody, Acelyrin, and Regeneron. The remaining authors declare that there are no conflicts of interest related to this manuscript.

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Karaca, I., Uludag, G., Matsumiya, W. et al. Six-month outcomes of infliximab and tocilizumab therapy in non-infectious retinal vasculitis. Eye (2022). https://doi.org/10.1038/s41433-022-02315-9

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