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Potential and prognostic factor for belimumab-free remission in patients with systemic lupus erythematosus: a single-center retrospective analysis

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Abstract

Belimumab is an effective and safe treatment option for systemic lupus erythematosus (SLE). However, data on treatment cessation are lacking. Thus, we investigated belimumab-free remission in SLE patients. SLE patients receiving belimumab in our institute (May 1, 2013–May 31, 2019) were retrospectively identified using electronic health records. Eligibility criteria included receiving belimumab for > 180 days and discontinuation for any reason. BILAG category A or B in at least one organ system indicated a disease flare. Follow-up monitoring during post-treatment at week 52 identified relapse-free and relapse patients. Thirty-one patients received belimumab, and 8 patients were included. Of the 8 patients, 4 relapsed within 52 weeks. At belimumab discontinuation, relapse-free patients achieved lower SELENA-SLEDAI (1 [IQR, 0–2] vs. 7 [IQR, 5.5–8] (p = 0.03)), received significantly less steroid (prednisolone equivalent, 3.0 mg/day [IQR, 2.8–3.2] vs. 9.5 mg/day [IQR, 7.3–13.3], p = 0.02) than relapse patients, and significantly more relapse-free patients achieved SELENA-SLEDAI less than 4 and received prednisolone less than 5 mg/day than relapse patients. Furthermore, on discontinuation day, relapse-free patients tended to have higher C3 (91.0 mg/dL [IQR, 78.8–102.3] vs. 56.0 mg/dL [IQR, 39.8–73.0], p = 0.15) and C4 levels (22.0 mg/dL [IQR, 19.00–26.00] vs. 11.0 mg/dL [IQR, 6.00–16.00], p = 0.08) and less anti-dsDNA antibody (5.2 IU/mL [IQR, 3.8–7.8] vs. 48.0 IU/mL [IQR, 11.5–137.3], p = 0.08) than relapse patients. Belimumab discontinuation can be considered for patients who achieved good responses. Normalization of complement, anti-dsDNA antibody, SELENA-SLEDAI less than 4, and steroid dosage less than 5 mg/day might be prognostic markers for belimumab-free remission.

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References

  1. Hahn BH (2013) Belimumab for systemic lupus erythematosus. N Engl J Med 368:1528–1535. https://doi.org/10.1056/NEJMct1207259

    Article  CAS  PubMed  Google Scholar 

  2. Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, Recta V, Zhong J, Freimuth W (2008) Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum 58:2453–2459. https://doi.org/10.1002/art.23678

    Article  CAS  PubMed  Google Scholar 

  3. Cancro MP, D'Cruz DP, Khamashta MA (2009) The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Invest 119:1066–1073. https://doi.org/10.1172/JCI38010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Burness CB, McCormack PL (2011) Belimumab: in systemic lupus erythematosus. Drugs 71:2435–2444. https://doi.org/10.2165/11208440-000000000-00000

    Article  CAS  PubMed  Google Scholar 

  5. Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D, Sanchez-Guerrero J, Schwarting A, Merrill JT, Chatham WW, Stohl W, Ginzler EM, Hough DR, Zhong ZJ, Freimuth W, van Vollenhoven RF; BLISS-76 Study Group (2011) A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum 63:3918–3930. https://doi.org/10.1002/art.30613

    Article  CAS  Google Scholar 

  6. Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, León MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA; BLISS-52 Study Group (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377:721–731. https://doi.org/10.1016/S0140-6736(10)61354-2

    Article  CAS  Google Scholar 

  7. Zhang F, Bae SC, Bass D, Chu M, Egginton S, Gordon D, Roth DA, Zheng J, Tanaka Y (2018) A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis 77:355–363. https://doi.org/10.1136/annrheumdis-2017-211631

    Article  CAS  PubMed  Google Scholar 

  8. Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D (2017) Efficacy and safety of subcutaneous belimumab in systemic lupus erythematosus: a fifty-two-week randomized, double-blind, placebo-controlled study. Arthritis Rheumatol 69:1016–1027. https://doi.org/10.1002/art.40049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wallace DJ, Ginzler, EM, Merrill JT, Furie RA, Stohl W, Chatham WW, Weinstein A, McKay JD, McCune WJ, Petri M, Fettiplace J, Roth DA, Ji B, Heath A (2019) Safety and efficacy of belimumab plus standard therapy for up to thirteen years in patients with systemic lupus erythematosus. Arthritis Rheumatol 71(7):1125–1134. https://doi.org/10.1002/art.40861

  10. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, Cervera R, Doria A, Gordon C, Govoni M, Houssiau F, Jayne D, Kouloumas M, Kuhn A, Larsen JL, Lerstrøm K, Moroni G, Mosca M, Schneider M, Smolen JS, Svenungsson E, Tesar V, Tincani A, Troldborg A, van Vollenhoven R, Wenzel J, Bertsias G, Boumpas DT (2019) 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 78(6):736–745

    Article  CAS  PubMed  Google Scholar 

  11. Petri M, Magder LS (2018) Comparison of remission and lupus low disease activity state in damage prevention in a United States systemic lupus Erythematosus cohort. Arthritis Rheumatol 70(11):1790–1795

    Article  PubMed  PubMed Central  Google Scholar 

  12. Huscher D, Mittendorf T, von Hinüber U, Kötter I, Hoese G, Pfäfflin A, Bischoff S, Zink A, German Collaborative Arthritis Centres (2015) Evolution of cost structures in rheumatoid arthritis over the past decade. Ann Rheum Dis 74:738–745. https://doi.org/10.1136/annrheumdis-2013-204311

    Article  PubMed  Google Scholar 

  13. Murphy G, Isenberg DA (2019) New therapies for systemic lupus erythematosus - past imperfect, future tense. Nat Rev Rheumatol 15:403–412. https://doi.org/10.1038/s41584-019-0235-5

    Article  PubMed  Google Scholar 

  14. Lee YH, Song GG (2018) Comparative efficacy and safety of intravenous or subcutaneous belimumab in combination with standard therapy in patients with active systemic lupus erythematosus: a Bayesian network meta-analysis of randomized controlled trials. Lupus 27:112–119. https://doi.org/10.1177/0961203317713143

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Immuno-Rheumatology Center, St. Luke’s International Hospital, Tokyo, Japan

    Takehiro Nakai, Sho Fukui, Yukihiko Ikeda, Hisanori Shimizu, Hiromichi Tamaki & Masato Okada

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  1. Takehiro Nakai
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  2. Sho Fukui
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  3. Yukihiko Ikeda
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  4. Hisanori Shimizu
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  5. Hiromichi Tamaki
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  6. Masato Okada
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Correspondence to Takehiro Nakai.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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MO has received speaking fees and/or honoraria from Eli Lilly and Company, Santen Pharmaceutical, Mitsubishi Tanabe Pharma, Pfizer, and Abbott Japan.

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Nakai, T., Fukui, S., Ikeda, Y. et al. Potential and prognostic factor for belimumab-free remission in patients with systemic lupus erythematosus: a single-center retrospective analysis. Clin Rheumatol 39, 3653–3659 (2020). https://doi.org/10.1007/s10067-020-05052-0

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  • DOI: https://doi.org/10.1007/s10067-020-05052-0

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