Advertisement

Promising Treatment Alternatives

  • Taku Yoshio
  • Hiroshi Okamoto
Chapter

Abstract

The current therapeutic approach to the difficult manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE) remains empirical and is based on clinical experience. Available data on the use of rituximab in refractory NPSLE come from a large number of case reports and some open-label studies. Two patients with persistently active NPSLE, despite conventional therapy, responded dramatically to rituximab are described in this chapter. Current evidence on the therapeutic use of rituximab in this chapter is also analyzed through the English-language literatures. Evidence for the effectiveness of rituximab as induction therapy in NPSLE is based solely on several case reports and non-controlled trials. Although it is not yet possible to make definite recommendations, the global analysis of these cases supports the off-label use of rituximab in cases of severe refractory NPSLE. Furthermore, we present the blockade of new targets which may impact the future treatment of NPSLE.

Keywords

NPSLE Anti-CD20 antibodies Rituximab Anti-CD22 antibodies Epratuzumab Anti-BLyS antibodies Belimumab Tabalumab Blisibimod BLyS and april receptor Atacicept Anti-IL-6 receptor antibodies Tocilizumab Anti-IFN-α antibodies Sifalimumab Rontalizumab Anti-terminal complement components C5a and C5b-9 antibodies Eculizumab 

References

  1. 1.
    Unterman A, et al. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum. 2011;41:1–11.CrossRefPubMedGoogle Scholar
  2. 2.
    Bertsias GK, Boumpas DT. Pathogenesis diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol. 2010;6:358–67.CrossRefPubMedGoogle Scholar
  3. 3.
    Sanna G, et al. Neuropsychiatric involvement in systemic lupus erythematosus: current therapeutic approach. Curr Pharm Des. 2008;14:1261–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Tieng AT, Peeva E. B- cell-directed therapies in systemic lupus erythematosus. Semin Arthritis Rheum. 2008;38:218–27.CrossRefPubMedGoogle Scholar
  5. 5.
    Ramos Casals M, et al. Rituximab in systemic lupus erythematosus. A systematic review of off-label use in 188 cases. Lupus. 2009;18:767–76.CrossRefPubMedGoogle Scholar
  6. 6.
    Murray E, Perry M. Off-label use of riyuximab in systemic lupus erythematosus: a systematic review. Clin Rheumatol. 2010;29:707–16.CrossRefPubMedGoogle Scholar
  7. 7.
    Glennie MJ, et al. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol. 2007;44:3823–37.CrossRefPubMedGoogle Scholar
  8. 8.
    Merrill JT, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 2010;62:222–33.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Rovin BH, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the lupus nephritis assessment with rituximab study. Arthritis Rheum. 2012;64:1215–26.CrossRefPubMedGoogle Scholar
  10. 10.
    Cobo-Ibanez T, et al. Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review. Semin Arthritis Rheum. 2014;44:175–85.CrossRefPubMedGoogle Scholar
  11. 11.
    Weide R, et al. Successful longterm treatment of systemic lupus erythematosus with rituximab maintenance therapy. Lupus. 2003;12:779–82.CrossRefPubMedGoogle Scholar
  12. 12.
    Gottenberg JE, et al. Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis. 2005;64:913–20.CrossRefPubMedGoogle Scholar
  13. 13.
    Leandro MJ, et al. B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients. Rheumatology. 2005;44:1542–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Armstrong DJ, et al. SLE-associated transverse myelitis successfully treated with rituximab (anti-CD20 monoclonal antibody). Rheumatol Int. 2006;26:771–2.CrossRefPubMedGoogle Scholar
  15. 15.
    Birnbaum J, Kerr D. Optic neuritis and recurrent myelitis in a woman with systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2008;4:381–6.PubMedGoogle Scholar
  16. 16.
    Abud-Mendoza C, et al. Treating severe systemic lupus erythematosus with rituximab. An open study. Reumatol Clin. 2009;5:147–52.CrossRefPubMedGoogle Scholar
  17. 17.
    Lu TY, et al. A retrospective seven-year analysis of the use of B cell depletion therapy in systemic lupus erythematosus at university college London hospital: the first fifty patients. Arthritis Rheum. 2009;61:482–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Nasir S, et al. Nineteen episodes of recurrent myelitis in a woman with neuromyelitis optica and systemic lupus erythematosus. Arch Neurol. 2009;66:1160–3.CrossRefPubMedGoogle Scholar
  19. 19.
    Espinosa G, et al. Transverse myelitis affecting more than 4 spinal segments associated with systemic lupus erythematosus: clinical, immunological, and radiological characteristics of 22 patients. Semin Arthritis Rheum. 2010;39:246–56.CrossRefPubMedGoogle Scholar
  20. 20.
    Narvaez J, et al. Rituximab therapy in refractory neuropsychiatric lupus: current clinical evidence. Semin Arthritis Rheum. 2011;41:364–72.CrossRefPubMedGoogle Scholar
  21. 21.
    Pinto LF, et al. Rituximab induces a rapid and sustained remission in Colombian patients with severe and refractory systemic lupus erythematosus. Lupus. 2011;20:1219–26.CrossRefPubMedGoogle Scholar
  22. 22.
    Ye Y, et al. Rituximab in the treatment of severe lupus myelopathy. Clin Rheumatol. 2011;30:981–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Saito K, et al. Successful treatment with anti-CD20 monoclonal antibody (rituximab) of life-threatening refractory systemic lupus erythematosus with renal and central nervous system involvement. Lupus. 2003;12:798–800.CrossRefPubMedGoogle Scholar
  24. 24.
    Tokunaga M, et al. Down-regulation of CD40 and CD80 on B cells in patients with life-threatening systemic lupus erythematosus after successful treatment with rituximab. Rheumatology. 2005;44:176–82.CrossRefPubMedGoogle Scholar
  25. 25.
    Tokunaga M, et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis. 2007;66:470–5.CrossRefPubMedGoogle Scholar
  26. 26.
    Tanaka Y, et al. A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus. Mod Rheumatol. 2007;17:191–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Dale RC, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology. 2014;83:142–50.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Sfikakis PP, et al. Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum. 2005;52:501–13.CrossRefPubMedGoogle Scholar
  29. 29.
    Anolik JH, et al. Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum. 2004;50:3580–90.CrossRefPubMedGoogle Scholar
  30. 30.
    Driver CB, et al. The B cell in systemic lupus erythaematosus: a rational target for more effective therapy. Ann Rheum Dis. 2008;67:1374–81.CrossRefPubMedGoogle Scholar
  31. 31.
    Harvey PR, Gordon C. B- cell targeted therapies in systemic lupus erythematosus: successes and challenges. BioDrugs. 2013;27:85–95.CrossRefPubMedGoogle Scholar
  32. 32.
    Study of epratuzumab versus placebo in subjects with moderate to severe general systemic lupus erythematosus (SLE) (EMBODY 2). Available at: https://clinicaltrials.gov/ct2/show/ NCT01261793. Accessed 22 Nov 2015.
  33. 33.
    George-Chandy A, et al. Raised intrathecal levels of APRIL and BAFF in patients with systemic lupus erythematosus: relationship to neuropsychiatric symptoms. Arthritis Res Ther. 2008;10:R97.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Hopia L, et al. Cerebrospinal fluid levels of a proliferation-inducing ligand (APRIL) are increased in patients with neuropsychiatric systemic lupus erythematosus. Scand J Rheumatol. 2011;40:363–72.CrossRefPubMedGoogle Scholar
  35. 35.
    Manzi S, et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis. 2012;71:1833–8.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ding HJ, Gordon C. New biologic therapy for systemic lupus erythematosus. Curr Opin Pharmacol. 2013;13:405–12.CrossRefPubMedGoogle Scholar
  37. 37.
    Yoshio T, et al. IL-6, IL-8, IP-10, MCP-1 and C-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus. Lupus. 2016;25:997–1003.CrossRefPubMedGoogle Scholar
  38. 38.
    Fragoso-Loyo H, et al. Interleukin-6 and chemokines in the neuropsychiatric manifestations of systemic lupus erythematosus. Arthritis Rheum. 2007;56:1242–50.CrossRefPubMedGoogle Scholar
  39. 39.
    Svenungsson E, et al. Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus. Ann Rheum Dis. 2001;60:372–9.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Trysberg E, et al. Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus. 2000;9:498–503.CrossRefPubMedGoogle Scholar
  41. 41.
    Dafny N, Yang PB. Interferon and the central nervous system. Eur J Pharmacol. 2005;523:1–15.CrossRefPubMedGoogle Scholar
  42. 42.
    Fragoso-Loyo H, et al. Utility of interferon-alpha as a biomarker in central neuropsychiatric involvement in systemic lupus erythematosus. J Rheumatol. 2012;39:504–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Santer DM, et al. Potent induction of IFN-alpha and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus. J Immunol. 2009;182:1192–201.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Illei GG, et al. Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum. 2010;62:542–52.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Pardridge WM. Targeted delivery of protein and gene medicines through the blood-brain barrier. Clin Pharmacol Ther. 2015;97:347–61.CrossRefPubMedGoogle Scholar
  46. 46.
    Mathian A, et al. Targeting interferons in systemic lupus erythematosus: current and future prospects. Drugs. 2015;75:835–46.CrossRefPubMedGoogle Scholar
  47. 47.
    Jacob A, et al. C5a alters blood-brain barrier integrity in experimental lupus. FASEB J. 2010;24:1682–8.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Jacob A, et al. Inhibition of C5a receptor alleviates experimental CNS lupus. J Neuroimmunol. 2010;221:46–52.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Alexander JJ, et al. Administration of the soluble complement inhibitor, Crry-Ig, reduces inflammation and aquaporin 4 expression in lupus cerebritis. Biochim Biophys Acta. 2003;1639:169–76.CrossRefPubMedGoogle Scholar
  50. 50.
    Cavazzana I, et al. Complement activation in anti-phospholipid syndrome: a clue for an inflammatory process? J Autoimmun. 2007;28:160–4.CrossRefPubMedGoogle Scholar
  51. 51.
    Thurman JM, et al. A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice. Mol Immunol. 2005;42:87–97.CrossRefPubMedGoogle Scholar
  52. 52.
    Barilla-Labarca ML, et al. Targeting the complement system in systemic lupus erythematosus and other diseases. Clin Immunol. 2013;148:313–21.CrossRefPubMedGoogle Scholar
  53. 53.
    Diamond B, et al. Losing your nerves? Maybe it’s the antibodies. Nat Rev Immunol. 2009;9:449–56.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Rheumatology and Clinical ImmunologySchool of Medicine, Jichi Medical UniversityShimotsuke-shiJapan
  2. 2.Minami-otsuka institute of technologyMinami-otsuka ClinicTokyoJapan

Personalised recommendations