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Rituximab in systemic lupus erythematosus and lupus nephritis.

Abstract

Treatment options for systemic lupus erythematosus (SLE) and lupus nephritis (LN) have high associated morbidity and mortality. Side effects, particularly from long-term corticosteroid usage, limit patient adherence, with subsequent impacts on treatment efficacy. In addition, a subset of patients with SLE/LN fails to respond to current standard immunotherapy. There is an urgent need to develop steroid-sparing treatment regimens as well as novel therapies for the management of refractory disease. Rituximab is a chimeric mouse/human monoclonal antibody directed against the B cell CD20 receptor. It has been used in the treatment of non-Hodgkin's lymphoma for over 30 years and has an excellent safety profile. Recent work has demonstrated a role for B cell depletion therapy in the management of autoimmune disease, and the efficacy of rituximab in many observational studies in SLE and LN has been noted. Unfortunately, two large randomised controlled trials evaluating rituximab for the treatment of renal and non-renal lupus failed to meet their primary endpoints. Reasons for this have been discussed extensively within the medical community with a general consensus that trial design (steroid use, trial size and endpoints used) was the principal reason for the failures. Despite the lack of trial evidence, clinical experience means many physicians firmly believe in the value of rituximab in SLE/LN treatment and have continued to use it in their clinical practice. Recent work has demonstrated the efficacy of rituximab as a steroid-sparing agent and as an alternative therapeutic option for refractory SLE/LN. There are two further rituximab randomised controlled trials planned/started in LN – one using a steroid-minimising regimen with rituximab for induction and one evaluating rituximab for LN refractory to 6 months standard of care treatment. Rituximab remains a problematic drug in lupus and LN – it is a biologically plausible agent with a huge amount of supportive anecdotal clinical data. Yet the completed trials have been negative to date despite clinical experience strongly suggesting efficacy. It is hoped that the two new trials will determine the role for rituximab, at least in LN.

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  • Authors+Show Affiliations

    ,

    Imperial AHSC Lupus Centre, Department of Medicine, Imperial College London, London, UK.

    Source

    Nephron. Clinical practice 128:3-4 2014 pg 250-4

    MeSH

    Antibodies, Monoclonal, Murine-Derived
    Glucocorticoids
    Humans
    Immunologic Factors
    Lupus Erythematosus, Systemic
    Lupus Nephritis
    Rituximab

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    25471633

    Citation

    Beckwith, Hannah, and Liz Lightstone. "Rituximab in Systemic Lupus Erythematosus and Lupus Nephritis." Nephron. Clinical Practice, vol. 128, no. 3-4, 2014, pp. 250-4.
    Beckwith H, Lightstone L. Rituximab in systemic lupus erythematosus and lupus nephritis. Nephron Clin Pract. 2014;128(3-4):250-4.
    Beckwith, H., & Lightstone, L. (2014). Rituximab in systemic lupus erythematosus and lupus nephritis. Nephron. Clinical Practice, 128(3-4), pp. 250-4. doi:10.1159/000368585.
    Beckwith H, Lightstone L. Rituximab in Systemic Lupus Erythematosus and Lupus Nephritis. Nephron Clin Pract. 2014;128(3-4):250-4. PubMed PMID: 25471633.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Rituximab in systemic lupus erythematosus and lupus nephritis. AU - Beckwith,Hannah, AU - Lightstone,Liz, Y1 - 2014/11/29/ PY - 2014/12/5/entrez PY - 2014/12/5/pubmed PY - 2015/7/15/medline SP - 250 EP - 4 JF - Nephron. Clinical practice JO - Nephron Clin Pract VL - 128 IS - 3-4 N2 - Treatment options for systemic lupus erythematosus (SLE) and lupus nephritis (LN) have high associated morbidity and mortality. Side effects, particularly from long-term corticosteroid usage, limit patient adherence, with subsequent impacts on treatment efficacy. In addition, a subset of patients with SLE/LN fails to respond to current standard immunotherapy. There is an urgent need to develop steroid-sparing treatment regimens as well as novel therapies for the management of refractory disease. Rituximab is a chimeric mouse/human monoclonal antibody directed against the B cell CD20 receptor. It has been used in the treatment of non-Hodgkin's lymphoma for over 30 years and has an excellent safety profile. Recent work has demonstrated a role for B cell depletion therapy in the management of autoimmune disease, and the efficacy of rituximab in many observational studies in SLE and LN has been noted. Unfortunately, two large randomised controlled trials evaluating rituximab for the treatment of renal and non-renal lupus failed to meet their primary endpoints. Reasons for this have been discussed extensively within the medical community with a general consensus that trial design (steroid use, trial size and endpoints used) was the principal reason for the failures. Despite the lack of trial evidence, clinical experience means many physicians firmly believe in the value of rituximab in SLE/LN treatment and have continued to use it in their clinical practice. Recent work has demonstrated the efficacy of rituximab as a steroid-sparing agent and as an alternative therapeutic option for refractory SLE/LN. There are two further rituximab randomised controlled trials planned/started in LN – one using a steroid-minimising regimen with rituximab for induction and one evaluating rituximab for LN refractory to 6 months standard of care treatment. Rituximab remains a problematic drug in lupus and LN – it is a biologically plausible agent with a huge amount of supportive anecdotal clinical data. Yet the completed trials have been negative to date despite clinical experience strongly suggesting efficacy. It is hoped that the two new trials will determine the role for rituximab, at least in LN. SN - 1660-2110 UR - https://www.unboundmedicine.com/medline/citation/25471633/Rituximab_in_systemic_lupus_erythematosus_and_lupus_nephritis_ L2 - https://www.karger.com?DOI=10.1159/000368585 DB - PRIME DP - Unbound Medicine ER -