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Clinical Experience...
Clinical Experience of Proteasome Inhibitor Bortezomib Regarding Efficacy and Safety in Severe Systemic Lupus Erythematosus: A Nationwide Study
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- Walhelm, Tomas (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
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- Gunnarsson, I. (author)
- Karolinska Institutet,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
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- Heijke, R. (author)
- Dept Internal Med, Jönköping, Sweden.
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- Leonard, Dag, 1975- (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden
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- Trysberg, Estelle, 1960 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Univ Gothenburg, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden.
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- Eriksson, Per (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland,Dept Internal Med, Jönköping, Sweden
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- Sjöwall, Christopher (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
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(creator_code:org_t)
- 2021-10-01
- 2021
- English.
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Abstract
Subject headings
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- As treatment options in advanced systematic lupus erythematosus (SLE) are limited, there is an urgent need for new and effective therapeutic alternatives for selected cases with severe disease. Bortezomib (BTZ) is a specific, reversible, inhibitor of the 20S subunit of the proteasome. Herein, we report clinical experience regarding efficacy and safety from all patients receiving BTZ as therapy for SLE in Sweden during the years 2014-2020. 8 females and 4 males were included with a mean disease duration at BTZ initiation of 8.8 years (range 0.7-20 years). Renal involvement was the main target for BTZ. Reduction of global disease activity was recorded by decreasing SLEDAI-2K scores over time and remained significantly reduced at the 6-month (p=0.007) and the 12-month (p=0.008) follow-up visits. From BTZ initiation, complement protein 3 (C3) levels increased significantly after the 2(nd) treatment cycle (p=0.05), the 6-month (p=0.03) and the 12-month (p=0.04) follow-up visits. The urine albumin/creatinine ratio declined over time and reached significance at the 6-month (p=0.008) and the 12-month follow-up visits (p=0.004). Seroconversion of anti-dsDNA (27%), anti-C1q (50%) and anti-Sm (67%) was observed. 6 of 12 patients experienced at least one side-effect during follow-up, whereof the most common adverse events were infections. Safety parameters (C-reactive protein, blood cell counts) mainly remained stable over time. To conclude, we report favorable therapeutic effects of BTZ used in combination with corticosteroids in a majority of patients with severe SLE manifestations irresponsive to conventional immunosuppressive agents. Reduction of proteinuria was observed over time as well as seroconversion of some autoantibody specificities. In most patients, tolerance was acceptable but mild adverse events was not uncommon. Special attention should be paid to infections and hypogammaglobinemia.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- bortezomib (BTZ)
- systemic lupus
- erythematosus
- Lupus nephritis (LN)
- adverse (side) effects
- antinuclear antibodies
- clinical efficacy
- analysis
- observational study
- depletes plasma-cells
- disease
- classification
- index
- onset
- Immunology
- bortezomib (BTZ)
Publication and Content Type
- ref (subject category)
- art (subject category)
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