Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus : A Randomized Controlled Trial
BACKGROUND: B-cell depletion with rituximab is commonly used for patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, but it yields variable responses. We hypothesized that high B-cell activating factor (BAFF) levels after rituximab can cause disease flares, thereby limiting its effectiveness.
OBJECTIVE: To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE.
DESIGN: Phase 2, randomized, double-blind (patients, assessors, researchers, care providers), placebo-controlled, parallel-group, superiority trial. (ISRCTN: 47873003).
SETTING: England.
PARTICIPANTS: Fifty-two patients who had SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy were recruited between 2 February 2017 and 28 March 2019.
INTERVENTION: Participants were treated with rituximab and 4 to 8 weeks later were randomly assigned (1:1) to receive intravenous belimumab or placebo for 52 weeks.
MEASUREMENTS: The prespecified primary end point was serum IgG anti-double-stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes included incidence of disease flares and adverse events.
RESULTS: At 52 weeks, IgG anti-dsDNA antibody levels were lower in patients treated with belimumab compared with placebo (geometric mean, 47 [95% CI, 25 to 88] vs. 103 [CI, 49 to 213] IU/mL; 70% greater reduction from baseline [CI, 46% to 84%]; P < 0.001). Belimumab reduced risk for severe flare (BILAG-2004 grade A) compared with placebo (hazard ratio, 0.27 [CI, 0.07 to 0.98]; log-rank P = 0.033), with 10 severe flares in the placebo group and 3 in the belimumab group. Belimumab did not increase incidence of serious adverse events. Belimumab significantly suppressed B-cell repopulation compared with placebo (geometric mean, 0.012 [CI, 0.006 to 0.014] vs. 0.037 [CI, 0.021 to 0.081] × 109/L) at 52 weeks in a subset of patients (n = 25) with available data.
LIMITATIONS: Small sample size; biomarker primary end point.
CONCLUSION: Belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced risk for severe flare in patients with SLE that was refractory to conventional therapy. The results suggest that this combination could be developed as a therapeutic strategy.
PRIMARY FUNDING SOURCE: Versus Arthritis.
| Errataetall: |
CommentIn: Ann Intern Med. 2021 Dec;174(12):1747-1748. - PMID 34698512 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:174 |
|---|---|
| Enthalten in: |
Annals of internal medicine - 174(2021), 12 vom: 04. Dez., Seite 1647-1657 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shipa, Muhammad [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.02.2022 Date Revised 15.07.2022 published: Print-Electronic CommentIn: Ann Intern Med. 2021 Dec;174(12):1747-1748. - PMID 34698512 Citation Status MEDLINE |
|---|
| doi: |
10.7326/M21-2078 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM332385604 |
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| 100 | 1 | |a Shipa, Muhammad |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus |b A Randomized Controlled Trial |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 14.02.2022 | ||
| 500 | |a Date Revised 15.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Ann Intern Med. 2021 Dec;174(12):1747-1748. - PMID 34698512 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: B-cell depletion with rituximab is commonly used for patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, but it yields variable responses. We hypothesized that high B-cell activating factor (BAFF) levels after rituximab can cause disease flares, thereby limiting its effectiveness | ||
| 520 | |a OBJECTIVE: To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE | ||
| 520 | |a DESIGN: Phase 2, randomized, double-blind (patients, assessors, researchers, care providers), placebo-controlled, parallel-group, superiority trial. (ISRCTN: 47873003) | ||
| 520 | |a SETTING: England | ||
| 520 | |a PARTICIPANTS: Fifty-two patients who had SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy were recruited between 2 February 2017 and 28 March 2019 | ||
| 520 | |a INTERVENTION: Participants were treated with rituximab and 4 to 8 weeks later were randomly assigned (1:1) to receive intravenous belimumab or placebo for 52 weeks | ||
| 520 | |a MEASUREMENTS: The prespecified primary end point was serum IgG anti-double-stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes included incidence of disease flares and adverse events | ||
| 520 | |a RESULTS: At 52 weeks, IgG anti-dsDNA antibody levels were lower in patients treated with belimumab compared with placebo (geometric mean, 47 [95% CI, 25 to 88] vs. 103 [CI, 49 to 213] IU/mL; 70% greater reduction from baseline [CI, 46% to 84%]; P < 0.001). Belimumab reduced risk for severe flare (BILAG-2004 grade A) compared with placebo (hazard ratio, 0.27 [CI, 0.07 to 0.98]; log-rank P = 0.033), with 10 severe flares in the placebo group and 3 in the belimumab group. Belimumab did not increase incidence of serious adverse events. Belimumab significantly suppressed B-cell repopulation compared with placebo (geometric mean, 0.012 [CI, 0.006 to 0.014] vs. 0.037 [CI, 0.021 to 0.081] × 109/L) at 52 weeks in a subset of patients (n = 25) with available data | ||
| 520 | |a LIMITATIONS: Small sample size; biomarker primary end point | ||
| 520 | |a CONCLUSION: Belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced risk for severe flare in patients with SLE that was refractory to conventional therapy. The results suggest that this combination could be developed as a therapeutic strategy | ||
| 520 | |a PRIMARY FUNDING SOURCE: Versus Arthritis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Video-Audio Media | |
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| 700 | 1 | |a Embleton-Thirsk, Andrew |e verfasserin |4 aut | |
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| 700 | 1 | |a Santos, Liliana Ribeiro |e verfasserin |4 aut | |
| 700 | 1 | |a Muller, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Chowdhury, Kashfia |e verfasserin |4 aut | |
| 700 | 1 | |a Isenberg, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Doré, Caroline J |e verfasserin |4 aut | |
| 700 | 1 | |a Gordon, Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a Ehrenstein, Michael R |e verfasserin |4 aut | |
| 700 | 0 | |a BEAT-LUPUS Investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Isenberg, David A |e investigator |4 oth | |
| 700 | 1 | |a Gordon, Caroline |e investigator |4 oth | |
| 700 | 1 | |a D'Cruz, David P |e investigator |4 oth | |
| 700 | 1 | |a Jordan, Natasha |e investigator |4 oth | |
| 700 | 1 | |a Parker, Benjamin |e investigator |4 oth | |
| 700 | 1 | |a Lightstone, Liz |e investigator |4 oth | |
| 700 | 1 | |a Salama, Alan |e investigator |4 oth | |
| 700 | 1 | |a Hamour, Sally |e investigator |4 oth | |
| 700 | 1 | |a Pyne, Deborah |e investigator |4 oth | |
| 700 | 1 | |a Edwards, Christopher J |e investigator |4 oth | |
| 700 | 1 | |a Griffiths, Bridget |e investigator |4 oth | |
| 700 | 1 | |a Vital, Edward M |e investigator |4 oth | |
| 700 | 1 | |a Rhodes, Benjamin |e investigator |4 oth | |
| 700 | 1 | |a Yee, Chee-Seng |e investigator |4 oth | |
| 700 | 1 | |a Akil, Mohammed |e investigator |4 oth | |
| 700 | 1 | |a Topham, Peter |e investigator |4 oth | |
| 700 | 1 | |a Gullick, Nicola J |e investigator |4 oth | |
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