A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus

Daniel J. Wallace, William Stohl, Richard A. Furie, Jeffrey R. Lisse, James D. McKay, Joan T. Merrill, Michelle Petri, Ellen M. Ginzler, W. Winn Chatham, W. Joseph McCune, Vivian Fernandez, Marc R. Chevrier, Z. John Zhong, William W. Freimuth

Research output: Contribution to journalArticle

Abstract

Objective. To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). Methods. Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare. Results. Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer ≥1:80 and/or anti-double-stranded DNA [anti-dsDNA] ≥30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8% versus -14.2%; P = 0.0435), physician's global assessment (-32.7% versus -10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups. Conclusion. Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.

Original languageEnglish (US)
Pages (from-to)1168-1178
Number of pages11
JournalArthritis Care and Research
Volume61
Issue number9
DOIs
StatePublished - Sep 15 2009

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Systemic Lupus Erythematosus
Placebos
Safety
Estrogens
Standard of Care
Therapeutics
belimumab
Antinuclear Antibodies
B-Lymphocytes
Physicians
DNA

ASJC Scopus subject areas

  • Rheumatology

Cite this

Wallace, D. J., Stohl, W., Furie, R. A., Lisse, J. R., McKay, J. D., Merrill, J. T., ... Freimuth, W. W. (2009). A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Care and Research, 61(9), 1168-1178. https://doi.org/10.1002/art.24699

A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. / Wallace, Daniel J.; Stohl, William; Furie, Richard A.; Lisse, Jeffrey R.; McKay, James D.; Merrill, Joan T.; Petri, Michelle; Ginzler, Ellen M.; Chatham, W. Winn; McCune, W. Joseph; Fernandez, Vivian; Chevrier, Marc R.; Zhong, Z. John; Freimuth, William W.

In: Arthritis Care and Research, Vol. 61, No. 9, 15.09.2009, p. 1168-1178.

Research output: Contribution to journalArticle

Wallace, DJ, Stohl, W, Furie, RA, Lisse, JR, McKay, JD, Merrill, JT, Petri, M, Ginzler, EM, Chatham, WW, McCune, WJ, Fernandez, V, Chevrier, MR, Zhong, ZJ & Freimuth, WW 2009, 'A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus', Arthritis Care and Research, vol. 61, no. 9, pp. 1168-1178. https://doi.org/10.1002/art.24699
Wallace, Daniel J. ; Stohl, William ; Furie, Richard A. ; Lisse, Jeffrey R. ; McKay, James D. ; Merrill, Joan T. ; Petri, Michelle ; Ginzler, Ellen M. ; Chatham, W. Winn ; McCune, W. Joseph ; Fernandez, Vivian ; Chevrier, Marc R. ; Zhong, Z. John ; Freimuth, William W. / A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. In: Arthritis Care and Research. 2009 ; Vol. 61, No. 9. pp. 1168-1178.
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abstract = "Objective. To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). Methods. Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare. Results. Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5{\%} in the combined belimumab group versus 17.2{\%} in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5{\%}) of serologically active patients (antinuclear antibody titer ≥1:80 and/or anti-double-stranded DNA [anti-dsDNA] ≥30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8{\%} versus -14.2{\%}; P = 0.0435), physician's global assessment (-32.7{\%} versus -10.7{\%}; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71{\%} reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4{\%} reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups. Conclusion. Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.",
author = "Wallace, {Daniel J.} and William Stohl and Furie, {Richard A.} and Lisse, {Jeffrey R.} and McKay, {James D.} and Merrill, {Joan T.} and Michelle Petri and Ginzler, {Ellen M.} and Chatham, {W. Winn} and McCune, {W. Joseph} and Vivian Fernandez and Chevrier, {Marc R.} and Zhong, {Z. John} and Freimuth, {William W.}",
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T1 - A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus

AU - Wallace, Daniel J.

AU - Stohl, William

AU - Furie, Richard A.

AU - Lisse, Jeffrey R.

AU - McKay, James D.

AU - Merrill, Joan T.

AU - Petri, Michelle

AU - Ginzler, Ellen M.

AU - Chatham, W. Winn

AU - McCune, W. Joseph

AU - Fernandez, Vivian

AU - Chevrier, Marc R.

AU - Zhong, Z. John

AU - Freimuth, William W.

PY - 2009/9/15

Y1 - 2009/9/15

N2 - Objective. To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). Methods. Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare. Results. Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer ≥1:80 and/or anti-double-stranded DNA [anti-dsDNA] ≥30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8% versus -14.2%; P = 0.0435), physician's global assessment (-32.7% versus -10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups. Conclusion. Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.

AB - Objective. To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). Methods. Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare. Results. Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer ≥1:80 and/or anti-double-stranded DNA [anti-dsDNA] ≥30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8% versus -14.2%; P = 0.0435), physician's global assessment (-32.7% versus -10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups. Conclusion. Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.

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