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A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.
Arthritis Rheum 2009; 61(9):1168-78AR

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.

Authors+Show Affiliations

Cedars-Sinai Medical Center, University of California, Los Angeles, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19714604

Citation

Wallace, Daniel J., et al. "A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study of Belimumab in Patients With Active Systemic Lupus Erythematosus." Arthritis and Rheumatism, vol. 61, no. 9, 2009, pp. 1168-78.
Wallace DJ, Stohl W, Furie RA, et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum. 2009;61(9):1168-78.
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 and Rheumatism, 61(9), pp. 1168-78. doi:10.1002/art.24699.
Wallace DJ, et al. A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study of Belimumab in Patients With Active Systemic Lupus Erythematosus. Arthritis Rheum. 2009 Sep 15;61(9):1168-78. PubMed PMID: 19714604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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 A, 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 - 2009/8/29/entrez PY - 2009/8/29/pubmed PY - 2009/10/17/medline SP - 1168 EP - 78 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 61 IS - 9 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/19714604/A_phase_II_randomized_double_blind_placebo_controlled_dose_ranging_study_of_belimumab_in_patients_with_active_systemic_lupus_erythematosus_ L2 - https://doi.org/10.1002/art.24699 DB - PRIME DP - Unbound Medicine ER -