Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus

Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials

on behalf of the EMBODY Investigator Group

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Objective: Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). Methods: Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti–double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5–60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. Results: In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified. Conclusion: In patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.

Original languageEnglish (US)
Pages (from-to)362-375
Number of pages14
JournalArthritis and Rheumatology
Volume69
Issue number2
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

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Systemic Lupus Erythematosus
Placebos
Safety
B-Lymphocytes
Therapeutics
epratuzumab
Antinuclear Antibodies
Group Psychotherapy
Adrenal Cortex Hormones
Central Nervous System
Monoclonal Antibodies
Physicians
Kidney
Antibodies
DNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus : Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials. / on behalf of the EMBODY Investigator Group.

In: Arthritis and Rheumatology, Vol. 69, No. 2, 01.02.2017, p. 362-375.

Research output: Contribution to journalArticle

@article{88a90d8ef69e47c6bd53572b9a37d6d9,
title = "Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials",
abstract = "Objective: Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). Methods: Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti–double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5–60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. Results: In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1{\%}) and 788 (99.6{\%}), respectively, received study medication, and 528 (66.6{\%}) and 533 (67.4{\%}), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5{\%} to 39.8{\%}). No new safety signals were identified. Conclusion: In patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.",
author = "{on behalf of the EMBODY Investigator Group} and Clowse, {Megan E B} and Wallace, {Daniel J.} and Furie, {Richard A.} and Petri, {Michelle A.} and Pike, {Marilyn C.} and Piotr Leszczyński and Neuwelt, {C. Michael} and Kathryn Hobbs and Mauro Keiserman and Liliana Duca and Kalunian, {Kenneth C.} and Catrinel Galateanu and Sabine Bongardt and Christian Stach and Carolyn Beaudot and Brian Kilgallen and Caroline Gordon and A. Batalov and M. Bojinca and R. Djerassi and L. Duca and P. Horak and Z. Kolarov and R. Milasiene and D. Monova and K. Otsa and M. Pileckyte and T. Popova and F. Radulescu and R. Rashkov and S. Rednic and M. Repin and R. Stoilov and D. Tegzova and N. Vezikova and P. Vitek and C. Zainea and Far East and H. Baek and Y. Chen and Y. Chiu and C. Cho and C. Chou and J. Choe and C. Huang and Y. Kang and S. Kang and N. Lai and S. Lee and M Khan",
year = "2017",
month = "2",
day = "1",
doi = "10.1002/art.39856",
language = "English (US)",
volume = "69",
pages = "362--375",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "2",

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TY - JOUR

T1 - Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus

T2 - Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials

AU - on behalf of the EMBODY Investigator Group

AU - Clowse, Megan E B

AU - Wallace, Daniel J.

AU - Furie, Richard A.

AU - Petri, Michelle A.

AU - Pike, Marilyn C.

AU - Leszczyński, Piotr

AU - Neuwelt, C. Michael

AU - Hobbs, Kathryn

AU - Keiserman, Mauro

AU - Duca, Liliana

AU - Kalunian, Kenneth C.

AU - Galateanu, Catrinel

AU - Bongardt, Sabine

AU - Stach, Christian

AU - Beaudot, Carolyn

AU - Kilgallen, Brian

AU - Gordon, Caroline

AU - Batalov, A.

AU - Bojinca, M.

AU - Djerassi, R.

AU - Duca, L.

AU - Horak, P.

AU - Kolarov, Z.

AU - Milasiene, R.

AU - Monova, D.

AU - Otsa, K.

AU - Pileckyte, M.

AU - Popova, T.

AU - Radulescu, F.

AU - Rashkov, R.

AU - Rednic, S.

AU - Repin, M.

AU - Stoilov, R.

AU - Tegzova, D.

AU - Vezikova, N.

AU - Vitek, P.

AU - Zainea, C.

AU - East, Far

AU - Baek, H.

AU - Chen, Y.

AU - Chiu, Y.

AU - Cho, C.

AU - Chou, C.

AU - Choe, J.

AU - Huang, C.

AU - Kang, Y.

AU - Kang, S.

AU - Lai, N.

AU - Lee, S.

AU - Khan, M

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Objective: Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). Methods: Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti–double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5–60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. Results: In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified. Conclusion: In patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.

AB - Objective: Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). Methods: Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti–double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5–60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. Results: In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified. Conclusion: In patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.

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