Efficacy and safety of tabalumab, an anti-B-cellactivating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy: Results from a phase III multicentre, randomised, double-blind study

Josef S. Smolen, Michael E. Weinblatt, Désirée Van Der Heijde, William F C Rigby, Ronald Van Vollenhoven, Clifton Bingham, Melissa Veenhuizen, Anne Gill, Fangyi Zhao, Wendy J. Komocsar, Pierre Yves Berclaz, Robert Ortmann, Chin Lee

Research output: Contribution to journalArticle

Abstract

Objectives Randomised, double-blind, placebocontrolled study to evaluate efficacy and safety of tabalumab in patients with rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX-IR). Methods 1041 patients with moderate'severe RA despite ongoing MTX enrolled in a 52-week study evaluating subcutaneous tabalumab 120 mg every four weeks (120/Q4W) or 90 mg every two weeks (90/ Q2W) versus placebo. Primary endpoints were American College of Rheumatology 20% (ACR20) response rate and Health Assessment Questionnaire-Disability Index change from baseline at 24 weeks and modified Total Sharp Score (mTSS) change at 52 weeks. Results There were no significant differences in ACR20 responses at week 24 or mTSS change from baseline at week 52 among treatment groups. Declines were seen in CD20+ B cells and immunoglobulin levels in tabalumab groups, but not placebo: B cells (-15.0%, -18.8%, 5.3%, in the 120/Q4W, 90/Q2W, and placebo groups, respectively); IgM (-16.3%, -19.4%, -0.1%), IgA (-11.4%, -4.7%, 1.2%) and IgG (-8.6%, -7.8%, 0.1%). Discontinuations due to adverse events were similar between groups. Numerically more serious infections were reported in tabalumab groups (1.7%, 0.6%, 0.3%); numerically more injection-site reactions were reported in the 90/Q2W group (2.3%, 4.3%, 2.3%). Conclusions Neither clinical efficacy nor significant safety signals were observed with tabalumab despite evidence of biological activity. This study was terminated early due to insufficient efficacy. Trial registration number NCT01198002.

Original languageEnglish (US)
Pages (from-to)1567-1570
Number of pages4
JournalAnnals of the Rheumatic Diseases
Volume74
Issue number8
DOIs
StatePublished - Aug 1 2015

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Double-Blind Method
Methotrexate
Rheumatoid Arthritis
Monoclonal Antibodies
Safety
Placebos
B-Lymphocytes
Cells
Therapeutics
Rheumatology
Bioactivity
Immunoglobulin A
Immunoglobulin M
Immunoglobulins
Immunoglobulin G
tabalumab
3'-(1-butylphosphoryl)adenosine
Health
Injections
Infection

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

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Efficacy and safety of tabalumab, an anti-B-cellactivating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy : Results from a phase III multicentre, randomised, double-blind study. / Smolen, Josef S.; Weinblatt, Michael E.; Van Der Heijde, Désirée; Rigby, William F C; Vollenhoven, Ronald Van; Bingham, Clifton; Veenhuizen, Melissa; Gill, Anne; Zhao, Fangyi; Komocsar, Wendy J.; Berclaz, Pierre Yves; Ortmann, Robert; Lee, Chin.

In: Annals of the Rheumatic Diseases, Vol. 74, No. 8, 01.08.2015, p. 1567-1570.

Research output: Contribution to journalArticle

Smolen, Josef S. ; Weinblatt, Michael E. ; Van Der Heijde, Désirée ; Rigby, William F C ; Vollenhoven, Ronald Van ; Bingham, Clifton ; Veenhuizen, Melissa ; Gill, Anne ; Zhao, Fangyi ; Komocsar, Wendy J. ; Berclaz, Pierre Yves ; Ortmann, Robert ; Lee, Chin. / Efficacy and safety of tabalumab, an anti-B-cellactivating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy : Results from a phase III multicentre, randomised, double-blind study. In: Annals of the Rheumatic Diseases. 2015 ; Vol. 74, No. 8. pp. 1567-1570.
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title = "Efficacy and safety of tabalumab, an anti-B-cellactivating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy: Results from a phase III multicentre, randomised, double-blind study",
abstract = "Objectives Randomised, double-blind, placebocontrolled study to evaluate efficacy and safety of tabalumab in patients with rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX-IR). Methods 1041 patients with moderate'severe RA despite ongoing MTX enrolled in a 52-week study evaluating subcutaneous tabalumab 120 mg every four weeks (120/Q4W) or 90 mg every two weeks (90/ Q2W) versus placebo. Primary endpoints were American College of Rheumatology 20{\%} (ACR20) response rate and Health Assessment Questionnaire-Disability Index change from baseline at 24 weeks and modified Total Sharp Score (mTSS) change at 52 weeks. Results There were no significant differences in ACR20 responses at week 24 or mTSS change from baseline at week 52 among treatment groups. Declines were seen in CD20+ B cells and immunoglobulin levels in tabalumab groups, but not placebo: B cells (-15.0{\%}, -18.8{\%}, 5.3{\%}, in the 120/Q4W, 90/Q2W, and placebo groups, respectively); IgM (-16.3{\%}, -19.4{\%}, -0.1{\%}), IgA (-11.4{\%}, -4.7{\%}, 1.2{\%}) and IgG (-8.6{\%}, -7.8{\%}, 0.1{\%}). Discontinuations due to adverse events were similar between groups. Numerically more serious infections were reported in tabalumab groups (1.7{\%}, 0.6{\%}, 0.3{\%}); numerically more injection-site reactions were reported in the 90/Q2W group (2.3{\%}, 4.3{\%}, 2.3{\%}). Conclusions Neither clinical efficacy nor significant safety signals were observed with tabalumab despite evidence of biological activity. This study was terminated early due to insufficient efficacy. Trial registration number NCT01198002.",
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T1 - Efficacy and safety of tabalumab, an anti-B-cellactivating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy

T2 - Results from a phase III multicentre, randomised, double-blind study

AU - Smolen, Josef S.

AU - Weinblatt, Michael E.

AU - Van Der Heijde, Désirée

AU - Rigby, William F C

AU - Vollenhoven, Ronald Van

AU - Bingham, Clifton

AU - Veenhuizen, Melissa

AU - Gill, Anne

AU - Zhao, Fangyi

AU - Komocsar, Wendy J.

AU - Berclaz, Pierre Yves

AU - Ortmann, Robert

AU - Lee, Chin

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Objectives Randomised, double-blind, placebocontrolled study to evaluate efficacy and safety of tabalumab in patients with rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX-IR). Methods 1041 patients with moderate'severe RA despite ongoing MTX enrolled in a 52-week study evaluating subcutaneous tabalumab 120 mg every four weeks (120/Q4W) or 90 mg every two weeks (90/ Q2W) versus placebo. Primary endpoints were American College of Rheumatology 20% (ACR20) response rate and Health Assessment Questionnaire-Disability Index change from baseline at 24 weeks and modified Total Sharp Score (mTSS) change at 52 weeks. Results There were no significant differences in ACR20 responses at week 24 or mTSS change from baseline at week 52 among treatment groups. Declines were seen in CD20+ B cells and immunoglobulin levels in tabalumab groups, but not placebo: B cells (-15.0%, -18.8%, 5.3%, in the 120/Q4W, 90/Q2W, and placebo groups, respectively); IgM (-16.3%, -19.4%, -0.1%), IgA (-11.4%, -4.7%, 1.2%) and IgG (-8.6%, -7.8%, 0.1%). Discontinuations due to adverse events were similar between groups. Numerically more serious infections were reported in tabalumab groups (1.7%, 0.6%, 0.3%); numerically more injection-site reactions were reported in the 90/Q2W group (2.3%, 4.3%, 2.3%). Conclusions Neither clinical efficacy nor significant safety signals were observed with tabalumab despite evidence of biological activity. This study was terminated early due to insufficient efficacy. Trial registration number NCT01198002.

AB - Objectives Randomised, double-blind, placebocontrolled study to evaluate efficacy and safety of tabalumab in patients with rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX-IR). Methods 1041 patients with moderate'severe RA despite ongoing MTX enrolled in a 52-week study evaluating subcutaneous tabalumab 120 mg every four weeks (120/Q4W) or 90 mg every two weeks (90/ Q2W) versus placebo. Primary endpoints were American College of Rheumatology 20% (ACR20) response rate and Health Assessment Questionnaire-Disability Index change from baseline at 24 weeks and modified Total Sharp Score (mTSS) change at 52 weeks. Results There were no significant differences in ACR20 responses at week 24 or mTSS change from baseline at week 52 among treatment groups. Declines were seen in CD20+ B cells and immunoglobulin levels in tabalumab groups, but not placebo: B cells (-15.0%, -18.8%, 5.3%, in the 120/Q4W, 90/Q2W, and placebo groups, respectively); IgM (-16.3%, -19.4%, -0.1%), IgA (-11.4%, -4.7%, 1.2%) and IgG (-8.6%, -7.8%, 0.1%). Discontinuations due to adverse events were similar between groups. Numerically more serious infections were reported in tabalumab groups (1.7%, 0.6%, 0.3%); numerically more injection-site reactions were reported in the 90/Q2W group (2.3%, 4.3%, 2.3%). Conclusions Neither clinical efficacy nor significant safety signals were observed with tabalumab despite evidence of biological activity. This study was terminated early due to insufficient efficacy. Trial registration number NCT01198002.

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