Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

Mikkel Østergaard; Bo Baslund; William Rigby; Bernadette Rojkovich; Christian Jorgensen; Peter T Dawes; Charlotte Wiell; Daniel J Wallace; Søren C Tamer; Helle Kastberg; Jørgen Petersen; Stanislaw Sierakowski

doi:10.1002/art.27524

Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

Mikkel Østergaard, Bo Baslund, William Rigby, Bernadette Rojkovich, Christian Jorgensen, Peter T Dawes, Charlotte Wiell, Daniel J Wallace, Søren C Tamer, Helle Kastberg, Jørgen Petersen, Stanislaw Sierakowski

79 Citations (Scopus)

Abstract

Objective. To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to ≥1 disease-modifying antirheumatic drug. Methods. This combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (IV) infusions of ofatumumab (300 mg, 700 mg, or 1,000 mg) or placebo in a 4:1 ratio 2 weeks apart, using a specified premedication and infusion regimen. In part B (phase II), 225 patients received study treatment as per phase I in a 1:1:1:1 ratio. Safety was assessed by adverse events (AEs) and laboratory parameters. Efficacy was assessed by the American College of Rheumatology 20% criteria for improvement (ACR20), the Disease Activity Score in 28 joints, and the European League Against Rheumatism (EULAR) response criteria. B cell pharmacodynamics were also investigated. Results. AEs were predominantly reported at the first infusion and were mostly mild to moderate in intensity. Rapid and sustained peripheral B cell depletion was observed in all dose groups. In phase II, patients in all ofatumumab dose groups had significantly higher ACR20 response rates (40%, 49%, and 44% for the 300 mg, 700 mg, and 1,000 mg doses, respectively) than did patients receiving placebo (11%) at week 24 (P < 0.001). Overall, 70% of patients receiving ofatumumab had a moderate or good response according to the EULAR criteria at week 24. Conclusion. Our findings indicate that ofatumumab, administered as 2 IV infusions of doses up to 1,000 mg, is clinically effective in patients with active RA.

Original language	English
Journal	Arthritis & Rheumatism
Volume	62
Issue number	8
Pages (from-to)	2227-38
Number of pages	12
ISSN	0004-3591
DOIs	https://doi.org/10.1002/art.27524
Publication status	Published - 1 Aug 2010

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Østergaard, M., Baslund, B., Rigby, W., Rojkovich, B., Jorgensen, C., Dawes, P. T., Wiell, C., Wallace, D. J., Tamer, S. C., Kastberg, H., Petersen, J., & Sierakowski, S. (2010). Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis & Rheumatism, 62(8), 2227-38. https://doi.org/10.1002/art.27524

Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. / Østergaard, Mikkel; Baslund, Bo; Rigby, William et al.

In: Arthritis & Rheumatism, Vol. 62, No. 8, 01.08.2010, p. 2227-38.

Research output: Contribution to journal › Journal article › Research › peer-review

Østergaard, M, Baslund, B, Rigby, W, Rojkovich, B, Jorgensen, C, Dawes, PT, Wiell, C, Wallace, DJ, Tamer, SC, Kastberg, H, Petersen, J & Sierakowski, S 2010, 'Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study', Arthritis & Rheumatism, vol. 62, no. 8, pp. 2227-38. https://doi.org/10.1002/art.27524

Østergaard M, Baslund B, Rigby W, Rojkovich B, Jorgensen C, Dawes PT et al. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis & Rheumatism. 2010 Aug 1;62(8):2227-38. doi: 10.1002/art.27524

Østergaard, Mikkel ; Baslund, Bo ; Rigby, William et al. / Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. In: Arthritis & Rheumatism. 2010 ; Vol. 62, No. 8. pp. 2227-38.

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T1 - Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

AU - Østergaard, Mikkel

AU - Baslund, Bo

AU - Rigby, William

AU - Rojkovich, Bernadette

AU - Jorgensen, Christian

AU - Dawes, Peter T

AU - Wiell, Charlotte

AU - Wallace, Daniel J

AU - Tamer, Søren C

AU - Kastberg, Helle

AU - Petersen, Jørgen

AU - Sierakowski, Stanislaw

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Objective. To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to ≥1 disease-modifying antirheumatic drug. Methods. This combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (IV) infusions of ofatumumab (300 mg, 700 mg, or 1,000 mg) or placebo in a 4:1 ratio 2 weeks apart, using a specified premedication and infusion regimen. In part B (phase II), 225 patients received study treatment as per phase I in a 1:1:1:1 ratio. Safety was assessed by adverse events (AEs) and laboratory parameters. Efficacy was assessed by the American College of Rheumatology 20% criteria for improvement (ACR20), the Disease Activity Score in 28 joints, and the European League Against Rheumatism (EULAR) response criteria. B cell pharmacodynamics were also investigated. Results. AEs were predominantly reported at the first infusion and were mostly mild to moderate in intensity. Rapid and sustained peripheral B cell depletion was observed in all dose groups. In phase II, patients in all ofatumumab dose groups had significantly higher ACR20 response rates (40%, 49%, and 44% for the 300 mg, 700 mg, and 1,000 mg doses, respectively) than did patients receiving placebo (11%) at week 24 (P < 0.001). Overall, 70% of patients receiving ofatumumab had a moderate or good response according to the EULAR criteria at week 24. Conclusion. Our findings indicate that ofatumumab, administered as 2 IV infusions of doses up to 1,000 mg, is clinically effective in patients with active RA.

AB - Objective. To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to ≥1 disease-modifying antirheumatic drug. Methods. This combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (IV) infusions of ofatumumab (300 mg, 700 mg, or 1,000 mg) or placebo in a 4:1 ratio 2 weeks apart, using a specified premedication and infusion regimen. In part B (phase II), 225 patients received study treatment as per phase I in a 1:1:1:1 ratio. Safety was assessed by adverse events (AEs) and laboratory parameters. Efficacy was assessed by the American College of Rheumatology 20% criteria for improvement (ACR20), the Disease Activity Score in 28 joints, and the European League Against Rheumatism (EULAR) response criteria. B cell pharmacodynamics were also investigated. Results. AEs were predominantly reported at the first infusion and were mostly mild to moderate in intensity. Rapid and sustained peripheral B cell depletion was observed in all dose groups. In phase II, patients in all ofatumumab dose groups had significantly higher ACR20 response rates (40%, 49%, and 44% for the 300 mg, 700 mg, and 1,000 mg doses, respectively) than did patients receiving placebo (11%) at week 24 (P < 0.001). Overall, 70% of patients receiving ofatumumab had a moderate or good response according to the EULAR criteria at week 24. Conclusion. Our findings indicate that ofatumumab, administered as 2 IV infusions of doses up to 1,000 mg, is clinically effective in patients with active RA.

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DO - 10.1002/art.27524

M3 - Journal article

SN - 2326-5205

VL - 62

SP - 2227

EP - 2238

JO - Arthritis & Rheumatology

JF - Arthritis & Rheumatology

IS - 8

ER -