Moots, Robert J., Sebba, Anthony, Rigby, William, Ostor, Andrew, Porter-Brown, Benjamin, Donaldson, Francis, Dimonaco, Sophie, Rubbert-Roth, Andrea, van Vollenhoven, Ronald and Genovese, Mark C. (2017). Effect of tocilizumab on neutrophils in adult patients with rheumatoid arthritis: pooled analysis of data from phase 3 and 4 clinical trials. RHEUMATOLOGY, 56 (4). S. 541 - 550. OXFORD: OXFORD UNIV PRESS. ISSN 1462-0332

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Abstract

Objectives. To investigate changes in neutrophil count and occurrences of infection in RA patients treated with the IL-6 receptor-alpha inhibitor tocilizumab (TCZ). Methods. Data were pooled from patients who received i.v. TCZ (4 mg/kg + MTX, 8 mg/kg +/- DMARDs, 10 mg/kg) or placebo + DMARDs in phase 3/4 clinical trials, long-term extensions or a pharmacology study. Neutrophil counts were measured routinely according to the Common Toxicity Criteria for Adverse Events grades; TCZ dosing was adjusted if necessary. Covariates associated with decreased neutrophil counts were assessed with multivariate regression analysis. Infection rates within 30 days of neutrophil count changes were calculated per 100 patient-years of TCZ exposure. Results. In placebo-controlled parts of trials, more TCZ-treated than placebo-treated patients had grade 1/2 or 3/4 neutrophil counts (TCZ: 28.2%/3.1%; placebo: 8.9%/0.2%). In placebo-controlled trials + long-term extensions, 4171 patients provided 16204.8 patient-years of TCZ exposure. Neutrophil counts decreased through week 6 from baseline [mean (s.d.) change, -2.17 (2.16) x 10(9)/l) and remained stable thereafter. Rates (95% CI) of serious infections within 30 days of normal [4.66 (4.31, 5.03)], grade 1/2 [2.48 (1.79, 3.34)] and 3/4 [2.77 (0.34, 10.01)] neutrophil counts were similar. Baseline neutrophil count < 2 x 10(9)/l and female gender were associated with grade 3/4 neutrophil counts [odds ratio (OR) (95% CI): 19.02 (6.76, 53.52), 2.55 (1.40, 4.66)]. Patients who stopped TCZ in response to decreased neutrophil count returned more quickly to normal levels than patients who reduced or continued their dose. Conclusion. Decreases in neutrophil counts in patients taking TCZ do not appear to be associated with serious infections and are normalized by current risk mitigation guidelines.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Moots, Robert J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sebba, AnthonyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rigby, WilliamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ostor, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Porter-Brown, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Donaldson, FrancisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dimonaco, SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubbert-Roth, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Vollenhoven, RonaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Genovese, Mark C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-235692
DOI: 10.1093/rheumatology/kew370
Journal or Publication Title: RHEUMATOLOGY
Volume: 56
Number: 4
Page Range: S. 541 - 550
Date: 2017
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1462-0332
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MODIFYING ANTIRHEUMATIC DRUGS; INTERLEUKIN-6 RECEPTOR INHIBITION; DOUBLE-BLIND; SUBCUTANEOUS TOCILIZUMAB; SERIOUS INFECTIONS; IL-6 RECEPTOR; DISEASE; COMBINATION; APOPTOSIS; THERAPYMultiple languages
RheumatologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23569

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