ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 273

Neutropenia With Tocilizumab Treatment Is Not Associated With Increased Infection Risk In Patients With Systemic Juvenile Idiopathic Arthritis

Fabrizio De Benedetti1, Hermine Brunner2, Eileen M. Baildam3, Ruben Burgos-Vargas3, Gerd Horneff3, Hans-Iko Huppertz3, Kirsten Minden4, Barry L. Myones2, Karen Onel5, Jianmei Wang6, Kamal N. Bharucha7, Daniel J. Lovell2, Alberto Martini8 and Nicolino Ruperto3, 1IRCCS Ospedale Pediatrico Bambino Gesú, Rome, Italy, 2PRCSG, Cincinnati, OH, 3PRINTO, Genoa, Italy, 4Children’s University Hospital Charite/German Rheumatism Research Centre Berlin, Berlin, Germany, 5Pediatric Rheumatology, University of Chicago Hospitals, Chicago, IL, 6Roche Products Ltd., Welwyn Garden City, United Kingdom, 7Genentech, South San Francisco, CA, 8Pediatria II, Istituto Giannina Gaslini, Genova, Italy

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects I: Juvenile Idiopathic Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: In the phase 3 TENDER trial of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA), decreases in neutrophil count were commonly observed. The purpose of this analysis was to determine if neutropenia was associated with increased risk of infection and to investigate variables associated with development of neutropenia in patients treated with TCZ for up to 2 years in TENDER.

Methods: One hundred twelve children with active, persistent sJIA were randomized 2:1 to receive TCZ by body weight (12 mg/kg <30 kg or 8 mg/kg ≥30 kg) or placebo IV every 2 weeks for 12 weeks and continued in an ongoing TCZ open-label extension.1 Worst Common Toxicity Criteria (CTC) neutropenia grade (grade 1, ≥1.5 and <2.0×109/L; grade 2, ≥1.0 and <1.5×109/L; grade 3, ≥0.5 and <1.0×109/L; grade 4, <0.5×109/L) and lowest observed neutrophil count (109/L) were identified for each patient. Univariate linear regression analysis was performed to investigate association of patient characteristics with lowest observed neutrophil count. Rates of infections and serious infections (per 100 patient years [PY]) in periods ±15 days around grade1-2 neutropenia (22.9 PY) and around grade 3-4 neutropenia (5.5 PY) were compared to corresponding rates in periods with normal neutrophil count (173.6 PY).

Results: Up to week 104, 64/112 patients (57.1%) had at least 1 episode of grade 1-4 neutropenia; worst grade: 1 (n=2), 2 (n=34), 3 (n=26), and 4 (n=2). Rates of infections and serious infections during period of normal neutrophil counts (276.5/100 PY [95% CI: 252.3, 302.3] and 11.5/100 PY [95% CI: 7.0, 17.8], respectively) were comparable to those observed ±15 days around grade 1-2 neutropenia (226.7/100 PY [95% CI: 169.3, 297.3]; 8.7/100 PY [95% CI: 1.1, 31.5]) and grade 3-4 neutropenia (292.5/100 PY [95% CI: 167.2, 475.0]; 0/100 PY), with no trend toward increased risk with higher grade neutropenia. Methotrexate (MTX) use (Yes/No) was significantly associated with lowest observed neutrophil count (difference: –0.575 [95% CI: –1.02, –0.13], p=0.012), with 62% of 77 patients receiving MTX vs 46% of 35 patients not receiving MTX having grade 1-4 neutropenia. Younger age was borderline associated with lowest observed neutrophil count (β=0.04661, p=0.047). Concurrent use of glucocorticoids (GC) and TCZ exposure were not associated with lowest observed neutrophil count (p>0.3).

 Conclusion: No trend for association between neutropenia and increased risk of infections was observed in the TENDER trial. Background MTX, and somewhat younger age, was associated with increased risk of neutropenia, while TCZ exposure and concurrent GC use were not. Reference: 1. De Benedetti F et al. N Engl J Med 2012;367:2385.

Disclosure:

F. De Benedetti,

Abbott, Pfizer, BMS, Roche, Novimmune, Novartis, SOBI,

2;

H. Brunner,

Novartis, Genentech, Medimmune, EMD Serono, AMS, Pfizer, UCB, Janssen,

5,

Genentech ,

8;

E. M. Baildam,
None;

R. Burgos-Vargas,

Abbott, BMS, Janssen, Pfizer, Roche,

5,

Abbott, BMS, Janssen, Pfizer, Roche,

8,

Abbott Immunology Pharmaceuticals,

2;

G. Horneff,

Abbott, Pfizer,

2;

H. I. Huppertz,

Abbott, Chugai, Pfizer, Roche, Swedish Orphan,

5;

K. Minden,

Pfizer, Abbvie, Roche, Chugai, Medac,

5,

Pfizer, Abbvie,

2;

B. L. Myones,
None;

K. Onel,
None;

J. Wang,

Roche Pharmaceuticals,

3;

K. N. Bharucha,

Genentech and Biogen IDEC Inc.,

3;

D. J. Lovell,

NIH,

2,

AstraZeneca, Centocor, Janssen, Wyeth, Amgen, Bristol-Meyers Squibb, Abbott, Pfizer, Regeneron, Hoffmann-La Roche, Novartis, Genentech,

5,

Roche, Genentech,

8;

A. Martini,

Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, MerckSerono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth,

2,

Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, MerckSerono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth,

5,

Abbott, Boehringer, BMS, Novartis, Astellas, Italfarmaco, MedImmune, Pfizer, Roche,

8;

N. Ruperto,

To Gaslini Hospital: Abbott, Astrazeneca, BMS, Centocor Research & Development, Eli Lilly and Company, “Francesco Angelini”, Glaxo Smith & Kline, Italfarmaco, Novartis, Pfizer Inc., Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuti,

2,

Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Roche, Wyeth, Pfizer,

8.

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