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OP0103 Identification of optimal subcutaneous doses of tocilizumab in children with systemic juvenile idiopathic arthritis
  1. H. Brunner1,
  2. N. Ruperto2,
  3. D. Lovell1,
  4. I. Calvo-Penedes3,
  5. G. Horneff4,
  6. M.L. Gamir Gamir5,
  7. M. Hufnagel6,
  8. J. Hsu7,
  9. M. Bao7,
  10. W. Douglass8,
  11. N.L. Mallalieu7,
  12. C. Wells8,
  13. C.M. Mela8,
  14. F. De Benedetti9,
  15. on behalf of PRINTO and PRCSG Investigators
  1. 1Cincinnati Children’s Hosp Med Ctr, Cincinnati, USA
  2. 2Istituto Giannina Gaslini, Pediatria II–Reumatologia, PRINTO, Genoa, Italy
  3. 3Hosp Universitario y Politécnico La Fe, Valencia, Spain
  4. 4Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany
  5. 5Hosp Ramon y Cajal, Madrid, Spain
  6. 6Universitätsklinikum Freiburg, Freiburg, Germany
  7. 7Roche Innovation Ctr, New York, USA
  8. 8Roche Products Ltd, Welwyn Garden City, UK
  9. 9IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

Abstract

Background Efficacy and safety of intravenous (IV) tocilizumab (TCZ) were demonstrated in patients (pts) with systemic juvenile idiopathic arthritis (sJIA) in the phase 3 TENDER study1 (WA18221). Study WA28118 (ClinicalTrials.gov, NCT01904292) investigated dosing regimens of subcutaneous (SC) TCZ in pts with sJIA by bridging to IV TCZ data to identify the optimal SC regimen.

Objectives To characterise the pharmacokinetics (PK), pharmacodynamics (PD), and safety of TCZ SC in pts with sJIA; efficacy was an exploratory objective.

Methods This phase 1b multicenter, open-label study evaluated PK, PD, and safety of TCZ SC in pts aged 1–17 years with sJIA and inadequate response to glucocorticoids and nonsteroidal anti-inflammatory drugs. Interim analysis (IA) was conducted after 24 pts had received TCZ SC for 14 weeks. Pts could be either TCZ-naive or switch from TCZ IV to SC at baseline. TCZ SC was administered for 52 weeks according to body weight:<30 kg, either 162 mg every 10 days (before IA) or 162 mg every 2 weeks (Q2W, after IA); ≥30 kg, 162 mg every week (QW).

Results Among enrolled pts (n=51), 25 weighed <30 kg (8 before and 17 after IA) and 26 weighed ≥30 kg. Twenty-six pts (51%) were TCZ naive and 25 (49%) switched from TCZ IV. Median steady state Cmin was similar for pts<30 kg receiving TCZ 162 mg Q2W and those ≥30 kg receiving TCZ 162 mg QW, and the range largely overlapped (table 1). More than 95% (49/51) of pts treated with TCZ SC had model-computed steady state Cmin higher than the 5th percentile achieved with TCZ IV. Median and range of AUC2weeks were similar for both weight groups (table 1). Changes in interleukin-6, C-reactive protein, and erythrocyte sedimentation rate were similar for both weight groups. Most pts had ≥1 adverse event (AE; n=50; 98%). Injection site reactions (ISRs) occurred in 21 pts (41%); most were mild and none led to treatment interruption/withdrawal. AE rate was 1200.3/100 patient-years (PY) (909.3/100 PY excluding ISRs). The most common AEs were viral upper respiratory tract infection (13; 25.5%), neutropenia (13; 25.5%), and cough (12; 23.5%). Nine serious AEs occurred in 7 pts (13.7%; 19.3/100 PY); 5 were infections, all in the <30 kg group. Two deaths occurred, both in the <30 kg group. Median Juvenile Arthritis Disease Activity Score-71 improved (decreased) from baseline to week 52 for TCZ-naive pts (<30 kg, –13.9; ≥30 kg, –12.4) and was maintained or improved further for pts who switched from TCZ IV (<30 kg, –0.7; ≥30 kg –0.2).

Abstract OP0103 – Table 1

Conclusions A PK-based strategy successfully bridged TCZ SC to TCZ IV in pts with sJIA. Dosing regimens of 162 mg Q2W in pts<30 kg and 162 mg QW in pts≥30 kg provided adequate exposure to support efficacy comparable to that of TCZ IV. Except for ISRs, safety was consistent with the known safety profile of TCZ IV in sJIA.

Reference [1] De Benedetti F, et al. N Engl J Med2012;367:2385–2395.

Disclosure of Interest H. Brunner: None declared, N. Ruperto Consultant for: AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Biogenidec, Boehringer, BMS, Celgene, CrescendoBio, EMD, Speakers bureau: AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Biogenidec, Boehringer, BMS, Celgene, CrescendoBio, EMD, D. Lovell Grant/research support from: National Institutes of Health, NIAMS, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson and Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Janssen, Speakers bureau: Genentech, I. Calvo-Penedes: None declared, G. Horneff: None declared, M. L. Gamir Gamir: None declared, M. Hufnagel: None declared, J. Hsu Employee of: Roche, M. Bao Employee of: Roche, W. Douglass Employee of: Roche, N. L. Mallalieu Employee of: Roche, C. Wells Shareholder of: Roche, Employee of: Roche, C. M. Mela Employee of: Roche, F. De Benedetti Grant/research support from: Novartis, Roche, Pfizer, SOBI, AbbVie, Novimmune, BMS, Sanofi

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