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SAT0438 Catch-Up Growth During Tocilizumab Therapy for Systemic Juvenile Idiopathic Arthritis: 2-Year Data from a Phase 3 Clinical Trial
  1. F. De Benedetti1,
  2. N. Ruperto2,
  3. G. Espada2,
  4. V. Gerloni2,
  5. B. Flato3,
  6. G. Horneff2,
  7. B. Myones4,
  8. K. Onel4,
  9. J. Frane5,
  10. J. Wang6,
  11. T. Lipman7,
  12. K. Bharucha8,
  13. A. Martini2,
  14. D. Lovell4
  1. 1IRCCS Ospedale Pediatrico Bambino Gesu, Rome
  2. 2PRINTO, Genoa, Italy
  3. 3OUS, Oslo, Norway
  4. 4PRCSG, Cincinnati
  5. 5Consultant, Santa Monica, United States
  6. 6Roche, Welwyn, United Kingdom
  7. 7U Penn School of Nursing, Philadelphia
  8. 8Genentech, S San Francisco, United States

Abstract

Background Systemic juvenile idiopathic arthritis (sJIA), characterised by chronic arthritis associated with prominent systemic features, has a significant impact on the growing skeleton, resulting in impaired linear growth and systemic osteoporosis. A phase 3 trial (TENDER) demonstrated that the interleukin-6 (IL-6) receptor inhibitor tocilizumab (TCZ) is effective in the treatment of patients with sJIA. Long-term growth responses for children in the TENDER trial (up to week 104) are presented.

Methods The TENDER trial enrolled 112 patients (ages 2-17 years) with active, refractory sJIA (≥6-month duration with inadequate response to previous non-steroidal anti-inflammatory drugs and oral corticosteroids). After a 12-week, randomised, placebo-controlled phase, patients received open-label TCZ in the long-term extension. Height parameters, laboratory data and clinical assessments of disease activity were compared at baseline and through year 2 of the study in patients who never received growth hormone.

Results At enrolment in the TENDER trial, the height measurements of study patients revealed profound growth failure (mean WHO height standard deviation score [SDS] of –2.0; n = 103). During treatment, the majority of patients had greater than normal height velocities, with 84% of female patients and 72% of male patients demonstrating catch-up growth (Figure). The height SDS increased significantly from baseline to year 2 of the study, with a mean improvement of 0.56 (p < 0.0001, paired t-test). Additional growth analysis was performed for patients with Tanner stage <4 at baseline. Although the mean corticosteroid dose was higher in the first year (0.14 mg/kg/day compared with 0.05 mg/kg/day in the second year), mean height velocities in the first and second years of the study were comparable at 6.7 and 7.1 cm/y, respectively. During TCZ treatment, a significant increase in insulin-like growth factor 1 (IGF-1) levels was observed, suggesting a normalisation of growth hormone axis function (mean baseline IGF-1 SDS of –0.9 [n = 70] compared with year 2 mean IGF-1 SDS of –0.2 [n = 56]; p = 0.0015, paired t-test on n = 56). The osteocalcin/c-telopeptide of type 1 collagen (OC/CTX-1) ratio increased significantly (p = 0.0082, paired t-test), suggesting an increase in osteoblast activity relative to osteoclast activity. At year 1, JADAS-71 score correlated with height velocity during that year (Spearman rank r = –0.36, p = 0.0010; [n = 81]).

Conclusions TCZ therapy for sJIA resulted in catch-up growth of study patients. Additionally, TCZ therapy resulted in increased IGF-1 levels and OC/CTX-1 ratios, suggesting beneficial effects on the growth hormone axis and on bone metabolism. Improvement in JADAS scores correlated with increased height velocity. Continued data collection (for a total of 5 years) will allow a comprehensive analysis of growth outcomes in the TENDER study.

Disclosure of Interest F. De Benedetti Grant/research support from: Abbott, Pfizer, BMS, Roche, Novimmune, Novartis, SOBI, N. Ruperto Grant/research support from: Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Consultant for: (to institution) Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Speakers bureau: Abbott, Boehringer, BMS, Novartis, Astellas, Italfarmaco, MedImmune, Pfizer, Roche, G. Espada: None Declared, V. Gerloni: None Declared, B. Flato: None Declared, G. Horneff Grant/research support from: Abbott, Pfizer, B. Myones: None Declared, K. Onel Grant/research support from: Merck, Roche, J. Frane Consultant for: Genentech, J. Wang Employee of: Roche, T. Lipman Consultant for: Roche, K. Bharucha Employee of: Genentech, a member of the Roche group, A. Martini Grant/research support from: Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Consultant for: (to institution) Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Speakers bureau: Abbott, Boehringer, BMS, Novartis, Astellas, Italfarmaco, MedImmune, Pfizer, Roche, D. Lovell Grant/research support from: Natioinal Institutes of Health, Consultant for: AstraZeneca, Centocor, Wyeth, Amgen, BMS, Abbott, Pfizer, Roche, Novartis, UCB, Forest Research

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