SAT0438 Catch-Up Growth During Tocilizumab Therapy for Systemic Juvenile Idiopathic Arthritis: 2-Year Data from a Phase 3 Clinical Trial
Authors: F. De Benedetti, N. Ruperto, G. Espada, V. Gerloni, B. Flato, G. Horneff, B. Myones, K. Onel, J. Frane, J. Wang, T. Lipman, K. Bharucha, A. Martini, D. Lovell
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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 (<i>p</i> &lt; 0.0001, paired <i>t</i>-test). Additional growth analysis was performed for patients with Tanner stage &lt;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]; <i>p</i> = 0.0015, paired <i>t</i>-test on n = 56). The osteocalcin/c-telopeptide of type 1 collagen (OC/CTX-1) ratio increased significantly (<i>p</i> = 0.0082, paired <i>t</i>-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 <i>r</i> = –0.36, <i>p</i> = 0.0010; [n = 81]). <h3>Image/graph</h3> <h3>Conclusions</h3> 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. <h3>Disclosure of Interest</h3> 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