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SAT0515 GROWTH AND DEVELOPMENT OF PATIENTS WITH POLYARTICULAR-COURSE JUVENILE IDIOPATHIC ARTHRITIS TREATED WITH SUBCUTANEOUS ABATACEPT
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  1. Nicolino Ruperto1,
  2. Hermine Brunner2,
  3. Gabriel Vega Cornejo1,
  4. Alberto Berman3,
  5. Jordi Anton1,
  6. Ruben Cuttica1,
  7. Vladimir Keltsev1,
  8. Diego Oscar Viola1,
  9. Bernard Lauwerys3,
  10. Maria Elena Rama1,
  11. John Bohnsack2,
  12. Caroline Caillaud1,
  13. Kirsten Minden1,
  14. Mahmood Moosa Ally1,
  15. Elisabeth Gervais1,
  16. Riana Van Zyl1,
  17. Yash Gandhi4,
  18. Bindu Murthy4,
  19. Marleen Nys5,
  20. Robert Wong4,
  21. Jade Hoang4,
  22. Alberto Martini1,
  23. Daniel J. Lovell2
  1. 1Istituto Gaslini, Genoa, Italy
  2. 2CHMC Cincinnati, Cincinnati, United States of America
  3. 3PRINTO, Istituto Gaslini, Genoa, Italy
  4. 4Bristol-Myers Squibb, Princeton, United States of America
  5. 5Bristol-Myers Squibb, Braine L’Alleud, Belgium

Abstract

Background Efficacy of SC abatacept (ABA) in patients (pts) with polyarticular-course juvenile idiopathic arthritis (pJIA) was shown in a 2-year, open-label, Phase III international study (NCT01844518).1 Restricted growth and delayed puberty are associated with pJIA;2 however, the effect of ABA on growth and development is unknown.

Objectives To investigate the effect of ABA on height, BMI and Tanner staging, and to assess the impact of BMI on ABA efficacy in pts with pJIA.

Methods Patients with pJIA were grouped into two age cohorts (2–5 and 6–17 years [yrs]) and received weight-tiered SC ABA (10 to <25 kg [50 mg], 25 to <50 kg [87.5 mg], ≥50 kg [125 mg]) weekly for 4 months (mths). JIA-ACR30 criteria responders at 4 mths could receive SC ABA for another 20 mths.1 Standardised height and BMI were obtained by z-score calculation with age adjustment using World Health Organization Child Growth Standards (2007); mean changes from baseline (BL) in z-scores were assessed over time to Day (D) 645. Efficacy was assessed by age cohort using linear regression (BL standardised BMI as a continuous variable) and by logistic regression with BL standardised BMI (z-score) classed as low (≤−2), normal (>−2 to ≤1), overweight (>1 to ≤2) and obese (>2) (intent-to-treat, non-responder imputation for missing efficacy data). In the 6–17-yr cohort, Tanner staging was recorded at BL and at discontinuation or completion of study.

Results Data for standardised height and BMI are presented. In 6–17-yr-old pts with BL Tanner stage ≤3 (n=100), BL mean (SD) height was −0.53 (1.53); at D645, mean (95% CI) change was 0.20 (0.06, 0.34; Figure 1). In 6–17-yr-old pts with a BL height ≤−1 (n=42), BL mean (SD) height was −2.10 (1.01) and mean (95% CI) change at D645 was 0.49 (0.23, 0.76). In 2–5-yr-old pts, BL mean (SD) height was 0.07 (1.37); at D645, mean (95% CI) change was 0.13 (−0.09, 0.36). In 13 pts aged 6–17 yrs of the lowest height (Tanner stage ≤3 and BL height ≤−2), mean (SD) height increased from −3.28 (1.10) at BL to −2.59 (1.31) by D645.

At BL, mean (SD) BMI was 0.20 (1.33) in the 6–17-yr cohort (n=173) and 0.25 (1.57) in the 2–5-yr cohort (n=46); at D645, mean (95% CI) change in BMI was 0.02 (−0.13, 0.16; Figure 2) and 0.17 (−0.08, 0.42), respectively. Overall, no relationship was seen between change from BL in Juvenile Arthritis Disease Activity Score 71 (JADAS71) and BL BMI in either age cohort. The proportions (odds ratio [OR]; 95% CI of OR) of obese pts aged 6–17 yrs achieving JIA-ACR30 (0.15; 0.04, 0.55), JIA-ACR50 (0.18; 0.05, 0.63), JIA-ACR70 (0.17; 0.04, 0.67) and JADAS71 minimal disease activity (0.27; 0.07, 1.03) at Day 645 were significantly lower compared with pts with a normal BMI, but the sample size in the obese category was low (n=12); this effect was not seen in overweight pts (n=37).

In female pts (n=92), shifts in Tanner stages from BL to D645 were as expected; male sexual maturation was difficult to assess due to the small sample size (n=20).

Conclusion Abatacept improves growth and development in pts with pJIA. Early therapeutic intervention with abatacept may help reduce growth restrictions in pts with pJIA. BMI may impact the efficacy response, resulting in lower efficacy in obese, but not in overweight, pts with pJIA versus pts with normal BMI.

References [1] Brunner HI, et al. Arthritis Rheumatol2018;70:1144–54.

[2] Umławska W, et al. Arch Med Sci2010;6:19–23.

Acknowledgement Professional medical writing: Lola Parfitt, MRes, Caudex; funding: Bristol-Myers Squibb

Disclosure of Interests Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, AbbVie, Astrazeneca-Medimmune, Biogen, Boehringer, Bristol-Myers Squibb, Eli-Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, SanofiServier, Sinergie, Sobi and Takeda., Speakers bureau: Received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, AbbVie, Astrazeneca-Medimmune, Biogen, Boehringer, Bristol-Myers Squibb, Eli-Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, SanofiServier, Sinergie, Sobi and Takeda., Hermine Brunner Grant/research support from: Bristol-Myers Squibb, Pfizer, Consultant for: Pfizer, Bristol-Myers Squibb, Janssen, Novartis, Lilly, Roche, GlaxoSmithKline, Sanofi, Speakers bureau: Novartis, Roche, Gabriel Vega Cornejo Grant/research support from: I currently have no conflicts of interest, I am only setting protocols for the pharmaceutical industry with Parexel, Sanofi and Bristol-Myers Squibb., Alberto Berman Grant/research support from: Grants/research support: Roche/Genentech, Bristol-Myers Squibb, Merck Serono, AbbVie, Amgen, Eli Lilly, Janssen, Jordi Anton Grant/research support from: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Consultant for: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Speakers bureau: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Ruben Cuttica Grant/research support from: Roche, Pfizer, Lilly, Bristol Myers Squibb, Novartis, Sanofi Aventis, UCB, Janssen., Consultant for: Roche, Pfizer, Lilly, Bristol Myers Squibb, Novartis, Sanofi Aventis, UCB, Janssen., Speakers bureau: Roche, Pfizer, Lilly, Bristol Myers Squibb, Novartis, Sanofi Aventis, UCB, Janssen., Vladimir Keltsev: None declared, Diego Oscar Viola: None declared, Bernard Lauwerys: None declared, Maria Elena Rama: None declared, John Bohnsack Grant/research support from: Grant/research support – I have participated and conducted drug trials supported by Bristol-Myers Sqibb, Pfizer, Janssen, Genentech, Roche, and AbbVie. I have received research support from Janssen. All of the support for these studies was paid to my institution, the University of Utah, and not directly to me., Consultant for: I served as a one-time consultant to Novartis on a Data Safety Monitoring Board for Regeneron., Caroline Caillaud: None declared, Kirsten Minden Consultant for: AbbVie, Mahmood Moosa Ally: None declared, Elisabeth Gervais Grant/research support from: Roche, Pfizer, Consultant for: Bristol-Myers Squibb, UCB, Riana Van Zyl: None declared, Yash Gandhi Shareholder of: Bristol-Myers Squibb, Advaxis, Employee of: Bristol-Myers Squibb, Bindu Murthy Shareholder of: Bristol-Myers Squibb, Johnson & Johnson, Employee of: Bristol-Myers Squibb, Marleen Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Jade Hoang Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Alberto Martini Consultant for: I do not have any conflict of interest to declare since starting from 1 March 2016 I became the Scientific Director of the G. Gaslini Hospital; therefore, my role does not allow me to render private consultancies resulting in personal income.

I perform consultancy activities on behalf of the Gaslini Institute for the companies listed below:

AbbVie, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, Pfizer, R-Pharm.

The money received for these activities are directly transferred to the Gaslini Institute’s bank account. Before March 2016, I was the head of the Pediatric Rheumatology Department at the G. Gaslini Hospital, where the PRINTO Coordinating Centre is located. For the coordination activity of the PRINTO network, the Gaslini Hospital received contributions from the industries listed in this section. This money has been reinvested for the research activities of the hospital in fully independent manners besides any commitment with third parties., Daniel J Lovell Consultant for: Consulting fees and/or honoraria from Astra Zeneca, Wyeth Pharma, Amgen, Abbott, Pfizer, F. Hoffmann-La Roche, Novartis, UBC, Takeda, GSK, Boehringer, and Celgene

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