ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 948

Subcutaneous Abatacept in Patients with Polyarticular-Course Juvenile Idiopathic Arthritis and Inadequate Response to Biologic or Non-Biologic Disease-Modifying Antirheumatic Drugs: Pharmacokinetics, Efficacy and Safety

DJ Lovell1, N Ruperto2, N Tzaribachev3, G Vega-Cornejo4, I Louw5, A Berman6,7, I Calvo8, R Cuttica9, G Horneff10, F Avila-Zapata11, J Anton12, R Cimaz13, E Solau-Gervais14, R Joos15, G Espada16, X Li17, M Nys18, R Wong17, S Banerjee17, Hermine I. Brunner19, A Martini20 and For Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology Collaborative Study Group (PRCSG), 1Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2Istituto G. Gaslini Pediatria II Reumatologia, Genoa, Italy, 3Pediatric Rheumatology, Bad Bramstedt, Germany, 4Clinica de Rheumatología y Enfermedades Autoinmunes (CREA), Hospital México Americano, Guadalajara Jalisco, Mexico, 5Panorama Medical Centre, Cape Town, South Africa, 6Universidad Nacional de Tucuman and Centro Médico Privado de Reumatología, Tucumán, Argentina, 7Universidad Nacional de Tucuman and Centro Médico Privado de Reumatología, Tucuman, Argentina, 8Hospital Univ. La Fe, Valencia, Spain, 9Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina, 10Centre Paediatric Rheumatology, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany, 11Star Medica Hospital, Merida, Mexico, 12Unitat de Reumatologia Pediàtrica, Hospital Sant Joan de Déu, Barcelona, Spain, 13Pediatrics, Ospedale Pediatrico Anna Meyer, Florence, Italy, 14Hôpital de la Miletrie, Poitiers, France, 15University Hospital Gent, Gent, Belgium, 16Cramer 1853 4°C, Hospital de Ninos Dr Ricardo Gutierrez, Buenos Aires, Argentina, 17Bristol-Myers Squibb, Princeton, NJ, 18Bristol-Myers Squibb, Braine-l’Alleud, Belgium, 19Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 20Istituto G. Gaslini Pediatria II Reumatologia and University of Genova, Genoa, Italy

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , , ,

Session Information

Date: Sunday, November 13, 2016

Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects I: Juvenile Arthritis

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: IV abatacept (ABA) 10 mg/kg every 4 weeks was well tolerated and effective in reducing the signs and symptoms of polyarticular-course juvenile idiopathic arthritis (pJIA) in patients aged 6–17 years (yrs).1 SC ABA 125 mg weekly has equivalent therapeutic efficacy and comparable safety to IV ABA in adult patients with RA. Here we assessed SC ABA treatment in patients with active pJIA aged 2–17 yrs.

Methods: Two age cohorts (2–5 and 6–17 yrs) of patients with pJIA with an inadequate response/intolerance to ≥1 DMARD were enrolled in this single-arm, open-label (OL), Phase III pharmacokinetic study (NCT01844518) and received OL SC ABA weekly for 4 months (M) based on body weight tier (10–<25 kg [50 mg ABA]; 25–50 kg [87.5 mg ABA]; >50 kg [125 mg ABA]). JIA-ACR criteria 30 (JIA-ACR30; ACR Pediatric 30) responders at 4M could receive ABA for another 20M. Primary endpoint was ABA steady-state blood trough concentration (Cminss) at 4M in the 6–17-yr cohort.

Results: Patients were aged 2–5 yrs (n=32; interim analysis) or 6–17 yrs (n=173; complete 4M/interim 20M analysis; Table 1). Mean (SD) drug exposure duration was 9.8 (4.12) and 11.7 (4.33) M in the 2–5- and 6–17-yr cohorts, respectively (latter comparable to IV ABA exposure)1. The target therapeutic Cminss of 10 µg/mL at 4M was achieved in the 2–5-yr cohort (mean [SD] Cminss: 50.1 [14.2] µg/mL) and the 6–17-yr cohort2 (42.1 [14.7] µg/mL; Figure). Robust JIA-ACR30/70 and inactive disease (no active joints, physician’s global assessment of disease activity <10 mm, CRP <0.6 mg/dL) responses, respectively, were seen at 4M in the 2–5-yr cohort: 86.7, 70.0 and 51.7%, and in the 6–17-yr cohort:2 80.9, 52.6 and 29.5%. Safety data are presented in Table 2; no laboratory abnormalities or unexpected safety concerns were reported. Immunogenic responses (anti-drug antibodies) were seen in 3/31 (0 persistent [≥2 consecutive visits]) and in 3/171 (2 [1.2%] persistent) patients in the 2–5- and 6–17-yr cohorts, respectively.

Conclusion: The target therapeutic exposure for SC abatacept of Cminss of 10 µg/mL was achieved, and exceeded, in patients with pJIA aged 2–17 yrs (observed>predicted values), with marked improvements in JIA-ACR responses and no new safety concerns compared with that observed in adults or with IV abatacept in pJIA.   1. Ruperto N, et al. Lancet 2008;372:383–91. 2. Ruperto N, et al. Ann Rheum Dis 2016;75 (Suppl): 138.    

Table 1. Baseline demographics and disease characteristics
  Patients aged 2–5 years (n=32) Patients aged 6–17 years (n=173)
Age, years 5.0 (2.0, 5.0) 13.0 (6.0, 17.0)
Female, n (%) 19 (59.4) 136 (78.6)
Weight, kg 18.6 (13.3, 25.4) 45.0 (16.0, 146.3)
Number of active joints 7.0 (2.0, 27.0) 10.0 (2.0, 42.0)
MTX use, n (%) 27 (84.4) 136 (78.6)
MTX dose, mg/m2/week 13.3 (6.8, 17.7) 11.6 (1.6, 24.5)
MTX dose, mg/week 10.0 (5.0, 15.0) 15.0 (2.1, 30.0)
JIA disease onset, n (%)    
Polyarthritis RF– 22 (68.8) 94 (54.3)
Polyarthritis RF+ 3 (9.4) 43 (24.9)
Extended oligoarthritis 4 (12.5) 18 (10.4)
Persistent oligoarthritis* 1 (3.1) 5 (2.9)
Systemic arthritis 0 5 (2.9)
Other† 1 (3.1) 4 (2.3)
Enthesitis-related arthritis 0 3 (1.7)
Undifferentiated arthritis 0 1 (0.6)
Psoriatic arthritis 1 (3.1) 0
Data represent median (min, max) unless otherwise specified *Protocol deviation †2–5 years: diagnosed with disease category ‘Other’ and presented with mild intensity for all six JIA core set components; 6–17 years: misclassified polyarticular, RF negative (n=3); diagnosis of sarcoid arthritis (n=1) JIA= juvenile idiopathic arthritis
     

Table 2. Summary of AEs during the combined initial 4-month and 20-month extension period (all treated patients)
AEs, n (%) Patients aged 2–5 years (n=32) Patients aged 6–17 years (n=173)
Deaths 0 0
All AEs 26 (81.3) 127 (73.4)
Related AEs 11 (34.4) 45 (26.0)
AEs leading to discontinuation 0 4 (2.3)*
SAEs 0 8 (4.6)
Related SAEs 0 1 (0.6)
SAEs leading to discontinuation 0 2 (1.2)†
AEs of special interest    
Infections‡ 22 (68.8) 90 (52.0)
Malignancies 0 1 (0.6)
Autoimmune disorders 0 3 (1.7) §
Systemic reactions related to study drug 0 2||
Local injection-site reactions 0 10 (5.8)

*Exanthema (n=1) and fatigue (n=1), both related to study drug (as well as the two SAEs leading to discontinuation)

†Sepsis (n=1), related to study drug; stage III ovarian germ cell teratoma (n=1), not related to study drug

‡The most common infections were nasopharyngitis and upper respiratory tract infections §Episcleritis (n=1), Raynaud’s phenomenon (n=1) and psoriasis (n=1)

||Nausea (n=1) and dizziness (n=1) SAE=serious adverse event

         

 

Disclosure: D. Lovell, NIH, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, 2,Genentech, 8,Novartis, UCB, Janssen, Takeda, GSK, Boehringer Ingelheim, Celgene, 5; N. Ruperto, The G. Gaslini Hospital, which is the public hospital where I work as full time public employee, has received contributions from the following industries: BMS, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Abbot, 2,AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Biogenidec, Boehringer, BMS, Celgene, CrescendoBio, EMD, Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda,, 5,AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Biogenidec, Boehringer, BMS, Celgene, CrescendoBio, EMD, Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda,, 8; N. Tzaribachev, None; G. Vega-Cornejo, None; I. Louw, None; A. Berman, None; I. Calvo, Novartis Pharmaceutical Corporation, 2,AbbVie, Roche, Novartis, Sobi, 8; R. Cuttica, None; G. Horneff, AbbVie,Pfizer, Chugai, Roche, Novartis, 8; F. Avila-Zapata, None; J. Anton, Pfizer, Novartis, 2,Pfizer, AbbVie, Novartis, Sobi, Roche, 8; R. Cimaz, None; E. Solau-Gervais, BMS, UCB, Pfizer, AbbVie, Roche, MSD, 5; R. Joos, None; G. Espada, None; X. Li, Bristol-Myers Squibb, 3; M. Nys, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; R. Wong, Bristol-Myers Squibb, 3; S. Banerjee, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; H. I. Brunner, BMS, Novartis, Genentech, Pfizer, Sanofi, Takeda, AstraZeneca, Janssen, 5,Novartis, Genentech, 8; A. Martini, The G. Gaslini Hospital, which is the public hospital where I work as full time public employee, has received contributions from the following industries: BMS, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Abbot, 2,AbbVie, Boehringer, Celgene, Crescendo Bioscience, Janssen, MedImmune, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Vertex, Servier, 5,AbbVie, Boehringer, Celgene, Crescendo Bioscience, Janssen, MedImmune, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Vertex, Servier, 8.

To cite this abstract in AMA style:

Lovell D, Ruperto N, Tzaribachev N, Vega-Cornejo G, Louw I, Berman A, Calvo I, Cuttica R, Horneff G, Avila-Zapata F, Anton J, Cimaz R, Solau-Gervais E, Joos R, Espada G, Li X, Nys M, Wong R, Banerjee S, Brunner HI, Martini A. Subcutaneous Abatacept in Patients with Polyarticular-Course Juvenile Idiopathic Arthritis and Inadequate Response to Biologic or Non-Biologic Disease-Modifying Antirheumatic Drugs: Pharmacokinetics, Efficacy and Safety [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/subcutaneous-abatacept-in-patients-with-polyarticular-course-juvenile-idiopathic-arthritis-and-inadequate-response-to-biologic-or-non-biologic-disease-modifying-antirheumatic-drugs-pharmacokinetics/. Accessed .

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