ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2855

Subcutaneous Abatacept in Patients Aged 2–17 Years with Polyarticular Juvenile Idiopathic Arthritis and Inadequate Response to Biologic or Non-Biologic Disease-Modifying Antirheumatic Drugs: Pharmacokinetics, Effectiveness, Safety and Immunogenicity over 2 Years

Hermine I. Brunner1, N Ruperto2, G Vega-Cornejo3, A Berman4, Inmaculada Calvo5, R Cuttica6, F Ávila-Zapata7, Michael Henrickson1, DJ Kingsbury8, D Viola9, V Keltsev10, K Minden11, John F. Bohnsack12, X Li13, M Nys14, R Wong13, S Banerjee13, Daniel J Lovell1 and Alberto Martini15, 1Cincinnati Children’s Hosp. Medical Center, Cincinnati, OH, 2Istituto G. Gaslini Pediatria II Reumatologia, Genoa, Italy, 3Clinica de Reumatología y Enfermedades Autoinmunes (CREA), Hospital México Americano, Guadalajara Jalisco, Mexico, 4Universidad Nacional de Tucuman and Centro Médico Privado de Reumatología, Tucuman, Argentina, 5Hospital Univ. La Fe, Valencia, Spain, 6Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina, 7Star Medica Hospital, Yucatán, Mexico, 8Randall Children’s Hospital at Legacy Emanuel, Portland, OR, 9CAICI Institute, Rosario City, Santa Fe State, Argentina, 10GBUZ Samara region "Togliatti City Clinical Hospital No.5" Rheumatology Department, Togliatti, Russian Federation, 11German Rheumatism Research Center and Charité University Medicine, Berlin, Germany, 12University of Utah School of Medicine, Salt Lake City, UT, 13Bristol-Myers Squibb, Princeton, NJ, 14Bristol-Myers Squibb, Braine-l’Alleud, Belgium, 15Istituto G. Gaslini Pediatria II Reumatologia and University of Genova, Genoa, Italy

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: , , ,

Session Information

Date: Tuesday, November 7, 2017

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

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: IV abatacept (ABA) 10 mg/kg every 4 weeks is well tolerated and effective in reducing the signs and symptoms of polyarticular juvenile idiopathic arthritis (pJIA) in patients (pts) aged 6–17 years (y).1 The objective of this study was to investigate the pharmacokinetics (PK), effectiveness, safety and immunogenicity (IMG) of SC ABA in pts with active pJIA aged 2–17 y over a 2-y period. Methods: Pts with pJIA and an inadequate response/intolerance to ≥1 DMARD were enrolled into this 2-y, single-arm, open-label, Phase III study (NCT01844518) and grouped into 2–5-y and 6–17-y cohorts. Pts received SC ABA weekly for 4 months (M) based on body-weight tier (10–<25 kg [50 mg]; 25–<50 kg [87.5 mg]; ≥50 kg [125 mg]). JIA-ACR criteria 30 (JIA-ACR30; ACR Pediatric 30) responders at 4 M could receive abatacept for another 20 M. Primary endpoint was ABA steady-state serum trough concentration (Cminss) at 4 M in pts aged 6–17-y at enrollment. Other endpoints included PK, JIA-ACR30, 50, 70 and 90, inactive disease (no active joints, Physician Global Assessment of disease activity ≤10 mm, CRP ≤0.6 mg/dL) response rates, safety and IMG over time. Results: For the 2–5-y and 6–17-y cohorts, baseline characteristics and cumulative drug exposure for 2-y period are shown in Table 1. Overall, the number of pts completed, discontinued (D/C) and ongoing in the cumulative 2-y period in the 2–5-y cohort were: 24 (52.2%), 7 (15.2%) and 15 (32.6%); in the 6–17-y cohort: 132 (76.3%), 36 (20.8%) and 0. D/C due to lack of efficacy were 5 (10.9%) and 17 (9.8%) in the 2–5-y and 6–17-y cohorts, respectively. Target ABA Cminss (>10 µg/mL) was achieved at 4 M and was comparable across weight-tiered dose groups and age cohorts. Pts responded early to ABA and showed robust JIA-ACR30, 50, 70 and 90, and inactive disease responses over time (Figure). No new or unexpected safety events were reported (Table 2). IMG response was low: 4 (8.7%) 2–5-y and 4 (2.3%) 6–17-y pts while on treatment.

Conclusion: In this analysis of pts with pJIA aged 2–17 y during the cumulative 2-y period, SC abatacept was well tolerated and demonstrated robust efficacy and targeted PK with no new safety concerns.

1. Ruperto N, et al. Lancet 2008;372:383–91.

 


Table 1. Demographics, Disease Characteristics and Concomitant Medication at Baseline and Study Drug Exposure
Characteristic Patients aged 2–5 years (n=46) Patients aged 6–17 years (n=173)
Age, years 4.0 (3.0, 5.0) 13.0 (10.0, 15.0)
Female, n (%) 28 (60.9) 136 (78.6)
Weight, kg 18.0 (15.0, 21.1) 45.0 (31.5, 57.0)
Number of active joints

7.0 (6.0, 12.0)

10.0 (6.0, 19.0)

JIA disease onset, n (%) Polyarthritis RF-negative Polyarthritis RF-positive Extended oligoarthritis Systemic arthritis Psoriatic arthritis Enthesitis-related arthritis Other   29 (63.0) 3 (6.5) 10 (21.7) 0 4 (8.7) 0 0   94 (54.3) 46 (26.6) 19 (11.0) 5 (2.9) 0 4 (2.3) 5 (2.9)*
Oral corticosteroid use, n (%) 9 (19.6) 56 (32.4)
Oral corticosteroid dose, mg/day† 3.1 (2.5, 6.3)‡ 5.0 (3.4, 5.6)§
Concomitant MTX use, n (%) 37 (80.4) 136 (78.6)
MTX dose, mg/m2/week 13.3 (10.9, 15.3) 11.6 (9.7, 14.4)
Route of MTX administration, n (%) Oral SC IM Parenteral     18 (39.1) 19 (41.3) 0 0     76 (43.9) 51 (29.5) 8 (4.6) 1 (0.6)
Prior biologic use, n (%) 10 (21.7) 46 (26.6)
Abatacept exposure, months, mean (SD) 18.8 (7.3) 21.8 (6.9)
Values represent median (25th percentile, 75th percentile), unless otherwise specified *Protocol deviation: persistent oligoarthritis (n=4), undifferentiated (n=1) †Prednisone equivalent ‡n=8 §n=52 Including etanercept, adalimumab, tocilizumab JIA=juvenile idiopathic arthritis


 

Table 2. Summary of AEs Over 2 Years (All Treated Patients)
Event Patients aged 2–5 years (n=46) Patients aged 6–17 years (n=173)
Deaths 0 0
SAEs* 3 (6.5) 14 (8.1)
Related SAEs† 1 (2.2) 1 (0.6)
Discontinued due to SAEs‡ 0 4 (2.3)
AEs 43 (93.5) 152 (87.9)
Related AEs 27 (58.7) 54 (31.2)
Discontinued due to AEs 1 (2.2) 7 (4.0)
AEs of special interest§    
Malignancies 0 1 (0.6)
Autoimmune disorders** 0 3 (1.7)
Local injection-site reactions 2 (4.3) 12 (6.9)
Infections 36 (78.3) 118 (68.2)
Data are n (%)

*2–5-year cohort: overdose, tendon disorder, febrile convulsion (each n=1, 2.2%);
6–17-year cohort: sepsis, abdominal pain, and upper respiratory tract infection (occurred in one patient), appendicitis, pneumonia, pyelonephritis, concussion, radius fracture, urinary calculus, nephrolithiasis, anemia, vertigo, chest pain, synovitis, hypomagnesemia and ovarian germ cell teratoma stage III (occurred in one patient), autonomic nervous system imbalance †2–5-year cohort: overdose; 6–17-year cohort: sepsis ‡6–17-year cohort: sepsis, vertigo, ovarian germ cell teratoma stage III, autonomic nervous system imbalance §No opportunistic infections related to study drug occurred during the study in either cohort 6–17-year cohort: ovarian germ cell teratoma stage III **6–17-year cohort: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), psoriasis, Takayasu’s arteritis SAE=serious adverse event


 
Disclosure: H. I. Brunner, Novartis, Genentech, Pfizer, UCB, Lilly, Jannsen, Ablynx, AbbVie, BMS, EMD Serono, AstraZeneca, 5; N. Ruperto, The G. Gaslini Hospital, BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi, 2,AbbVie, Ablynx, Amgen, AstraZeneca, Baxalta Biosimilars, Biogenidec, Boehringer, Bristol Myers Squibb, Celgene, Eli-Lilly, EMD Serono, Hoffman-La Roche, Janssen, Novartis, Pfizer,, R-Pharm, Sanofi, Servier, Sinergie, Takeda, 8,AbbVie, Ablynx, Amgen, AstraZeneca, Baxalta Biosimilars, Biogenidec, Boehringer, Bristol Myers Squibb, Celgene, Eli-Lilly, EMD Serono, Hoffman-La Roche, Janssen, Novartis, Pfizer,, R-Pharm, Sanofi, Servier, Sinergie, Takeda, 5; G. Vega-Cornejo, None; A. Berman, None; I. Calvo, Novartis Pharmaceutical Corporation, 2,AbbVie, Roche, Novartis, Sobi, 8; R. Cuttica, None; F. Ávila-Zapata, None; M. Henrickson, None; D. Kingsbury, None; D. Viola, None; V. Keltsev, None; K. Minden, Pfizer, Abbvie, Roche, 2,Abbvie, Pfizer, Pharm-Allergan, Roche, 5; J. F. Bohnsack, None; X. Li, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; M. Nys, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; R. Wong, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; S. Banerjee, Bristol-Myers Squibb, 1,Bristol-Myers Squibb, 3; D. J. Lovell, National Institutes of Health, NIAMS, 2,AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Janssen, 5,Genentech and Biogen IDEC Inc., 8; A. Martini, AbbVie, Boehringer, Novartis, R-Pharm, 5.

To cite this abstract in AMA style:

Brunner HI, Ruperto N, Vega-Cornejo G, Berman A, Calvo I, Cuttica R, Ávila-Zapata F, Henrickson M, Kingsbury D, Viola D, Keltsev V, Minden K, Bohnsack JF, Li X, Nys M, Wong R, Banerjee S, Lovell DJ, Martini A. Subcutaneous Abatacept in Patients Aged 2–17 Years with Polyarticular Juvenile Idiopathic Arthritis and Inadequate Response to Biologic or Non-Biologic Disease-Modifying Antirheumatic Drugs: Pharmacokinetics, Effectiveness, Safety and Immunogenicity over 2 Years [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/subcutaneous-abatacept-in-patients-aged-2-17-years-with-polyarticular-juvenile-idiopathic-arthritis-and-inadequate-response-to-biologic-or-non-biologic-disease-modifying-antirheumatic-drugs-p/. Accessed .

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