Background/Purpose: Adalimumab (ADA) is approved for use in moderate to severe JIA in patients (pts) ≥4 yrs old in the US, EU,and Japan. ADA has not been studied in pts <4 yrs old, and limited data are available in pts ≥4 yrs old weighing <15 kg. The primary objective of this study was to assess the safety of ADA in pts 2 to <4 yrs old or ≥4 yrs old weighing <15 kg with moderately to severely active polyarticular onset/polyarticular course JIA. The secondary objectives were to evaluate the pharmacokinetics (PK) and clinical effectiveness of ADA in these pts.

Methods: This is an interim analysis of the multicenter, open-label, phase 3b ADA study in pts 2 to <4 yrs old or ≥4 yrs weighing <15 kg with moderately to severely active JIA in the US and EU. ADA was given subcutaneously every other wk, 24 mg/m² BSA up to 20 mg/dose, for a minimum of 24 wks and continued until pts reached 4 yrs old and weighed 15 kg. Concomitant methotrexate use was allowed. Adverse events (AE) were collected throughout the treatment period and include safety data up to 96 wks. Serum trough concentrations of ADA were determined for each subject using validated methods. Key effectiveness endpoints were the proportion of pts achieving PedACR30/50/70/90 at wk 24. Other outcomes included tender joint count (TJC), swollen joint count (SJC), Pain on Passive Motion (POM75), Limitation on Passive Motion (LOM69), Active Joint Count (AJC73), Child Health Assessment Questionnaire (DICHAQ), and Physician’s and Parent’s Global Assessment of Disease (PhGA and PaGA).

Results: 88% of the pts were female. At baseline, mean age=3 yrs, mean weight=13 kg, mean duration of JIA=12 months, and 39% had elevated CRP (≥0.9 mg/dL). AE incidence rates through 96 wks included: any AEs (84%, 27/32), serious AEs (16%, 5/32), infectious AEs (69%, 22/32), and serious infections (9%, 3/32). No deaths, malignancies, opportunistic infections/TB, congestive heart failure, demyelinating disease, allergic reactions, lupus-like syndrome, or blood dyscrasias were reported. The mean serum ADA trough concentrations achieved a steady-state of 7 – 8 µg/mL at weeks 12 and 24 (n=15). Of 32 pts enrolled, 31 completed 24 wks of ADA treatment; 90% achieved PedACR30 and 70% achieved PedACR70 (Table 1).

 

Table 1. PedACR Response at Week 24
	Response Ratea N=30	Response Rateb N=32
PedACR30, n (%)	27 (90.0)	27 (84.4)
PedACR50, n (%)	25 (83.3)	25 (78.1)
PedACR70, n (%)	22 (73.3)	22 (68.8)
PedACR90, n (%)	11 (36.7)	11 (34.4)
aObserved. bNonresponder imputation.

Improvements in other JIA outcomes were also seen at wk 24 of ADA treatment (Table 2). 

 

Table 2. JIA Outcomes at Week 24a
	Mean Change (SD) from Baseline
Tender Joint count (TJC75)b	-3.0 (5.5)
Swollen Joint Count (SJC66)b	-6.3 (5.8)
Pain on Passive Motion (POM75)b	-3.9 (7.3)
Limitation on Passive Motion (LOM69)b	-5.6 (5.6)
Active Joint Count (AJC73)b	-7.0 (5.7)
Child Health Assessment Questionnaire (DICHAQ)b	-0.5 (0.7)
PhGA of Disease Activityb (VAS 0–100 mm)	-45.3 (21.3)
PaGA of Disease Activityb (VAS 0–100 mm)	-32.2 (29.7)
PaGA of Painb (VAS 0–100 mm)	-29.5 (28.3)
CRPc (mg/dL)	-0.2 (3.2)
aObserved data. bn=30; cn=28.

Conclusion: The safety profile, PK, and effectiveness of ADA were similar to that seen in older pediatric patients with JIA, demonstrating that ADA is also safe and effective in younger patients 2 to <4 years old or ≥4 yrs old weighing <15 kg with active polyarticular JIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-efficacy-of-adalimumab-in-children-with-active-polyarticular-juvenile-idiopathic-arthritis-aged-2-to/