Session Information
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
A Phase 3b, open-label,
multicenter study (CLIPPER; NCT00962741) demonstrated the efficacy of
etanercept (ETN) in subjects with the extended oligoarticular (eo),
enthesitis-related (ERA), and psoriatic (PsA) subtypes of juvenile idiopathic
arthritis (JIA). The objective of the extension study (CLIPPER2; NCT01421069) was
to assess the safety and clinical benefit of ETN in pediatric subjects with
these JIA subtypes in the long term (8 years).
Methods:
127 subjects with eoJIA (2–17
yrs), ERA (12–17 yrs), or PsA (12–17 yrs) who had ≥1 dose of ETN (0.8
mg/kg QW [max. 50 mg]) and who participated for ~24 months in CLIPPER were
eligible for CLIPPER2. Efficacy endpoints included the proportions of subjects
achieving JIA ACR 30/50/70/90/100 and Wallace/JADAS inactive disease responses and
standard measures of disease activity. Safety, including malignancy and other treatment-emergent
adverse events (TEAEs) and serious TEAEs, was assessed from baseline of CLIPPER
to month 48.
Results:
109/127 (86%) subjects (eoJIA
n=55, ERA n=31, PsA n=23) entered CLIPPER2. Improvements from baseline in
disease activity (table 1) and proportions of subjects achieving JIA ACR
30/50/70/90/100 and inactive disease responses (figure) at months 24 were
largely maintained at months 48. Safety results are summarized in table 2. All
23 serious TEAEs occurred at a rate of ≤2 events each. Most frequently
reported TEAEs were (number of events [N], events per patient yr [EPPY]):
headache (27, 0.061), arthralgia (15, 0.034), pyrexia (14, 0.032), diarrhea
(12, 0.027), and leukopenia (10, 0.023). Most commonly reported treatment-emergent
(TE) infections were (N, EPPY): upper respiratory tract infection (115, 0.260),
pharyngitis (73, 0.165), gastroenteritis (29, 0.066), and bronchitis (24,
0.054). TEAEs and TE infections were less frequent in months 36–48 (N, (EPPY)):
48 (0.596), 54 (0.670) than in months 0–12: 193 (1.738), 248 (2.233). One case
of malignancy (Hodgkin’s disease) was reported in an eoJIA subject who was treated
with ETN for 27 months and methotrexate ~8 years prior to onset. No cases of
active tuberculosis, demyelinating disorders, or deaths were reported.
Conclusion:
Open-label ETN treatment up
to 48 months was well-tolerated and effective in treating subjects with JIA
subtypes. AEs were fewer in months 36–48 versus months 0–12.
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Table 1. Disease Characteristics for all JIA Subtypes. |
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|
Measure |
CLIPPER |
CLIPPER2 |
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|
Mean (95% CI) |
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|
Baseline (n = 127)* |
Month 3 (n = 123)* |
Month 24 (n = 109)* |
Month 36 (n = 87)* |
Month 42 (n = 73)* |
Month 48 (n = 64)* |
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|
PtGA |
4.96 (4.6, 5.4) |
2.21 (1.9, 2.5) |
0.97 (0.7, 1.2) |
1.16 (0.8, 1.5) n = 85 |
1.10 (0.7, 1.5) n = 69 |
1.32 (0.9, 1.8) |
|
|
PGA |
5.02 (4.7, 5.3) |
1.50 (1.3, 1.7) |
0.62 (0.5, 0.8) n = 108 |
0.67 (0.5, 0.9) |
0.70 (0.4, 1.0) |
0.67 (0.5, 0.9) n = 63 |
|
|
CHAQ |
0.80 (0.7, 0.9) |
0.32 (0.3, 0.4) |
0.16 (0.1, 0.2) |
0.16 (0.1, 0.2) n = 62 |
0.17 (0.1, 0.3) n = 46 |
0.14 (0.0, 0.2) n = 37 |
|
|
HAQ† |
N/A |
N/A |
N/A |
0.18 (0.0, 0.3) n = 24 |
0.21 (0.1, 0.4) n = 28 |
0.14 (0.0, 0.3) n = 27 |
|
|
CRP, mg/L |
8.26 (5.7, 10.8) |
2.47 (1.2, 3.8) n = 120 |
2.76 (1.7, 3.8) n = 103 |
2.97 (1.4, 4.5) n = 82 |
3.06 (0.9, 5.2) n = 69 |
2.88 (1.6, 4.1) n = 63 |
|
|
JADAS |
17.21 (15.9, 18.5) n = 118 |
5.50 (4.7, 6.4) n = 120 |
2.28 (1.7, 2.9) n = 102 |
2.74 (1.8, 3.7) n = 64 |
2.53 (1.4, 3.7) n = 59 |
2.48 (1.8, 3.1) n = 61 |
|
|
No. active joints |
6.74 (5.9, 7.6) |
1.72 (1.3, 2.2) |
0.61 (0.2, 1.0) |
0.59 (-0.1, 1.3) n = 69 |
0.74 (0.1, 1.4) n = 68 |
0.49 (0.3, 0.7) n = 63 |
|
|
No. active joints (LOM) |
5.72 (5.0, 6.5) |
1.62 (1.2, 2.0) |
1.06 (0.5, 1.6) |
0.74 (0.1, 1.4) n = 69 |
1.16 (0.5, 1.9) n = 68 |
1.02 (0.6, 1.4) n = 63 |
|
|
Note: Month 30 data were excluded due to the number of missing data at this time point. *Number of patients are indicated when different to the column header. †No subjects were assessed with HAQ in CLIPPER PtGA, patient/parent global assessment; PGA, physician’s global assessment; CHAQ, Childhood Health Assessment Questionnaire (for subjects <18 years); HAQ Health Assessment Questionnaire (for subjects ≥18 years); CRP, C-reactive protein; JADAS, Juvenile Arthritis Disease Activity Score; LOM, limitation of motion. |
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Table 2. Safety Summary up to 48 Months (CLIPPER/CLIPPER2). |
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|
eoJIA n = 60 EXP = 211.860 N (EPPY)* |
ERA n = 38 EXP = 135.313 N (EPPY)* |
PsA n = 29 EXP = 95.321 N (EPPY)* |
Total n = 127 EXP = 442.494 N (EPPY)* |
|
TEAEs† |
197(0.930) |
138 (1.020) |
70 (0.734) |
405 (0.915) |
|
TE infections |
304 (1.435) |
83 (0.613) |
96 (1.007) |
483 (1.092) |
|
TE ISRs |
23 (0.109) |
29 (0.214) |
12 (0.126) |
64 (0.145) |
|
TEAEs causing withdrawal† n (%) |
1 (0.005) |
7 (0.052) |
0 |
8 (0.018) |
|
TE infections causing withdrawal, n (%) |
2 (0.009) |
0 |
1 (0.010) |
3 (0.007) |
|
Serious TEAEs† |
4 (0.019) |
15 (0.111) |
4 (0.042) |
23 (0.052) |
|
Serious TE infections |
5 (0.024) |
4 (0.030) |
3 (0.031) |
12 (0.027) |
|
Opportunistic infections‡ |
0 |
1 (0.007) |
1 (0.010) |
2 (0.005) |
|
Infections considered preventable by vaccination in subjects not previously vaccinated |
7 (0.033) |
1 (0.007) |
1 (0.010) |
9(0.020) |
|
Infections considered preventable by vaccination in subjects previously vaccinated |
1 (0.005)µ |
0 |
0 |
1 (0.002) |
|
TE autoimmune disorders# |
1 (0.005) |
3 (0.022) |
1 (0.010) |
5 (0.011) |
|
*All values are reported as number of events (N) per patient-year (EPPY) of exposure (EXP) to ETN, unless otherwise stated. Year 1: Up to month 12 in CLIPPER; Year 2: from month 12 to month 24 in CLIPPER or baseline in CLIPPER2; Year 3 onwards: calendar years. †Excluding infections and injection site reactions (ISRs). ‡Two cases of herpes zoster affecting two dermatomes (ERA) and one dermatome (PsA) were considered to be opportunistic infections and one case of latent tuberculosis (purified protein derivative conversion) was not considered to be an opportunistic infection. µOne case of rubella. #Two cases of uveitis, two cases of iridocyclitis, and one case of Crohn’s disease were TE and one case of Crohn’s disease was not. |
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To cite this abstract in AMA style:
Ruperto N, Constantin T, Foeldvari I, Vojinovic J, Horneff G, Burgos-Vargas R, Nikishina I, Akikusa J, Avcin T, Chaitow J, Koskova E, Lauwerys BR, Calvo-Penedes I, Flato B, Gamir Gamir ML, Huppertz HI, Jaller Raad JJ, Jarosova K, Anton J, Macku M, Otero Escalante WJ, Rutkowska-Sak L, Trauzeddel R, Wouters C, Pedersen R, Kotak S, Bukowski JF, Hinnershitz T, Vlahos B, Martini A. An Open-Label Extension Study to Assess the Long-Term Safety and Clinical Benefit of Etanercept on Children and Adolescents with Extended Oligoarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, or Psoriatic Arthritis: A 4-Year Update [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/an-open-label-extension-study-to-assess-the-long-term-safety-and-clinical-benefit-of-etanercept-on-children-and-adolescents-with-extended-oligoarticular-juvenile-idiopathic-arthritis-enthesitis-relat/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/an-open-label-extension-study-to-assess-the-long-term-safety-and-clinical-benefit-of-etanercept-on-children-and-adolescents-with-extended-oligoarticular-juvenile-idiopathic-arthritis-enthesitis-relat/