Session Information
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Adalimumab (ADA) is a tumor necrosis factor (TNF) inhibitor used for treatment of chronic immune diseases. The safety of ADA treatment in pediatric patients (pts) is particularly important since prolonged treatment for these conditions is often required. The objective of this study is to evaluate the safety of ADA, alone or in combination with concomitant therapy, in pediatric pts with polyarticular juvenile idiopathic arthritis (pJIA), enthesitis-related arthritis (ERA), psoriasis (Ps), and Crohn’s disease (CD).
Methods: Safety data from 6 clinical trials and their open-label extension studies were analyzed. Pts treated for pJIA (NCT00048542, NCT00775437, and NCT00690573) and ERA (NCT01166282 [interim week-52 data]) received ADA 24 mg/m2 body surface area every other week (eow) or 20 mg eow (<30 kg) to 40 mg eow (≥30 kg). Pediatric pts treated for Ps (NCT01251614) received ADA 0.4 mg/kg (up to 20 mg) or 0.8 mg/kg (up to 40 mg) at week 0, then eow from week 1. Pediatric pts treated for CD (NCT00409682) received open-label ADA induction therapy (160 mg and 80 mg at weeks 0 and 2, respectively, if ≥40 kg; 80 mg and 40 mg if <40 kg), followed by double-blind maintenance dosing (high dose: 40 mg eow if ≥40 kg or 20 mg eow if <40 kg at week 4; low dose: 20 mg eow if ≥40 kg or 10 mg eow if <40 kg at week 4); weekly dosing was allowed for disease flare at week 12 or later; pts received high-dose eow or weekly ADA during an open-label extension (NCT00686374). Events (E) per 100 pt-years (PY) were calculated using adverse events (AEs) reported after the first ADA study dose through 70 days after the last study dose.
Results: The analysis included 577 pediatric pts, representing 1440.7 PY of ADA exposure (Table). Over 90% of pts across indications reported treatment-emergent AEs. Common AEs were headache (13.6, 46.9, and 23.4 E/100 PY for pJIA and ERA, Ps, and CD, respectively), nasopharyngitis (12.4, 58.4, and 15.2 E/100 PY, respectively), and upper respiratory tract infection (30.2, 24.7, and 14.8 E/100 PY, respectively). The rates of serious AEs (E/100 PY) were 13.5 for pts with pJIA and ERA, 7.4 for pts with Ps, and 32.2 for pts with CD. One death was reported from an accidental fall (pt with Ps). There were no reports of malignancies, demyelinating disorders, pulmonary embolism, reactivation of hepatitis B, Stevens-Johnson syndrome, or erythema multiforme.
Conclusion: The safety profile of ADA in pediatric pts with pJIA, ERA, Ps, or CD was similar across indications, and no new safety signals specific to the pediatric population were identified. Table. Treatment-Emergent Adverse Events Occurring in ≥1% of Patients in Pediatric Adalimumab Clinical Trials
| Treatment-Emergent Event |
pJIA and ERA N=274 Exposure, PYs=806.9 |
Pediatric Ps N=111 Exposure, PYs=121.5 |
Pediatric CD N=192 Exposure, PYs=512.3 |
|||
|
N (%) |
Events (Events/100 PY) |
N (%) |
Events (Events/100 PY) |
N (%) |
Events (Events/100 PY) |
|
| Any AE |
267 (97.4) |
4239 (525.3) |
100 (90.1) |
630 (518.5) |
189 (98.4) |
2902 (566.5) |
| Serious AE |
67 (24.5) |
109 (13.5) |
8 (7.2) |
9 (7.4) |
92 (47.9) |
165 (32.2) |
| AE leading to discontinuation of ADA |
24 (8.8) |
31 (3.8) |
3 (2.7) |
3 (2.5) |
61 (31.8) |
77 (15.0) |
| Severe AE |
45 (16.4) |
67 (8.3) |
17 (15.3) |
24 (19.8) |
67 (34.9) |
114 (22.3) |
| Drug-related† AE |
200 (73.0) |
1536 (190.4) |
48 (43.2) |
176 (144.9) |
115 (59.9) |
621 (121.2) |
| Infection |
224 (81.8) |
1216 (150.7) |
82 (73.9) |
205 (168.7) |
145 (75.5) |
676 (132.0) |
| Serious infection |
21 (7.7) |
22 (2.7) |
1 (0.9) |
1 (0.8) |
25 (13.0) |
34 (6.6) |
| Opportunistic infection (excluding tuberculosis and oral candidiasis) |
0 |
0 |
0 |
0 |
4 (2.1) |
4 (0.8) |
| Oral candidiasis |
2 (0.7) |
2 (0.2) |
0 |
0 |
4 (2.1) |
7 (1.4) |
| Tuberculosis |
3 (1.1) |
3 (0.4) |
2 (1.8) |
2 (1.6) |
1 (0.5) |
1 (0.2) |
| Acti ve |
1 (0.4) |
1 (0.1) |
0 |
0 |
0 |
0 |
| Latent |
2 (0.7) |
2 (0.2) |
2 (1.8) |
2 (1.6) |
1 (0.5) |
1 (0.2) |
| Parasitic infection |
3 (1.1) |
5 (0.6) |
0 |
0 |
1 (0.5) |
1 (0.2) |
| Allergic reaction‡,§ |
41 (15.0) |
62 (7.7) |
7 (6.3) |
9 (7.4) |
19 (9.9) |
25 (4.9) |
| Intestinal perforation |
0 |
0 |
0 |
0 |
3 (1.6) |
3 (0.6) |
| Intestinal stricture |
― |
― |
― |
― |
6 (3.1) |
6 (1.2) |
| Worsening/new onset of psoriasis‡ |
5 (1.8) |
6 (0.7) |
10 (9.0) |
11 (9.1) |
6 (3.1) |
7 (1.4) |
| Hematologic disorders|| |
10 (3.6) |
16 (2.0) |
2 (1.8) |
3 (2.5) |
27 (14.1) |
36 (7.0) |
| Liver event¶ |
5 (1.8) |
5 (0.6) |
0 |
0 |
1 (0.5) |
1 (0.2) |
| Injection site reaction‡ |
101 (36.9) |
844 (104.6) |
11 (9.9) |
17 (14.0) |
42 (21.9) |
104 (20.3) |
| ―, analyzed only in the CD population; ADA, adalimumab; AE, adverse event; CD, Crohn’s disease; ERA, enthesitis-related arthritis; pJIA, polyarticular juvenile idiopathic arthritis; Ps, psoriasis; PYs, patient-years. *The ERA study includes interim week-52 data. †Investigator assessed as possibly or probably related to study drug. ‡None were serious. §Events included hypersensitivity (n=36), urticaria (n=27), asthma (n=16), eye pruritus (n=3), rash (n=3), bronchospasm (n=2), generalized pruritus (n=2), injection site urticaria (n=2), drug hypersensitivity (n=1), eyelid edema (n=1), generalized rash (n=1), and wheezing (n=1). One event of anaphylactic reaction was reported as an immune system disorder. ||Events included anemia (n=24), leukopenia (n=17), neutropenia (n=10), lymphopenia (n=1), macrocytic anemia (n=1), microcytic anemia (n=1), and pancytopenia (n=1); 10 events were serious (leukopenia, n=2 and neutropenia, n=2 [JIA]; anemia, n=6 [CD]). ¶Events included liver disorder (n=3), hepatotoxicity (n=1), and hepatocellular injury (n=1) in the pJIA and ERA group, and 1 serious event of hepatitis in the CD group. | ||||||
To cite this abstract in AMA style:
Horneff G, Seyger MMB, Arikan D, Kalabic J, Anderson JK, Lazar A, Williams DA, Wang C, Tarzynski-Potempa R, Hyams JS. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn’s Disease [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/safety-of-adalimumab-in-pediatric-patients-with-polyarticular-juvenile-idiopathic-arthritis-enthesitis-related-arthritis-psoriasis-and-crohns-disease/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-of-adalimumab-in-pediatric-patients-with-polyarticular-juvenile-idiopathic-arthritis-enthesitis-related-arthritis-psoriasis-and-crohns-disease/