Session Information
Date: Tuesday, October 23, 2018
Title: Pediatric Rheumatology – Clinical Poster III: Juvenile Idiopathic Arthritis and Uveitis
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Long-term surveillance of biologics is particularly important in pediatric patients (pts) who may require prolonged treatment. Since 2001, the German Biologics JIA Registry (BIKER) allows follow up of an unlimited number of pts in routine clinical care. Long term safety with regard to adverse events of special interest was assessed.
Methods: BIKER was used to identify non-systemic JIA pts on biologics. Safety assessments based on adverse events (AE) reports for 25 predefined AEs of special interest (AESI) including serious and medically important infection, uveitis, chronic inflammatory bowel disease, cytopenia, hepatic event, anaphylaxis, depression, pregnancy, malignancy, and death. Events per 100 patient-years (PY) were calculated using AEs reported after first dose through 70 days after last dose. Rates were compared by Wald test.
Results: 3591 courses of biologics with a total exposure time of 6837 PY were identified with Etanercept (ETA,5015 PY) as most frequently used followed by Adalimumab (ADA,1298 PY), Tocilizumab (TOC,251 PY), Abatacept (ABA,106 PY), Infliximab (INF, 99 PY), and Golimumab (GOL,72 PY). Differences in JIA category distribution and concomitant treatment between these cohorts were noted. A total of 5155 AE (rate 75.4/100 years), 461 SAE (5.4) and 611 AESI (8.9) were reported. The most common AESI were uveitis (227) followed by medically important infections (146), cytopenias (44), hepatic events (37), other autoimmunopathies (27), chronic inflammatory bowel disease (22), depression (22), anaphylaxis (18), pregnancies (10) evolving hypertension (9) and malignancies (7). There were marked differences in the rate of AESI between the biologic-cohorts. Risk Ratios for serious infections were higher with ADA&GOL and lower with ETA. One case of latent tuberculosis infection but no further opportunistic infections were reported. RR for uveitis reports were significantly higher in all TNF-antibody cohorts and lower with ETA or TOC which presumably is biased by indication. RR for hepatic events were significantly higher in the TOC cohort and lower with ETA. RR for cyctopenias was significantly higher with TOC. RR for anaphylaxis were significantly higher in the ABA, TOC and INF cohorts probably due to the intravenous route of application. RR for inflammatory bowel disease was higher upon Infliximab which presumably is biased by indication. There was no death in this cohort.
|
Biologic |
ABA |
ADA |
ETA |
GOL |
INF |
TOC |
|
Pat/exposure years |
94/106 |
827/1298 |
2336/5015 |
67/72 |
66/95 |
201/251 |
|
AESI/rate/100PY |
11/10.3 |
173/13.3 |
340/6.8 |
16/22.3 |
24/25.3 |
47/18.7 |
|
Uveitis |
2/1,9 0.6[0.2-2.6] p=0.678 |
85/6.5 4.0[3.1-5.2] p=<0.0001 |
121/2. 0.4[0.3-0.5] p<0.0001 |
6/8.4 2.5[1.1-5.7] P=0.024 |
10/10.6 3.2[1.7-6.1] p=0.0003 |
3/1.2 0.3[0.1-1.1] P=0.071 |
|
Infection |
2/1,9 1.0[0.2-4.0] p=1.0 |
35/2.7 2.1[1.4-3.1] p=0.0001 |
95/1.9 0.7[0.5-0.9] p=0.025 |
6/8.4 4.0[1.8-9.1] P=0.0008 |
3/3.2 1.5[0.5-4.7] P=0.495 |
5/2.0 0.9[0.4-2.3] P=0.866 |
|
Cytopenia |
3/0.2 0.5[0.2-1.6] p=0.566 |
30/0.6 0.8[0.4-1.5] P=0.441 |
1/1.1 1.7[0.2-12] P= 0.62 |
10/4.0 7.7[3.9-16] P<0.0001 |
||
|
Hepatic Event |
1/0,9 2.0[0.3-14} p=0.498 |
10/0.8 2.5[1.2-5.1] p=0.014 |
19/0.4 0.4[0.2-0.7] P=0.003 |
1/1.1 2.0[0.3-14] P=0.503 |
6/2.4 5.1[2.1-12] P=0.0002 |
|
|
Autoimmune disease |
2/1,9 5.7[1.4-24] p=0.017 |
12/0.9 5.3[2.5-11] p=<0.0001 |
8/0.2 0.2[0.1-0.3] p<0.0001 |
1/1.4 3.6[0.5-26] P=0.207 |
1/1.1 2.7[0.4-20] P=0.324 |
3/1.2 3.3[1.0-11] P=0.053 |
|
IBD |
2/0.2 0.7[0.2-2.9] p=0.709 |
18/0.4 1.6[0.6-4.8] p=0.373 |
2/2.1 7.1[1.7-30] p=0.008 |
|||
|
Depression |
1/0,9 3.4[0.5-25] p=0.231 |
5/0.4 2.0[0.7-5.3] p=0,183 |
15/0.3 0.8[0.3-2.0] P=0.586 |
1/0.4 1.2[0.2-9.2] P=0.831 |
||
|
Anaphylaxsis |
2/1,9 8.9[2.1-38] p=0.003 |
3/0.2 1.3[0.4-4.6] p=0.644 |
3/0.1 0.1[0.0-0.3] p<0.0001 |
5/5.3 28[9.7-76] p<0.0001 |
5/2.0 10[3.5-28] P<0.0001 |
|
|
Pregnancy |
4/0.3 4.5[1.3-16] p=0.020 |
6/0.1 0.5[0.2-1.9] P=0.348 |
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|
Hypertension |
4/0.3 5.4[1.4-20] p=0.012 |
5/0.1 0.5[0.1-1.7] P=0.24 |
1/1.1 12[1.4-98] P=0.022 |
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|
Malignancy |
6/0.1 2.2[0.3-18] P=0.47 |
*Data outlined as n(rate/100 years), RR=Risk ratio[95% CI], p-value
Conclusion:
These data provide support for the long-term and comparative safety of biologics in JIA pts. Overall, tolerance is acceptable. Surveillance of pharmacotherapy as provided by BIKER is an import approach especially in the case of long-term treatment of children. Differences between several biologics were noted and should be considered in daily patient care.
BiKeR is sponsored by unrestricted grants from Abbvie, Chugai, MSD, Novartis, Pfizer, Roche
To cite this abstract in AMA style:
Horneff G, Ganser G, Foeldvari I, Weller-Heinemann F, Minden K, Klein A. Pharmacovigilance of Biologics for Non-Systemic Juvenile Idiopathic Arthritis By the German Biologics Registry [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/pharmacovigilance-of-biologics-for-non-systemic-juvenile-idiopathic-arthritis-by-the-german-biologics-registry/. Accessed .ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacovigilance-of-biologics-for-non-systemic-juvenile-idiopathic-arthritis-by-the-german-biologics-registry/