Session Information
Date: Monday, October 22, 2018
Session Title: Pediatric Rheumatology – Clinical Poster II: Autoinflammatory Disorders, Scleroderma, and Miscellaneous
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Long-term surveillance of biologic drugs is particularly important in pediatric patients(pts). Since 2001, the German Biologics JIA Registry (BIKER) is allowing to follow up of an unlimited number of patients in routine clinical care. Safety with regard to adverse events of special interest was assessed.
Methods: The BIKER database was used to identify systemic JIA pts exposed to biologics. Safety assessments were based on adverse events (AE) reports for 25 predefined AEs of special interest (AESI). Events per 100 patient-years (PY) of exposure were calculated using AEs reported after first dose through 70 days after last dose. Rates were compared by Wald test. Only 5 pts receiving abatacept and 2 with infliximab were excluded from the Analysis.
Results: 278 pts received 388 biologics courses with a total exposure time of 765 PY. 152 pts received Etanercept (ETA,366 PY), 95 Tocilizumab (TOC,171 PY), 73 Anakinra (ANA,121 PY), 49 Canakinumab (CAN,69 PY) and 19 Adalimumab (ADA,38 PY). Differences in pts characteristics and concomitant treatment between these cohorts were noted. A total of 456 AE (rate 59.5/100 years), 94 SAE (12.3) and 95 AESI (12.4) were reported. The most common AESI were serious or medically important infections (30), cytopenias (21), macrophage activation syndrome (MAS,13), anaphylaxis (11), hepatic events (10), malignancies (4) and others occurring only once (other autoimmunopathies, chronic inflammatory bowel disease, depression, demyelinisation, thrombotic disorder, uveitis). There were marked differences in the rate of AESI between the cohorts with different biologics (table). Risk Ratios for serious and medically important infections were significantly higher with TOC and lower with ETA. Risk ratios for cytopenias were significantly higher with CAN and TOC. MAS occurred significantly more frequently with TOC and CAN and less frequently with ETA. Risk ratios for hepatic events were significantly higher in the TOC cohort and lower with ETA. Risk ratio for cyctopenias was significantly higher with TOC. Risk ratios for anaphylaxis were significantly higher with TOC probably due to the intravenous route of application. There was no death, no cardiovascular event, no bleeding, no intestinal perforation, pregnancy or opportunistic infection in this cohort
|
Biologic |
ADA |
ANA |
CAN |
ETA |
TOC |
|
Pat/exposure years |
19/37.6 |
73/120.9 |
49/69.0 |
152/366.2 |
95/171.7 |
|
AE n(rate/100PY) |
5(13.3) |
47(38.9) |
109(157) |
86(23.4) |
209(121) |
|
SAES n(rate/100PY) |
0 |
12(9.9) |
17(24.6) |
17(4.6) |
48 (27.9) |
|
AESI n(rate/100PY) |
0 |
12(9.9) |
18(26.1) |
14(3.8) |
52(30.2) |
|
Serious and medically important Infection |
0 |
8(6.62) 1.9(0.9-4.4) |
4(5.8) 1.6(0.5-4.4) |
4(1.09) 0.16(0.1-0.5) P<0.0001 |
14(8.15) 3.0(1.5-6.2) P=0.025 |
|
Cytopenia |
0 |
2(1.65) 1.8(0.4-7.7) |
6(8.7) 4.0(1.5-10) P=0.0039 |
1(0.27) 0.1(0-0.4) P=0.04 |
12(6.99) 4.7(1.9-11) P=0.0005 |
|
MAS |
0 |
1(0.83) 0.5(0.1-4.2) |
3(4.35) 3.8(1.0-14) 0.0495 |
3(0.82) 0.3(0.1-1.1) |
6(3.49) 4.2(1.3-14) P=0.019 |
|
Anaphylaxis |
0 |
0 |
1(1.45) 0.9(0.1-7.1) |
0 |
10(5.82) 17(3.7-79) P=0.0002 |
|
Hepatic Event |
0 |
0 |
1(1.45) 1.1(0.1-8.8) |
1(0.27) 0.1(0-1.0) P=0.045 |
8(4.66) 13.8(2.9-65) P=0.0009 |
|
Malignancy |
0 |
1(0.83) 1.8(0.2-17) |
0 |
2(0.55) 1.1(0.1-7.7) |
1(0.58) 1.2(0.1-11) |
|
Autoimmune disease |
0 |
1(1.45) 10(0.6-161) |
|||
|
IBD |
0 |
1(0.27 1.1(0.1-17) |
|||
|
Depression |
0 |
1 (1.45) 10(0.6-161) |
|||
|
Demyelination |
0 |
0 |
1(0.27 1.1(0.1-17) |
||
|
Thrombotic event |
0 |
0 |
0 |
0 |
1(0.58) 3.5(0.2-55) |
|
Uveitis |
0 |
1(0.27 1.1(0.1-17) |
*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. Interpretation of these data requires caution.
BiKeR is sponsored by unrestricted grants from Abbvie, Chugai, MSD, Novartis, Pfizer, Roche.
To cite this abstract in AMA style:
Horneff G, Ganser G, Hospach T, Foeldvari I, Borte M, Weller-Heinemann F, Minden K, Klein A. Pharmacovigilance of Biologics for Systemic Juvenile Idiopathic Arthritis Patients By the German Biologics Registry [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/pharmacovigilance-of-biologics-for-systemic-juvenile-idiopathic-arthritis-patients-by-the-german-biologics-registry/. Accessed April 9, 2020.« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacovigilance-of-biologics-for-systemic-juvenile-idiopathic-arthritis-patients-by-the-german-biologics-registry/