Table 1 Characteristics of registries used for identifying patients with RA in the post-marketing epidemiology abatacept study
|
ATTRA
|
DANBIO
[37, 38]
|
ROB-FIN
|
ORA
|
GISEA
|
BIOBADASER
|
SCQM
|
Country
|
Czech Republic
|
Denmark
|
Finland
|
France
|
Italy
|
Spain
|
Switzerland
|
Year of registry initiation
|
2002
|
2000
|
1999
|
2007
|
2008
|
2007
|
1996
|
Register design
|
National register
|
National register
|
National register
|
Multicenter registrya
|
Multicentre registry of bDMARDs
|
National register
|
National register
|
Age (years)
|
≥18
|
≥18
|
≥18
|
≥18
|
≥18
|
≥18
|
≥16
|
Data availability
|
8 Aug 2007 to 27 Nov 2017
|
15 June 2007 to 3 Dec 2017b
|
Sept 2007 to 31 Dec 2015
|
June 2007 to 3 June 2018
|
Through March 2014 (outcomes data) and through Nov 2015 (baseline data)
|
2007 to 15 Nov 2017c
|
Follow-up 1 Jan 2009 to 30 June 2017 (infections requiring hospitalization) or 1 Oct 2007 to 30 June 2017 (tuberculosis, malignancies)
|
Infection outcomes
Hospitalized infections
Opportunistic infections
Tuberculosis
|
Yes
Yes
Yes
|
Yes
Yes
Yes
|
Yes
NR
Yes
|
Yes
NR
NR
|
Yesd
NR
NR
|
Yes
Yes
Yes
|
Yes
NR
Yes
|
Malignancy outcomes
Overall malignancy
Breast cancer
Lung cancer
Lymphoma
|
Yes
Yes
Yes
Yes
|
Yes
Yes
Yes
Yes
|
Yes
Yes
Yes
Yes
|
Yes
Yese
Yese
Yese
|
Yesd
NR
NR
NR
|
Yes
Yes
Yes
Yes
|
Yes
Yes
Yes
Yes
|
Confirmation of infectionsf
|
MedDRA
|
ICD-10 codes
|
ICD-10 codes
|
Patient adverse event summary narratives
|
ICD codes
|
MedDRA
|
Identified by the treating rheumatologist
|
Confirmation of malignancy
|
MedDRA
|
ICD-10 codes
|
Linkage to national hospitalization discharge register (HILMO); ICD codesg
|
Patient adverse event summary narratives
|
ICD-codes based on the reports of pathologists
|
MedDRA
|
Identified by the treating rheumatologiste
|
aEstablished by the French Society of Rheumatology to investigate the long-term safety and effectiveness of intravenous abatacept in patients with RA.
bFor DANBIO, the study period corresponds to the time period when abatacept became available in Denmark; patients were also required to have follow-up data from the Danish National Patient Registry for the final report.
cBIOBADASER 2.0 and 3.0.
dReported as adverse event counts.
eReported in patient adverse event summary narratives.
fFor infections resulting in hospitalization, the infection code was the first code indicating the primary reason for hospitalization. In DANBIO, both primary and secondary codes were included as patients with RA may have had RA as the primary code.
gIf the description of the malignancy or the infection was not clear, an SCQM data analyst or study nurse could request additional information on the specific type or location of the malignancy.
ATTRA, Anti-TNF Therapy in Rheumatoid Arthritis; bDMARD, biologic disease-modifying antirheumatic drug; BIOBADASER, Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases; DANBIO, Danish Rheumatologic Database; GISEA, Italian Group for the Study of Early Arthritis; HILMO, Finnish nationwide social and healthcare data collection and reporting system; ICD, International Classification of Diseases; MedDRA, Medical Dictionary for Drug Regulatory Activities; NR, not reported; ORA, Orencia and Rheumatoid Arthritis; RA, rheumatoid arthritis; ROB-FIN, National Registry of Biological Treatment in Finland; SCQM, Swiss Clinical Quality Management.
Table 2 Baseline demographics and clinical characteristics of patients with RA in the post-marketing epidemiology abatacept study
|
ATTRA
|
DANBIO
|
ROB-FIN
|
ORA
|
GISEA
|
BIOBADASER
|
SCQMa
|
Number of patients
|
335
|
1213
|
362
|
976
|
433 with 770b total reported events
|
350
|
959 infection cohort
1053 malignancy cohort
|
Patient-years of exposure
|
862
|
4513
|
530
|
6119
|
NR
|
NR
|
1902 infection cohort
3683 malignancy cohort
|
Age (years), mean (SD)
|
52.1 (11.4)
|
57.2 (12.7)
|
54.7 (13.5)
|
58.0 (14.0)
|
First-line: 58.1 (NR)
Second-line: 58.5 (NR)
Other lines: 57.5 (NR)
|
57.5 (13.5)
|
58 (13)
|
Female, n (%)
|
270 (81)
|
941 (78)
|
308 (85)
|
771 (79)
|
654 (85)
|
276 (79)
|
~79%
|
Duration of RA (years), mean (SD)
|
8.1 (7.4)
|
10.1 (9.9)
|
12.8 (11.0)
|
14.0 (10.0)
|
First-line: 9.2 (NR)
Second-line: 11.3 (NR)
Other lines: 13.3 (NR)
|
NR
|
~11 (NR)
|
aPatient populations differed for the different outcomes; baseline characteristics of the patient populations for each outcome were similar.
bTotal for first-line, second-line, and other lines of treatment from 2007 to November 2015.
ATTRA, Anti-TNF Therapy in Rheumatoid Arthritis; BIOBADASER, Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases; DANBIO, Danish Rheumatologic Database; GISEA, Italian Group for the Study of Early Arthritis; NR, not reported; ORA, Orencia and Rheumatoid Arthritis; RA, rheumatoid arthritis; ROB-FIN, National Registry of Biological Treatment in Finland; SCQM, Swiss Clinical Quality Management; SD, standard deviation.
Table 3 Incidence rates/1000 patient-years (95% CI), number of events and patient-years of exposure for infections
|
ATTRA (n=335)
|
DANBIO (n=1213)
|
ROB-FIN
(n=362)
|
ORAa
(n=976)
|
GISEA
(n=433)
|
BIOBADASER
(n=350)
|
SCQMb
(n=959/974)
|
Infections requiring hospitalization
|
|
|
|
|
|
|
|
IR per 1000 p-y (95% CI)
|
6 (0, 12)
|
100 (87, 115)
|
84 (62, 110)
|
38c (NR)
|
43d (NR)
|
15 (8, 29)
|
4 (2, 8)
|
Number of events (p-y)
|
5 (NR)
|
196 (1955)
|
49 (NR)
|
298 (NR)
|
NR (NR)
|
9 (578)
|
7 (1902)
|
Opportunistic infections
|
|
|
|
|
|
|
|
IR per 1000 p-y (95% CI)
|
0
|
1 (0, 3)
|
NR
|
NRd
|
NR
|
14 (7, 27)
|
NR
|
Number of events (p-y)
|
0 (0)
|
2 (2233)
|
NR (NR)
|
NR (NR)
|
NR (NR)
|
8 (578)
|
NR (NR)
|
Tuberculosis
|
|
|
|
|
|
|
|
IR per 1000 p-y (95% CI)
|
6 (0, 12)
|
1 (0, 3)
|
0 (0, 6)
|
NR
|
NR
|
0
|
1.5 (1, 5)
|
Number of events (p-y)
|
5 (NR)
|
2 (2230)
|
0 (0)
|
NR (NR)
|
NR (NR)
|
0 (0)
|
3 (1941)
|
aNo CIs were provided in the report submitted by the French Society of Rheumatology to health authorities.
bThe sample size for infections requiring hospitalization was 959; for tuberculosis the sample size was 974. IRs are by exposure group with mid-imputed dates of occurrence.
cIntravenous antibiotic therapy and/or hospitalization.
dCalculated IR from the final study report from GISEA.
dFor ORA, NR means not reported in the report submitted to the French Health Authorities by the French Society of Rheumatology.
ATTRA, Anti-TNF Therapy in Rheumatoid Arthritis; BIOBADASER, Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases; CI, confidence interval; DANBIO, Danish Rheumatologic Database; GISEA, Italian Group for the Study of Early Arthritis; IR, incidence rate; NR, not reported; ORA, Orencia and Rheumatoid Arthritis; p-y, patient-years; ROB-FIN, National Registry of Biological Treatment in Finland; SCQM, Swiss Clinical Quality Management.
Table 4 Incidence rates/1000 patient-years (95% CI), number of events and patient-years of exposure for malignancies
|
ATTRA (n=335)
|
DANBIO (n=1213)
|
ROB-FIN
(n=362)
|
ORA
(n=976)
|
GISEA
(n=433)
|
BIOBADASER
(n=350)
|
SCQMa
(n=1053)
|
Overall malignancy
|
|
|
|
|
|
|
|
IR per 1000 p-y (95% CI)
|
9 (3, 16)
|
19 (15, 24)
|
7 (3, 16)
|
13 (NR)
|
3b (NR)
|
14 (7, 27)
|
9 (6, 12)
|
Number of events (p-y)
|
8 (NR)
|
70 (3642)
|
6 (NR)
|
92 (NR)
|
NR (NR)
|
8 (578)
|
32 (3683)
|
Breast
|
|
|
|
|
|
|
|
IR per 1000 p-y (95% CI)
|
2 (0, 9)
|
2 (1, 4)
|
2 (0, 9)
|
NR (NR)
|
NR
|
1.7 (0, 12)
|
NR
|
Number of events (p-y)
|
2 (NR)
|
6 (2939)
|
2 (NR)
|
NR
|
NR (NR)
|
1 (578)
|
NR (NR)
|
Lung
|
|
|
|
|
|
|
|
IR per 1000 p-y (95% CI)
|
1 (0, 8)
|
2 (1, 4)
|
1.2 (0, 7)
|
NR (NR)
|
NR
|
2 (0, 12)
|
NR
|
Number of events (p-y)
|
1 (NR)
|
8 (3775)
|
1 (NR)
|
NR
|
NR
|
1 (578)
|
NR
|
Lymphoma
|
|
|
|
|
|
|
|
IR per 1000 p-y (95% CI)
|
1 (0, 8)
|
1 (0, 2)
|
0 (0, 5)
|
0.7 (NR)
|
NR
|
0
|
NR
|
Number of events (p-y)
|
1 (NR)
|
3 (3779)
|
0 (NR)
|
5 (NR)
|
NR (NR)
|
0 (578)
|
NR (NR)
|
aIR is by exposure group with mid-imputed dates of occurrence.
bCalculated IR using first- and second-line abatacept counts from November 2015.
ATTRA, Anti-TNF Therapy in Rheumatoid Arthritis; BIOBADASER, Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases; CI, confidence interval; DANBIO, Danish Rheumatologic Database; GISEA, Italian Group for the Study of Early Arthritis; IR, incidence rate; NR, not reported; ORA, Orencia and Rheumatoid Arthritis; p-y, patient-years; ROB-FIN, National Registry of Biological Treatment in Finland; SCQM, Swiss Clinical Quality Management.