Session Information
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: INA populations have a high prevalence of seropositive RA, often with severe disease. The risk of RA in family members of RA patients, particularly first-degree relatives (FDR), is estimated to be up to 4 times that of the general population. We prospectively followed a cohort of unaffected family members of INA RA patients to determine the incidence of inflammatory arthritis (IA).
Methods: Family members of INA RA probands were recruited and followed longitudinally between 2005-2017. At baseline, participants were examined to confirm absence of synovitis and questionnaires regarding joint symptoms, lifestyle, and comorbidities were administered. Serum was tested for ACPA (anti-CCP3 ELISA) and IgM RF seropositivity. Seropositive individuals were re-evaluated annually and seronegative individuals every three years. Participants were instructed to contact the investigators if symptoms suggestive of IA occurred and were re-evaluated at that time. Diagnosis of IA required one or more swollen joints deemed to represent synovitis by a study rheumatologist. Individuals included in the analysis had a least two visits, 6 months or more apart. To calculate the incidence of IA, number of IA cases was used as the numerator, and total years of follow-up of the entire cohort served as the denominator.
Results: 374 family members (314 from Manitoba, 60 from Alaska) were enrolled. The majority (75%) were FDR. Total follow-up time for the cohort was 1,940 person-years. 18 (4.8%) people developed IA after a mean of 4.8 (IQR 3.6-6.1) years, and 15/18 (83%) met the 2010 ACR/EULAR criteria for RA. Baseline cohort characteristics are in Table 1. The rate of IA development was 9.2 cases per 1000 person years of follow-up (0.9% annually). 6/18 of the IA group was ACPA and RF seronegative at baseline with a median time to transition of 5.6 (±1.1) years, whereas the 5/18 who were ACPA/RF positive at baseline developed IA after 3.2 (±2.2) years (Table 2). Interestingly, 7/12 relatives who were ACPA/RF positive at baseline had not developed IA after being followed for a mean of 5.1 years (± 2.2), and many individuals who were seropositive at any given time subsequently became seronegative.
Conclusion: This prospective longitudinal cohort study of the relatives of INA RA patients is the first to establish the incidence of IA in this high-risk population. As expected, ACPA+/RF+ seropositivity is associated with the highest rates of IA development and shortest latency period. Importantly, the lack of IA development in the majority of seropositive individuals, including ACPA+/RF+, suggests the transition to clinically detectable disease relates to other unknown factors.
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Table 1. Baseline characteristics of individuals with longitudinal follow-up. |
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Transitioner, n=18 |
Non-Transitioner, n=356 |
p-value |
|
|
Female |
14 (77.8) |
234 (65.7) |
0.29 |
|
Age (years), mean (SD) |
30.0(11.5) |
37.1 (12.8) |
0.02 |
|
Duration of follow-up (years), mean (SD) |
4.8 (2.4) |
5.2 (2.7) |
0.57 |
|
History of smoking |
16 (88.9) |
272 (76.5) |
0.24 |
|
Pack years smoking, med (IQR) |
3.5 (1.2-12.0) |
5 (0.8-12.6) |
0.41 |
|
BMI (kg/m2), mean (SD) |
28.9 (7.9) |
32.4 (7.1) |
0.06 |
|
Diabetes |
0 (0) |
58 (19.5) |
0.13 |
|
Any HLA shared epitope (SE) |
8/15 (53.3) |
114/192(59.4) |
0.65 |
|
HLA 1402 positive |
9/15 (60.0) |
93/234(39.7) |
0.07 |
|
HLA SE double positive |
5/15 (33.3) |
30/192(15.6) |
0.10 |
|
CRP (mg/L), med (IQR) |
2.4 (1.1-5.7) |
3.4 (1.7-7.0) |
0.44 |
|
ACPA negative † |
8 (44.4) |
321 (91.2) |
0.01 |
|
ACPA positive† |
10 (55.5) |
31 (8.8) |
0.01 |
|
ACPA strong positive† |
7 (38.9) |
11 (3.1) |
0.01 |
|
RF negative‡ |
11(61.1) |
295 (84.7) |
0.02 |
|
RF positive‡ |
7 (38.9) |
53 (15.2) |
0.01 |
|
RF strong positive‡ |
4 (22.2) |
11 (3.2) |
0.01 |
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RF and ACPA positive‡ |
5 (27.8) |
7 (2.0) |
0.01 |
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Symptoms |
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Hand pain |
10/16 (62.5) |
143/279 (51.3) |
0.381 |
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Other joint pain |
10/15 (66.7) |
155/280 (55.4) |
0.390 |
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Hand swelling |
6/16 (37.5) |
99/282 (35.1) |
0.845 |
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Other joint swelling |
7/16 (43.8) |
79/279 (28.3) |
0.405 |
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Hand stiffness |
8/17(47.1) |
109/281 (38.3) |
0.498 |
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Other joint stiffness |
8/16 (50) |
114/280 (40.7) |
0.407 |
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Values are reported as n (%), unless otherwise noted. * Strong positive values generated according to ACR definition. Strong positive ³3x’s upper limit of normal based on manufacturers cut-off. † n=352 in non-transitioner subset ‡ n=348 in non-transitioner subset |
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Table 2. Baseline autoantibody groups and development of inflammatory arthritis. |
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ACPA-/RF- n=285 |
ACPA-/RF+ n=48 |
ACPA+/RF- n=29 |
ACPA+/RF+ n=12 |
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Time at risk, person-years |
1472.1 |
276.2 |
137.3 |
51.5 |
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Cases of IA (% in autoantibody group) |
6 (2.1) |
2 (4.2) |
5 (17.2) |
5 (41.7) |
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Cases of IA/ 1000 person years |
4.1 |
7.2 |
36.4 |
97.1 |
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Time to IA, years |
5.6 (1.1) |
5.5 (5.0) |
4.7 (2.7) |
3.2 (2.2) |
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Time to ACPA positivity, years |
2.3 (1.7) |
2.2 (n=1) |
– |
– |
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Number cases meeting ACR RA criteria |
5/6 |
1/2 |
5/5 |
4/5 |
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Values are reported as mean with standard deviation unless stated. Seropositivity of ACPA and RF based on manufacturers cut-off level. |
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To cite this abstract in AMA style:
Tanner S, Smolik I, Dufault B, Hitchon C, Robinson D, Ferucci E, El-Gabalawy H. Risk of Inflammatory Arthritis Development in the Family Members of Indigenous North American (INA) RA Patients [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/risk-of-inflammatory-arthritis-development-in-the-family-members-of-indigenous-north-american-ina-ra-patients/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-inflammatory-arthritis-development-in-the-family-members-of-indigenous-north-american-ina-ra-patients/