Investigation of Vitamin D Supplement Use, Rheumatoid Arthritis-Related Autoimmunity and Joint Signs Among Those at Increased Risk for the Development of Rheumatoid Arthritis

Elizabeth A. Bemis¹, Ryan W. Gan², Marie L. Feser³, Michael H. Weisman⁴, James R. O'Dell⁵, Ted R. Mikuls⁵, Jane H. Buckner⁶, Peter K. Gregersen⁷, Richard M. Keating⁸, M. Kristen Demoruelle⁹, Kevin D. Deane¹⁰, V. Michael Holers¹¹ and Jill M. Norris¹², ¹Epidemiology, Epidemiology, Colorado School of Public Health, Aurora, CO, ²Colorado School of Public Health, University of Colorado Denver, Aurora, CO, ³Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, ⁴Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, ⁵University of Nebraska Medical Center, Omaha, NE, ⁶Benaroya Research Institute at Virginia Mason, Seattle, WA, ⁷Feinstein Insititute for Medical Research, Manhasset, NY, ⁸Division of Rheumatology, Scripps Health, La Jolla, CA, ⁹Rheumatology, University of Colorado School of Medicine, Aurora, CO, ¹⁰Division of Rheumatology, U Colo Denver, Aurora, CO, ¹¹Rheumatology Division, Univ of Colorado School of Med, Aurora, CO, ¹²University of Colorado Denver, Aurora, CO

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: autoantibodies and rheumatoid arthritis (RA), Vitamin D

Session Information

Date: Monday, November 9, 2015

Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:
Vitamin D has immunomodulatory
properties, and could be a protective factor against rheumatoid arthritis (RA).
Anti-cyclic citrullinated peptide (anti-CCP)
autoantibodies and swollen small joints of the hand (wrist and metacarpophalangeal [MCP] joints) are characteristics of RA
that can be present years prior to the development of classifiable RA by
established criteria. We investigated the associations between anti-CCP2
positivity and swollen joint symptoms with self-reported vitamin D supplement
use in a population without RA, but at risk for development of RA.

Methods: The
multicenter Studies of the Etiology of RA (SERA) cohort study recruited
subjects who are classified as RA-free at visit, but at increased genetic
and/or family risk for RA. At baseline, we assessed the association between
self-reported vitamin D supplement use over the past year and presence of the
two preclinical outcomes, anti-CCP2 positivity and having >= 1 swollen wrist and/or MCP joint. Three vitamin D exposure
variables were created including a yes or no response, source of vitamin D
(none, multivitamin or single supplement), and total months of use (0 months,
1-12 months or >12 months [i.e. those taking more than one vitamin D supplement]).
These self-reported variables were found to be associated with 25-hydroxyvitamin D (25OHD) plasma concentrations that were available in a subset of the study population. Logistic
regression models were used to estimate the independent association between the
three exposure variables and the two outcomes, adjusting for age, sex, race,
shared epitope, current smoking, cohort (first degree relative vs not), site of recruitment and use of other supplements.

Results: The analysis cohort (n=2,383 at-risk subjects) was 69% female, 80% non-Hispanic white, with a mean age
of 44.6 years. We identified 44 anti-CCP2 subjects and 57 subjects
with >= 1 swollen joint at baseline.
Vitamin D supplement use was not associated with anti-CCP2 positivity
(Table). A marginally significant association was seen with joint signs, where
those with >= 1 swollen joint were about half as likely to have been taking
vitamin D supplements in the previous year (Table).

Table: Odds ratios (OR) for anti-CCP2 positivity and >=1 swollen joint in relation to each vitamin D exposure variable.
	*Outcome*
	Anti-CCP2 n=44 positive subjects		>= 1 swollen joint* n=57 positive subjects
Any Vitamin D Supplement	OR (95% CI)	p-value	OR (95% CI)	p-value
No	1.00	Ref	1.00	Ref
Yes	1.92 (0.47-7.92)	0.37	0.47 (0.22-1.01)	0.07
Vitamin D Source
No vitamin D supplement	1.00	Ref	1.00	Ref
From a Multivitamin only	1.80 (0.43-7.55)	0.42	0.47 (0.22-1.04)	0.08
From a Single supplement containing vitamin D	2.37 (0.49-11.43)	0.28	0.47 (0.17-1.32)	0.19
Vitamin D Duration
0 Months (no vitamin D supplement)	1.00	Ref	1.00	Ref
1-12 Months	1.15 (0.26-5.05)	0.85	0.46 (0.22-1.05)	0.07
>12 Months	2.45 (0.46-13.08)	0.29	0.45 (0.14-1.38)	0.16
Adjusted for age, sex, race, cohort, recruitment site, current smoking status, Shared Epitope, and other supplement use. *The sample size for the joint outcome analysis is n=1955, which is reduced because our off-site visits did not include a joint examination.

Conclusion: Vitamin D supplement use was not associated with RA-related
autoimmunity in at-risk subjects. An inverse trend between joint signs and
vitamin D supplement use suggests the need for further research to examine the
role of vitamin D in the later stages of pre-clinical RA.

Disclosure: E. A. Bemis, None; R. W. Gan, None; M. L. Feser, None; M. H. Weisman, None; J. R. O'Dell, None; T. R. Mikuls, None; J. H. Buckner, None; P. K. Gregersen, Illumina Inc., 1,Janssen Pharmaceutica Product, L.P., 5,Biogen, Idec, 5; R. M. Keating, None; M. K. Demoruelle, None; K. D. Deane, None; V. M. Holers, Shared patent with Stanford University for use of biomarkers to predict clinical phenotypes in rheumatoid arthritis., 7; J. M. Norris, None.

To cite this abstract in AMA style:

Bemis EA, Gan RW, Feser ML, Weisman MH, O'Dell JR, Mikuls TR, Buckner JH, Gregersen PK, Keating RM, Demoruelle MK, Deane KD, Holers VM, Norris JM. Investigation of Vitamin D Supplement Use, Rheumatoid Arthritis-Related Autoimmunity and Joint Signs Among Those at Increased Risk for the Development of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/investigation-of-vitamin-d-supplement-use-rheumatoid-arthritis-related-autoimmunity-and-joint-signs-among-those-at-increased-risk-for-the-development-of-rheumatoid-arthritis/. Accessed .

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