Background/Purpose: Adipokines are cytokines/hormones primarily synthesized in white
adipose tissue. In rheumatoid arthritis (RA), some adipokines
have been associated with worse outcomes (1-3). The aim of this study was to
determine whether adipokine or insulin-like growth
factor 1 (IGF-1) serum measurement at baseline (BL) could predict future
disease activity and radiographic outcomes in patients with early RA.

Methods: Serum levels of adiponectin, leptin, IGF-1, and resistin
at RA diagnosis were analyzed in 330 patients enrolled in the Swedish
pharmacotherapy (SWEFOT) trial (207 with Body Mass Index (BMI)). All patients received
methotrexate (MTX) for 3 months. Thereafter, responders (DAS28≤3.2)
remained on MTX, while non-responders were randomized to triple therapy (MTX+sulfasalazine+hydroxychloroquine) or anti-TNF add-on (MTX+infliximab). The biomarker levels were divided into tertiles for further analyses, after adjustment for known
level differences to due sex (adiponectin and leptin) and age (IGF-1 SD score).
Disease activity (DAS28) and radiographic damage (Sharp-van der Heijde Score, SHS) were evaluated over 24 months.

Results: Adiponectin and leptin levels – but not IGF-1 or resistin
– were inversely and directly proportional, respectively, to BMI, which was
associated with worse DAS28 over 24 months. Disease activity did not differ
between tertile groups of leptin at BL (diagnosis),
but patients with high BL leptin had significantly higher DAS28 at 24 months
(Figure A). On the other hand, among initial MTX responders, high/moderate
(n=54) vs. low BL leptin (n=27) was associated with less rapid radiographic
progression from BL-12 months (DSHS≥5, 7.4% vs. 29.6%, p=0.036).
Disease activity did not differ significantly between adiponectin groups, however, they were directly proportional to BL SHS
with a numerical trend over time (Figure B).

Patients with low BL IGF-1 had higher DAS28 up until 3
months, but it was not significant thereafter (Figure C). In addition, more
radiographic progressors were observed between those
with low vs. high IGF-1 among initial MTX responders (BL-12 months, n=19 vs.
31, respectively: DSHS≥1, 68.4% vs. 32.3%, p=0.013; BL-24 months,
n=21 vs. 32: 81.0% vs. 50.0%, p=0.023). For resistin,
there were more progressors among those with high BL
levels among triple therapy-treated patients (Figure D), which was not observed
among the anti-TNF or MTX responder groups.

Conclusion: Differences in certain adipokines
and IGF-1 were associated with clinical and radiographic outcomes within
specific treatment groups. Thus, they may be useful predictors and may give insight
into pathogenic mechanisms influencing RA outcomes such as high BMI and disease
activity.

References:

1.  Meyer M, et al. Arthritis Res Ther. 2013;15(6):R210.

2.  Kontny E, et al. Scand J Rheumatol. 2015 May 14:1-6.

3.  Xibillé-Friedmann DX, et al. Clin Exp Rheumatol. 2015 May 1.