Background/Purpose: Sleep problems
affect over 60% of RA patients, but little is known about the relationship
between sleep and inflammation in RA. Our primary objective was to identify
associations between changes in sleep and changes in disease activity among RA
subjects starting DMARDs. We also examined differences in these associations
among those starting non-biologic vs. biologic DMARDs.

Methods: Individuals
with active RA were recruited from 4 academic medical centers and assessed
before and 12-weeks after starting a new DMARD. Subjects had to be starting a
DMARD due to active disease, meet 2010 ACR criteria for RA, and be taking
≤ 10 mg of prednisone daily. Primary outcomes were changes in the PROMIS
computerized adaptive test scores for Sleep-Related Impairment and Sleep
Disturbance, reported as T-scores with a general population mean of 50 ± 10 and
higher scores indicating worse sleep. The primary predictor was change in the
Clinical Disease Activity Index (CDAI). The minimal clinically important improvement
in CDAI is 6 for those with moderate baseline disease activity and 12 for those
with high baseline disease activity (Curtis 2015). Multivariable linear
regression models, adjusted for age, race, gender, RA duration and baseline
sleep measures, were used to identify associations between changes in CDAI and
changes in sleep. These associations were also examined in subgroup analyses
stratified by those starting non-biologic vs. biologic DMARDs.

Results: Of the 58
RA subjects seen to date, 23 (39.7%) started non-biologic DMARDs, and 35
(60.3%) started biologic DMARDs. The mean baseline CDAI was 23.1 ± 14.0. After
12 weeks of DMARD treatment, the mean change in CDAI was -9.6 ± 13.5. Decreases
in CDAI were associated with decreases in sleep-related impairment (β =
0.25; P = 0.01) but not with changes in sleep disturbance (β = 0.18;
P = 0.11). In subgroup analyses, subjects who started non-biologic
DMARDs had greater, though not statistically significant, decreases in CDAI
(-12.9 ± 15.5), sleep disturbance (-3.8 ± 13.4) and sleep-related impairment (-4.5
± 9.8) than subjects who started biologic DMARDs (CDAI: -7.5 ± 11.8; sleep
disturbance: -3.1 ± 7.4; sleep-related impairment: -2.7 ± 10.2) despite similar
baseline values. Decreases in CDAI were significantly associated with decreases
in sleep disturbance and sleep-related impairment for those who started
biologic DMARDs. No associations were observed in those starting non-biologic
DMARDs (Table).

Conclusion: The magnitude of
association between change in CDAI and change in sleep disturbance and
sleep-related impairment differed among those who started non-biologic DMARDs
vs. biologic DMARDs. These differences may reflect different mechanisms
underlying improvements in sleep. A large, randomized clinical trial, directly
comparing different types of DMARDs, is needed to elucidate the link between
changes in inflammation and changes in sleep in RA.