Improved Outcomes in RA With Obesity After Weight Loss

In This Article

Abstract and Introduction

Abstract

Objective: To examine whether a weight loss intervention programme improves RA disease activity and/or musculoskeletal ultrasound synovitis measures in obese RA patients.

Methods: We conducted a proof-of-concept, 12-week, single-blind, randomized controlled trial of obese RA patients (BMI ≥ 30) with 28-joint DAS (DAS28) ≥ 3.2 and with evidence of power Doppler synovitis. Forty patients were randomized to the diet intervention (n = 20) or control group (n = 20). Diet intervention consisted of a hypocaloric diet of 1000–1500 kcal/day and high protein meal replacements. Co-primary outcomes included change in DAS28 and power Doppler ultrasound (PDUS)-34. Clinical disease activity, imaging, biomarkers, adipokines and patient-reported outcomes were monitored throughout the trial. Recruitment terminated early. All analyses were based on intent-to-treat for a significance level of 0.05.

Results: The diet intervention group lost an average 9.5 kg/patient, while the control group lost 0.5 kg (P < 0.001). Routine Assessment of Patient Index Data 3 (RAPID3) improved, serum leptin decreased and serum adiponectin increased significantly within the diet group and between the groups (all P < 0.03). DAS28 decreased, 5.2 to 4.2, within the diet group (P < 0.001; −0.51 [95% CI −1.01, 0.00], P = 0.056, between groups). HAQ-Disability Index (HAQ-DI) improved significantly within the diet group (P < 0.04; P = 0.065 between group). Ultrasound measures and the multi-biomarker disease activity score did not differ between groups (PDUS-34 −2.0 [95% CI −7.00, 3.1], P = 0.46 between groups).

Conclusion: Obese RA patients on the diet intervention achieved weight loss. There were significant between group improvements for RAPID3, adiponectin and leptin levels, and positive trends for DAS28 and HAQ-DI. Longer-term, larger weight loss studies are needed to validate these findings, and will allow for further investigative work to improve the clinical management of obese RA patients.

Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02881307

Introduction

RA patients with obesity represent >30% of North American RA patients^[1,2] and are less likely to attain remission^[3–5] and optimal response to therapy than non-obese patients.^[4–6] They also have evidence of more joint deformity, functional disability, decreased quality of life and increased cardiovascular risks than non-obese patients.^[3,7,8]

Although clinicians advocate for weight loss because of substantive economic and public health concerns,^[8–10] there is still a lack of definitive evidence about the effects of weight loss on RA disease activity. In this context, there are no standardized interventions for the reduction of obesity rates in RA patients. Exercise is considered safe^[11] but a broad implementation of exercise regimens in RA patients is limited by fears of causing injury and/or aggravating disease, in addition to being highly variable in terms of weight loss results.^[12–14] Data suggest that hypocaloric diets have been successful in producing weight loss and health benefits, and the World Health Organization recommends a minimum of 5% body weight loss in obese patients.^[7,15,16] Yet, few studies have investigated the impact of weight loss in obese RA patients through dietary modifications,^[17,18] and no studies have examined its impact comprehensively on RA disease outcomes (clinical, imaging and biomarker measures).

Here we report the results of a proof-of-concept, 12-week, randomized controlled trial (RCT) of a hypocaloric diet in RA patients with obesity to evaluate the effects of weight loss on clinical, imaging and biomarker/adipokine outcomes.

Table 1. Baseline characteristics
Characteristic	All participants (n = 40)	Diet intervention (n = 20)	Control (n = 20)
Age, mean (S.D.), years	55.0 (13.2)	57.7 (11.9)	52.2 (14.2)
Female, n (%)	36 (90.0)	19 (95.0)	17 (85.0)
Caucasian, n (%)	30 (75.0)	16 (80.0)	14 (70.0)
Seropositive, n (%)	32 (80.0)	16 (80.0)	16 (80.0)
RA disease duration, mean (S.D.), years	12.8 (11.8)	11.6 (10.3)	14.0 (13.3)
BMI, mean (S.D.), kg/m²	34.8 (5.7)	33.4 (5.7)	36.2 (5.4)
Baseline prednisone use, n (%)	7 (17.5)	2 (10.0)	5 (25.0)
Baseline prednisone dose, mean (S.D.), mg	2.6 (1.8)	3.8 (1.8)	2.1 (1.7)
csDMARD, n (%)	20 (50.0)	10 (50.0)	10 (50.0)
bDMARD/tsDMARD, n (%)	22 (55.0)	9 (45.0)	13 (65.0)
DAS28/ESR, mean (S.D.)	5.0 (1.1)	5.2 (1.2)	4.7 (1.0)
CDAI, mean (S.D.)	24.6 (10.1)	25.5 (9.7)	23.7 (10.6)
PDUS-34, mean (S.D.)	18.7 (11.3)	20.8 (10.8)	16.7 (11.8)
GSUS-34, mean (S.D.)	30.7 (11.8)	31.7 (12.4)	29.7 (11.3)
MBDA, mean (S.D.)	40.1 (12.6)	42.4 (14.5)	37.7 (10.2)
HAQ-DI, mean (S.D.)	0.90 (0.59)	0.8 (0.5)	1.0 (0.7)
RAPID3, mean (S.D.)	11.3 (4.7)	12.0 (5.0)	10.7 (4.5)
Patient global, mean (S.D.)	4.5 (2.0)	5.0 (2.1)	4.0 (1.7)
Patient pain, mean (S.D.)	4.6 (2.3)	5.3 (2.4)	3.8 (2.0)

bDMARD: biologic DMARD; CDAI: Clinical Disease Activity Index; csDMARD: conventional synthetic DMARD; DAS28/ESR: 28-joint DAS using ESR; GSUS: grey scale synovial hypertrophy; HAQ-DI: HAQ-Disability Index; MBDA: multi-biomarker disease activity; PDUS: power Doppler ultrasound; RAPID3: Routine Assessment of Patient Index Data 3; tsDMARD: targeted synthetic DMARD.

Table 2. Metrics of weight loss
	Diet intervention	Control	Between group P-value
Weight, mean (S.D.), kg			<0.001
Baseline	89.6 (15.7)	96.8 (16.4)
12 weeks	80.1 (5.5)	96.3 (16.7)
Change	−5.6 (3.5)	−0.3 (2.7)
Within group P-value	<0.001	0.684
BMI, mean (S.D.), kg/m²			<0.001
Baseline	33.4 (5.7)	36.2 (5.4)
12 weeks	29.9 (2.0)	36.3 (5.5)
Change	−2.0 (1.1)	−0.1 (1.1)
Within group P-value	<0.001	0.740
% body fat, mean (S.D.)			<0.001
Baseline	47.4 (4.8)	47.1 (5.9)
12 weeks	44.0 (4.7)	47.2 (5.6)
Change	−2.4 (1.9)	0.1 (1.7)
Within group P-value	<0.001	0.758
%Weight loss at 12 weeks, n (%)
>5%	13 (72.2)	2 (10.5)	<0.001
>10%	2 (11.1)	0	0.230

Table 3. Disease activity measures and patient reported measures
	Diet intervention	Control	Between group P-value
ACR20 at 12 weeks, n (%)	5 (27.8%)	1 (5.3%)	0.090
CDAI, mean (SD)			0.292
Baseline	25.5 (9.7)	23.7 (10.6)
12 weeks	16.5 (7.5)	18.9 (10.0)
Change	−7.2 (3.9)	−4.4 (10.8)
Within group P-value	<0.001	0.025
FACIT, mean (S.D.)			0.759
Baseline	36.8 (9.0)	37.1 (10.7)
12 weeks	40.7 (9.0)	38.1 (10.2)
Change	4.0 (7.1)	1.0 (7.1)
Within group P-value	0.447	0.753
GSUS-34, mean (S.D.)			0.792
Baseline	31.7 (12.4)	29.7 (11.3)
12 weeks	24.1 (9.3)	23.1 (12.3)
Change	−6.5 (6.9)	−5.8 (9.9)
Within group P-value	0.004	0.013
28 TJC, mean (S.D.)
Baseline	10.1 (5.3)	7.9 (6.5)	0.099
12 weeks	5.3 (4.3)	6.1 (4.7)
Change	−4.2 (3.3)	−1.3 (6.6)
Within group P-value	0.002	0.130
28 SJC, mean (S.D.)			0.831
Baseline	6.2 (3.3)	6.7 (4.6)
12 weeks	4.7 (2.4)	5.6 (4.0)
Change	−0.9 (2.4)	−1.2 (4.9)
Within group P-value	0.329	0.194
ESR			0.317
Baseline	29.0 (26.5)	24.0 (18.0)
12 weeks	19.9 (14.9)	24.6 (19.0)
Change	−3.1 (11.5)	0.7 (9.8)
Within group P-value	0.261	0.779

CDAI: Clinical Disease Activity Index; FACIT: Functional Assessment of Chronic Illness Therapy; GSUS: Grey Scale Synovial Hypertrophy; SJC: swollen joint count; TJC: tender joint count.

Table 4. Biomarkers and adipokine measures
	Diet intervention	Control	Between group P-value
MBDA score, median (Q1, Q3)			0.303
Baseline	37.5 (34, 52.5)	39 (36, 46)
12 weeks	38 (28, 46)	39 (27, 50)
Within group P-value	0.361	0.587
Adiponectin^a, median (Q1, Q3)			0.037
Baseline	10 (8, 17)	9.5 (4.7, 12)
12 weeks	11 (5, 18)	9 (6, 23)
Within group P-value	0.198	0.087
Leptin, median (Q1, Q3)			0.024
Baseline	39.2 (21.9, 60)	42.2 (26.8, 105.7)
12 weeks	24.6 (17.4, 32.1)	57.2 (23.7, 110.9)
Within group P-value	0.009	0.612
Visfatin^a, median (Q1, Q3)			0.473
Baseline	0.65 (0.6, 0.9)	0.65 (0.6, 0.9)
12 weeks	0.9 (0.6, 1.2)	0.95 (0.6, 1.2)
Within group P-value	0.452	0.797

^aAdiponectin and visfatin values were analysed on the log scale to account for strong right-skewness. MBDA: multi-biomarker disease activity.

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Improved Outcomes in Rheumatoid Arthritis With Obesity After a Weight Loss Intervention

Randomized Trial

Abstract and Introduction

Abstract

Introduction

Improved Outcomes in Rheumatoid Arthritis With Obesity After a Weight Loss Intervention

Randomized Trial

Abstract and Introduction

Abstract

Introduction

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