Longitudinal Assessment of Body Composition and Inflammatory Status in Rheumatoid Arthritis During TNF Inhibitor Treatment: A Pilot Study
Abstract
1. Introduction
2. Results
2.1. Baseline Characteristics of the Sample
2.2. Study of Body Composition, Adipokines, and Inflammatory Factors at Baseline and at 6 Months in Patients with RA Treated with TNF Inhibitors
2.3. Clinical and Laboratory Characteristics of RA Associated with Lean Mass
2.4. Multivariate Analysis
3. Discussion
4. Materials and Methods
4.1. Study Design, Data Source, and Sampling
4.1.1. Patients
4.1.2. Controls
4.2. Study Protocol
4.2.1. Baseline Evaluation of Participants
4.2.2. Prospective Evaluation of Patients with RA
4.3. Definition of Variables
4.3.1. Anthropometric Variables and Body Composition
4.3.2. Cytokines and Inflammatory Activity
4.3.3. Remaining Variables
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
RA | rheumatoid arthritis |
RF | rheumatoid factor |
ACPA | anti-citrullinated peptide antibody |
DAS28 | 28-joint Disease Activity Score |
CRP | C-reactive protein |
HAQ | health Assessment Questionnaire |
IL | interleukin |
DMARD | disease-modifying antirheumatic drug |
BMI | body mass index |
DXA | dual-energy X-ray absorptiometry |
FMI | fat mass index |
FFMI | fat-free mass index |
LMI | lean mass index |
RSMI | relative skeletal mass index |
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Variable | RA n = 70 | Controls n = 70 | p-Value |
---|---|---|---|
Epidemiological | |||
Female sex, n (%) | 57 (81.4) | 57 (81.4) | 1.000 |
Age, years, mean (SD) | 56.2 (12.3) | 54.6 (17.6) | 0.528 |
White race, n (%) | 70 (100) | 71 (100) | 1.000 |
Comorbid conditions | |||
Any, n (%) | 70 (100.0) | 45 (64.3) | <0.001 |
No. of comorbid conditions, median (IQR) | 2.0 (1.0–3.0) | 1.0 (0.0–2.0) | 0.021 |
Multimorbidity, n (%) | 38 (54.3) | 26 (37.1) | 0.042 |
Charlson Comorbidity Index, median (IQR) | 1.0 (1.0–2.0) | 0.0 (0.0–0.0) | <0.001 |
Age-adjusted Charlson Comorbidity Index, median (IQR) | 2.0 (1.7–3.0) | 1.0 (0.7–2.0) | <0.001 |
Dyslipidemia, n (%) | 16 (22.9) | 13 (18.6) | 0.532 |
Arterial hypertension, n (%) | 20 (28.6) | 18 (25.7) | 0.704 |
Smoking | 0.037 | ||
Nonsmoker, n (%) | 31 (44.3) | 46 (65.7) | |
Exsmoker, n (%) | 21 (30.0) | 12 (17.1) | |
Smoker, n (%) | 18 (25.7) | 12 (17.1) | |
Obesity, n (%) | 20 (28.6) | 14 (20.0) | 0.237 |
Diabetes mellitus, n (%) | 8 (11.4) | 5 (7.1) | 0.382 |
Osteoporosis, n (%) | 12 (17.1) | 9 (12.9) | 0.478 |
Variables associated with RA | |||
Disease duration, median (IQR), months | 76.0 (34.6–184.8) | - | - |
Diagnostic delay, median (IQR), months | 7.0 (3.9–11.52) | - | - |
Erosions, n (%) | 35 (50.0) | - | - |
RF positive (>10 U/mL), n (%) | 60 (85.7) | 0 (0.0) | <0.001 |
ACPA positive (>20 U/mL), n (%) | 56 (80.0) | 0 (0.0) | <0.001 |
ACPA high > 340 U/mL, n (%) | 21 (30.0) | 0 (0.0) | <0.001 |
DAS28-CRP, mean (SD) | 4.9 (1.15) | - | - |
DAS28-CRP, cumulative, mean (SD) | 3.7 (0.9) | - | - |
HAQ, mean (SD) | 1.4 (0.7) | - | - |
HAQ, cumulative, mean (SD) | 1.0 (0.5) | - | - |
Treatment | |||
csDMARDs, n (%) | 70 (100.0) | - | - |
Methotrexate, n (%) | 45 (64.3) | - | - |
Hydroxychloroquine, n (%) | 11 (15.7) | - | - |
Leflunomide, n (%) | 11 (15.7) | - | - |
Sulfasalazine, n (%) | 19 (27.1) | - | - |
Corticosteroids, mg/d, mean (SD) | 5.0 (0.0–7.5) | 0.0 (0.0–0.0) | |
Corticosteroids, n (%) | 52 (74.3) | 0 (0.0) |
Variable | RA n = 70 | Controls n = 70 | p-Value |
---|---|---|---|
Anthropometric characteristics | |||
BMI, kg/m2, mean (SD) | 27.8 (4.7) | 26.9 (4.6) | 0.545 |
Classification of BMI (WHO) | 0.122 | ||
Low weight (BMI < 18.5), n (%) | 0 (0.0) | 0 (0.0) | |
Normal weight (BMI 18.5–24.9), n (%) | 19 (27.1) | 27 (38.6) | |
Overweight (BMI 25.0–29.9), n (%) | 32 (45.7) | 33 (47.1) | |
Obesity, Grade I (BMI 30.0–34.5), n (%) | 15 (21.4) | 8 (11.4) | |
Obesity, Grade II (BMI 35.0–39.9), n (%) | 4 (5.7) | 1 (1.4) | |
Obesity, Grade III (BMI ≥ 40), n (%) | 0 (0.0) | 1 (1.4) | |
Waist circumference, cm, median (IQR) | 96.5 (86.5–105.7) | 89.5 (86.0–100.0) | 0.080 |
Hip circumference, cm, mean (SD) | 107.1 (9.4) | 103.5 (8.7) | 0.096 |
Waist–hip index, mean (SD) | 0.9 (0.1) | 0.8 (0.1) | 0.383 |
Body composition by DXA | |||
Total fat mass, kg, mean (SD) | 29.1 (9.4) | 28.3 (12.2) | 0.313 |
FMI, kg/m2, mean (SD) | 11.3 (3.5) | 11.2 (4.4) | 0.900 |
Total lean mass, kg, mean (SD) | 38.0 (8.0) | 41.1 (7.7) | 0.012 |
LMI, kg/m2, mean (SD) | 14.4 (2.3) | 15.9 (2.1) | <0.001 |
RSMI, kg/m2, median (IQR) | 6.1 (5.6–6.9) | 6.4 (5.9–7.3) | 0.125 |
Fat mass arms, kg, mean (SD) | 2.8 (1.2) | 2.7 (1.0) | 0.897 |
Fat mass legs, kg, mean (SD) | 9.9 (3.9) | 9.7 (4.3) | 0.822 |
Fat mass trunk, kg, mean (SD) | 14.5 (5.3) | 14.0 (7.8) | 0.729 |
Fat mass, android area, kg, median (IQR) | 2.5 (1.8–3.1) | 2.4 (1.8–3.2) | 0.740 |
Fat mass, gynoid area, kg, median (IQR) | 5.2 (3.8–6.0) | 4.9 (3.7–5.9) | 0.746 |
Lean mass arms, kg, mean (SD) | 3.9 (1.0) | 4.1 (1.1) | 0.250 |
Lean mass legs, kg, mean (SD) | 12.5 (2.6) | 12.8 (2.7) | 0.511 |
Lean mass trunk, kg, median (IQR) | 19.5 (16.7–21.7) | 19.8 (17.3–22.4) | 0.636 |
Lean mass, android area, kg, median (IQR) | 2.9 (2.5–3.4) | 2.9 (2.6–3.5) | 0.813 |
Lean mass, gynoid area, kg, mean (SD) | 5.6 (1.4) | 5.8 (1.3) | 0.569 |
Sarcopenia, n (%) | 20 (28.6) | 9 (12.9) | 0.022 |
Sarcopenic obesity, n (%) | 7 (10.0) | 1 (1.4) | 0.029 |
Sarcopenic osteoporosis, n (%) | 7 (10.0) | 3 (4.3) | 0.189 |
Physical activity and Mediterranean diet | |||
Activity by IPAQ, METs, median (IQR) | 594.0 (231.0–1386.0) | 990.0 (561.0–1993.5) | 0.033 |
MEDAS (>9), n (%) | 50 (71.4) | 60 (85.7) | 0.039 |
Adipokines and interleukins | |||
Leptin, ng/mL, median (IQR) | 159,283.7 (88,333.0–259,663.4) | 164,906.0 (82,963.6–315,133.2) | 0.518 |
Resistin, ng/mL, median (IQR) | 5263.5 (3613.2–9461.3) | 4587.6 (3182.0–6737.8) | 0.135 |
Adiponectin, µg/mL, median (IQR) | 31,555.8 (19,317.3–88,628.1) | 19,468.0 (11,361.9–42,551.7) | 0.002 |
IL-6, pg/mL, median (IQR) | 5.4 (2.2–12.3) | 1.5 (0.9–2.5) | <0.001 |
CRP, mg/L, median (IQR) | 9.4 (4.0–17.2) | 3.0 (2.0–4.0) | <0.001 |
IL-1β, pg/mL, median (IQR) | 8.2 (2.9–13.2) | 6.2 (2.3–12.3) | 0.402 |
IGF-1, pg/mL, mean (SD) | 127,919.9 (20,706.6) | 124,325.3 (15,991.6) | 0.252 |
LDL-oxidase, IU/mL, median (IQR) | 85.2 (65.5–162.2) | 62.4 (49.9–75.1) | <0.001 |
Laboratory data | |||
ESR, mm/h, median (IQR) | 24.0 (13.2–38.0) | 10.0 (6.5–16.5) | <0.001 |
Hemoglobin, g/dL, mean (SD) | 12.8 (1.4) | 13.4 (1.2) | 0.008 |
Total cholesterol, mg/dL, mean (SD) | 189.6 (33.7) | 190.5 (35.1) | 0.870 |
LDL cholesterol, mg/dL, mean (SD) | 105.5 (28.1) | 110.6 (27.3) | 0.403 |
HDL cholesterol, mg/dL, mean (SD) | 60.8 (17.4) | 59.7 (17.0) | 0.771 |
Triglycerides, mg/dL, median (IQR) | 95.0 (71.5–125.0) | 94.0 (72.0–151.5) | 0.470 |
Variable | Baseline | 6 Months | p-Value |
---|---|---|---|
Clinical characteristics | |||
DAS28-CRP, mean (SD) | 4.8 (1.1) | 3.1 (1.2) | <0.001 |
NTJ, median (IQR) | 5.5 (2.0–10.0) | 1.0 (0.0–2.0) | <0.001 |
NSJ, median (IQR) | 3.0 (1.0–6.0) | 0.0 (0.0–1.0) | <0.001 |
VAS general, mm, median (IQR) | 70 (60–90) | 10 (5–50) | <0.001 |
VAS pain, mm, median (IQR) | 70 (60–90) | 7 (2–50) | <0.001 |
VAS physician, mm, median (IQR) | 70 (60–80) | 5 (2–30) | <0.001 |
HAQ, mean (SD) | 1.3 (0.6) | 1.0 (0.6) | <0.001 |
Anthropometric characteristics | |||
BMI, kg/m2, mean (SD) | 27.8 (4.7) | 27.4 (5.2) | 0.403 |
Waist circumference, cm, mean (SD) | 95.2 (12.3) | 94.9 (10.2) | 0.760 |
Hip circumference, cm, mean (SD) | 103.8 (8.7) | 102.2 (6.7) | 0.690 |
Waist–hip ratio, mean (SD) | 0.9 (0.1) | 0.9 (0.1) | 0.880 |
Body composition by DXA | |||
Total fat mass, kg, mean (SD) | 29.1 (9.4) | 26.8 (9.5) | 0.121 |
FMI, kg/m2, mean (SD) | 11.3 (3.5) | 10.3 (3.5) | 0.243 |
Lean mass total, kg, mean (SD) | 38.0 (8.0) | 40.2 (10.5) | <0.001 |
LMI, kg/m2, mean (SD) | 14.4 (2.3) | 15.3 (3.0) | 0.016 |
RSMI, kg/m2, median, (p25-p75) | 6.1 (5.6–6.9) | 6.2 (5.8–7.1) | <0.001 |
Fat mass, arms, kg, mean (SD) | 2.8 (1.2) | 2.6 (0.9) | 0.752 |
Fat mass, legs, kg, mean (SD) | 9.9 (3.9) | 9.5 (3.6) | 0.497 |
Fat mass, trunk, kg, mean (SD) | 14.5 (5.3) | 13.8 (5.7) | 0.292 |
Fat mass, android area, kg, median (IQR) | 2.5 (1.8–3.1) | 2.4 (1.6–3.1) | 0.299 |
Fat mass, gynoid area, kg, median (IQR) | 5.2 (3.8–6.0) | 5.0 (3.7–5.7) | 0.815 |
Lean mass, arms, kg, mean (SD) | 3.9 (1.0) | 4.1 (1.2) | <0.001 |
Lean mass, legs, kg, mean (SD) | 12.5 (2.6) | 12.8 (3.3) | 0.468 |
Lean mass, trunk, kg, median (IQR) | 19.5 (16.7–21.7) | 19.8 (17.4–22.5) | 0.003 |
Lean mass, android area, kg, median (IQR) | 2.9 (2.5–3.4) | 2.9 (2.5–3.3) | 0.116 |
Lean mass, gynoid area, kg, mean (SD) | 5.6 (1.4) | 5.9 (1.3) | 0.031 |
Sarcopenia, n (%) | 20 (28.6) | 8 (11.4) | 0.004 |
Sarcopenic obesity, n (%) | 7 (10.0) | 2 (2.9) | 0.056 |
Sarcopenic osteoporosis, n (%) | 6 (8.6) | 5 (7.0) | 0.708 |
Physical activity and Mediterranean diet | |||
IPAQ activity, METs, median (IQR) | 594.0 (231.0–1386.0) | 946.5 (358.8–1640.2) | 0.0450 |
MEDAS (>9), n (%) | 50 (71.4) | 51 (72.9) | 0.784 |
Adipokines and interleukins | |||
Leptin, ng/mL, median (IQR) * | 159,283.7 (88,333.0–259,663.4) | 19,541.4 (7794.5–29,933.4) | <0.001 |
Resistin, ng/mL, median (IQR) | 5263.5 (3613.2–9461.3) | 11,076.7 (7187.8–16,763.9) | <0.001 |
Adiponectin, µg/mL, median (IQR) | 31,555.8 (19,317.3–88,628.1) | 50,807.0 (23,635.0–91,249.7) | 0.035 |
IL-6, pg/mL, median (IQR) | 5.4 (2.2–12.3) | 2.2 (1.0–6.4) | <0.001 |
PCR, mg/L, median (IQR) | 9.4 (4.0–17.2) | 1.9 (2.0–8.1) | <0.001 |
IL-1β, pg/mL, median (IQR) | 8.2 (2.9–13.2) | 3.1 (0.8–9.1) | <0.001 |
IGF-1, pg/mL, mean (SD) | 127,919.9 (20,706.6) | 137,568.6 (20,867.4) | <0.001 |
LDL-oxidase, IU/mL, median (IQR) | 85.2 (65.5–162.2) | 75.1 (54.3–131.2) | <0.001 |
Laboratory data | |||
ESR, mm/h, median (IQR) | 24.0 (13.2–38.0) | 18.5 (9.7–31.2) | 0.023 |
Hemoglobin, g/dL, mean (SD) | 12.8 (1.4) | 13.0 (1.3) | 0.029 |
Total cholesterol, mg/dL, mean (SD) | 190.5 (33.7) | 191.0 (35.0) | 0.874 |
LDL cholesterol, mg/dL, mean (SD) | 110.0 (29.1) | 117.1 (34.1) | 0.191 |
HDL cholesterol, mg/dL, mean (SD) | 63.1 (16.1) | 61.6 (17.8) | 0.364 |
Triglycerides, mg/dL, median (IQR) | 95.0 (71.5–125.0) | 91.0 (67.0–127.0) | 0.997 |
Variable | FFMI p-Pearson | Lean Mass p-Pearson | ∆ Lean Mass p-Pearson |
---|---|---|---|
Age, years | −0.052 | −0.135 | −0.103 |
Disease duration, months | 0.140 | 0.054 | −0.400 * |
Diagnostic delay, months | −0.094 | −0.024 | 0.164 |
BMI, kg/m2 | 0.505 ** | 0.314 * | −0.019 |
RF (U/mL) | 0.008 | 0.053 | −0.045 |
ACPA (U/mL) | −0.035 | −0.084 | 0.059 |
DAS28-CRP | −0.127 | −0.014 | −0.318 * |
Cumulative DAS28-CRP | −0.198 | −0.099 | −0.357 * |
HAQ | 0.017 | 0.085 | −0.323 * |
Cumulative HAQ | 0.022 | −0.004 | −0.343 * |
Activity according to IPAQ (METs) | −0.041 | −0.020 | −0.120 |
Leptin, ng/mL | 0.105 | −0.055 | −0.174 |
Resistin, ng/mL | −0.093 | −0.017 | 0.026 |
Adiponectin, µg/mL | −0.294 * | −0.280 * | 0.126 |
IL-6, pg/mL | −0.389 ** | −0.285 * | −0.060 |
CRP, mg/L | −0.234 * | −0.040 | −0.349 * |
IL-1β, pg/mL | 0.105 | 0.173 | −0.061 |
IGF-1, pg/mL | −0.310 * | −0.379 * | −0.231 |
LDL-oxidase, IU/mL | −0.070 | −0.117 | −0.053 |
ESR, mm/h | −0.377 ** | −0.237 | 0.063 |
Hemoglobin, g/dL | 0.187 | 0.206 | −0.007 |
Predictor | Univariate | Multivariate | |||
---|---|---|---|---|---|
B | 95% CI | B | 95% CI | p-Value | |
LMI * | |||||
Female sex | −2.472 | −3.848, −1.097 | −3.299 | −4.662, −1.936 | <0.001 |
Age, years | 0.005 | −0.043, 0.054 | |||
BMI | 0.270 | 0.151, 0.389 | 0.300 | 0.105, 0.416 | <0.001 |
Cumulative DAS28 | −0.278 | −0.914, 0.358 | |||
Cumulative HAQ | 0.846 | −0.035, 1.728 | |||
CRP, mg/L | −0.066 | −0.090, −0.039 | −0.063 | −0.096, −0.030 | 0.001 |
Adiponectin | −1.632 | −3.074, −0.191 | |||
Leptin | 1.352 | 0.145, 3.849 | |||
METs | 0.220 | −1.519, 1.958 | |||
Lean mass ** | |||||
Female sex | −13.115 | −17.088, −9.141 | −13.288 | −17.598, −8.978 | <0.001 |
Age, years | −0.088 | −0.253, 0.078 | |||
BMI | 0.575 | 0.126, 1.025 | 0.560 | 0.186, 0.934 | 0.004 |
Cumulative DAS28 | −0.837 | −3.034, 1.360 | |||
Cumulative HAQ | 1.019 | −2.093, 4.131 | |||
CRP, mg/L | −0.098 | −0.214, −0.018 | −0.151 | −0.258, −0.044 | 0.007 |
Adiponectin | −6.679 | −11.575, 1.783 | |||
Leptin | −1.519 | −6.657, 3.619 | |||
METs | 1.112 | −4.333, 6.557 | |||
∆ lean mass ¥ | |||||
Female sex | −3.891 | −8.405, 0.623 | |||
Age, years | −0.060 | −0.225, 0.106 | |||
BMI | −0.031 | −0.500, 0.437 | |||
Cumulative DAS28 | −2.295 | −4.179, −0.410 | −2.578 | −4.963, −0.193 | 0.035 |
Cumulative HAQ | −3.343 | −6.218, −0.469 | |||
CRP, mg/L | −0.153 | −0.271, −0.035 | −0.198 | −0.322, −0.074 | 0.003 |
Adiponectin | −1.144 | −7.165, 4.877 | |||
Leptin | −3.624 | −8.077, 0.828 | |||
METs | −1.144 | −7.165, 4.877 |
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Mena-Vázquez, N.; García-Studer, A.; Ortiz-Márquez, F.; Manrique-Arija, S.; Mucientes, A.; Lisbona-Montañez, J.M.; Borregón-Garrido, P.; Ruiz-Limón, P.; Redondo-Rodriguez, R.; Cano-García, L.; et al. Longitudinal Assessment of Body Composition and Inflammatory Status in Rheumatoid Arthritis During TNF Inhibitor Treatment: A Pilot Study. Int. J. Mol. Sci. 2025, 26, 7635. https://doi.org/10.3390/ijms26157635
Mena-Vázquez N, García-Studer A, Ortiz-Márquez F, Manrique-Arija S, Mucientes A, Lisbona-Montañez JM, Borregón-Garrido P, Ruiz-Limón P, Redondo-Rodriguez R, Cano-García L, et al. Longitudinal Assessment of Body Composition and Inflammatory Status in Rheumatoid Arthritis During TNF Inhibitor Treatment: A Pilot Study. International Journal of Molecular Sciences. 2025; 26(15):7635. https://doi.org/10.3390/ijms26157635
Chicago/Turabian StyleMena-Vázquez, Natalia, Aimara García-Studer, Fernando Ortiz-Márquez, Sara Manrique-Arija, Arkaitz Mucientes, Jose Manuel Lisbona-Montañez, Paula Borregón-Garrido, Patricia Ruiz-Limón, Rocío Redondo-Rodriguez, Laura Cano-García, and et al. 2025. "Longitudinal Assessment of Body Composition and Inflammatory Status in Rheumatoid Arthritis During TNF Inhibitor Treatment: A Pilot Study" International Journal of Molecular Sciences 26, no. 15: 7635. https://doi.org/10.3390/ijms26157635
APA StyleMena-Vázquez, N., García-Studer, A., Ortiz-Márquez, F., Manrique-Arija, S., Mucientes, A., Lisbona-Montañez, J. M., Borregón-Garrido, P., Ruiz-Limón, P., Redondo-Rodriguez, R., Cano-García, L., & Fernández-Nebro, A. (2025). Longitudinal Assessment of Body Composition and Inflammatory Status in Rheumatoid Arthritis During TNF Inhibitor Treatment: A Pilot Study. International Journal of Molecular Sciences, 26(15), 7635. https://doi.org/10.3390/ijms26157635