Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1
Abstract
1. Introduction
2. Results
2.1. Association of Biomarkers with DAS28-Related Scores, Tender Joint Count, and Swollen Joint Count
2.2. Expression of Joint Swelling in Different DAS28-Based Remission Criteria
2.3. Fulfillment of Two Remission Definitions by Different DAS28-Based Remission Criteria, Together with Medication Changes
3. Discussion
4. Materials and Methods
4.1. Participants and Study Design
4.2. Calculation of DAS28 Scores
4.3. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Aletaha, D.; Landewe, R.; Karonitsch, T.; Bathon, J.; Boers, M.; Bombardier, C.; Bombardieri, S.; Choi, H.; Combe, B.; Dougados, M.; et al. Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Ann. Rheum. Dis. 2008, 67, 1360–1364. [Google Scholar] [CrossRef] [PubMed]
- Felson, D.T.; Smolen, J.S.; Wells, G.; Zhang, B.; van Tuyl, L.H.; Funovits, J.; Aletaha, D.; Allaart, C.F.; Bathon, J.; Bombardieri, S.; et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011, 63, 573–586. [Google Scholar] [CrossRef] [PubMed]
- Thiele, K.; Huscher, D.; Bischoff, S.; Späthling-Mestekemper, S.; Backhaus, M.; Aringer, M.; Kohlmann, T.; Zink, A. Performance of the 2011 ACR/EULAR preliminary remission criteria compared with DAS28 remission in unselected patients with rheumatoid arthritis. Ann. Rheum. Dis. 2013, 72, 1194–1199. [Google Scholar] [CrossRef] [PubMed]
- Pinals, R.S.; Masi, A.T.; Larsen, R.A. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum. 1981, 24, 1308–1315. [Google Scholar] [CrossRef]
- Chandrashekara, S.; Priyanka, B.U. Remission in rheumatoid arthritis by different criteria does not converge over the inflammatory markers. Int. J. Rheum. Dis. 2013, 16, 291–296. [Google Scholar] [CrossRef]
- Aletaha, D.; Smolen, J.S. Remission in rheumatoid arthritis: Missing objectives by using inadequate DAS28 targets. Nat. Rev. Rheumatol. 2019, 15, 633–634. [Google Scholar] [CrossRef]
- Schoels, M.; Alasti, F.; Smolen, J.S.; Aletaha, D. Evaluation of newly proposed remission cut-points for disease activity score in 28 joints (DAS28) in rheumatoid arthritis patients upon IL-6 pathway inhibition. Arthritis Res. Ther. 2017, 19, 155. [Google Scholar] [CrossRef]
- Orange, D.E.; Agius, P.; DiCarlo, E.F.; Mirza, S.Z.; Pannellini, T.; Szymonifka, J.; Jiang, C.S.; Figgie, M.P.; Frank, M.O.; Robinson, W.H.; et al. Histologic and Transcriptional Evidence of Subclinical Synovial Inflammation in Patients with Rheumatoid Arthritis in Clinical Remission. Arthritis Rheumatol. 2019, 71, 1034–1041. [Google Scholar] [CrossRef]
- Liou, L.B.; Tsai, W.P.; Chang, C.J.; Chao, W.J.; Chen, M.H. Blood monocyte chemotactic protein-1 (MCP-1) and adapted disease activity Score28-MCP-1: Favorable indicators for rheumatoid arthritis activity. PLoS ONE 2013, 8, e55346. [Google Scholar] [CrossRef]
- Liou, L.B.; Fang, Y.F.; Tan, C.F.; Lai, J.H.; Jang, S.S.; Tsai, P.H.; Yeh, T.C. A new laboratory surrogate (Monocyte Chemotactic Protein-1) for Disease Activity Score28: A favourable indicator for remission in rheumatoid arthritis. Sci. Rep. 2020, 10, 8238. [Google Scholar] [CrossRef]
- Rollins, B.J. Monocyte chemoattractant protein 1: A potential regulator of monocyte recruitment in inflammatory disease. Mol. Med. Today 1996, 2, 198–204. [Google Scholar] [CrossRef] [PubMed]
- Bilgic, H.; Ytterberg, S.R.; Amin, S.; McNallan, K.T.; Wilson, J.C.; Koeuth, T.; Ellingson, S.; Newman, B.; Bauer, J.W.; Peterson, E.J.; et al. Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum. 2009, 60, 3436–3446. [Google Scholar] [CrossRef] [PubMed]
- Gschwandtner, M.; Derler, R.; Midwood, K.S. More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis. Front. Immunol. 2019, 10, 2759. [Google Scholar] [CrossRef] [PubMed]
- Morrison, N.A.; Day, C.J.; Nicholson, G.C. Dominant negative MCP-1 blocks human osteoclast differentiation. J. Cell. Biochem. 2014, 115, 303–312. [Google Scholar] [CrossRef] [PubMed]
- Villiger, P.M.; Terkeltaub, R.; Lotz, M. Monocyte chemoattractant protein-1 (MCP-1) expression in human articular cartilage. Induction by peptide regulatory factors and differential effects of dexamethasone and retinoic acid. J. Clin. Investig. 1992, 90, 488–496. [Google Scholar] [CrossRef]
- Lisignoli, G.; Toneguzzi, S.; Pozzi, C.; Piacentini, A.; Grassi, F.; Ferruzzi, A.; Gualtieri, G.; Facchini, A. Chemokine expression by subchondral bone marrow stromal cells isolated from osteoarthritis (OA) and rheumatoid arthritis (RA) patients. Clin. Exp. Immunol. 1999, 116, 371–378. [Google Scholar] [CrossRef]
- Gong, J.H.; Ratkay, L.G.; Waterfield, J.D.; Clark-Lewis, I. An antagonist of monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model. J. Exp. Med. 1997, 186, 131–137. [Google Scholar] [CrossRef]
- Mäkinen, H.; Kautiainen, H.; Hannonen, P.; Sokka, T. Is DAS28 an appropriate tool to assess remission in rheumatoid arthritis? Ann. Rheum. Dis. 2005, 64, 1410–1413. [Google Scholar] [CrossRef]
- Felson, D.; Lacaille, D.; LaValley, M.P.; Aletaha, D. Reexamining remission definitions in rheumatoid arthritis: Considering the twenty-eight-joint Disease Activity Score, C-reactive protein level and patient global assessment. RMD Open 2021, 7, e002034. [Google Scholar] [CrossRef]
- Smolen, J.S.; Breedveld, F.C.; Burmester, G.R.; Bykerk, V.; Dougados, M.; Emery, P.; Kvien, T.K.; Navarro-Compán, M.V.; Oliver, S.; Schoels, M.; et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann. Rheum. Dis. 2016, 75, 3–15. [Google Scholar] [CrossRef]
- Calabrò, A.; Caterino, A.L.; Elefante, E.; Valentini, V.; Vitale, A.; Talarico, R.; Cantarini, L.; Frediani, B. One year in review 2016: Novelties in the treatment of rheumatoid arthritis. Clin. Exp. Rheumatol. 2016, 34, 357–372. [Google Scholar] [PubMed]
- Kalyoncu, U.; Dougados, M.; Daurès, J.P.; Gossec, L. Reporting of patient-reported outcomes in recent trials in rheumatoid arthritis: A systematic literature review. Ann. Rheum. Dis. 2009, 68, 183–190. [Google Scholar] [CrossRef] [PubMed]
- Boubouchairopoulou, N.; Flouri, I.; Drosos, A.A.; Boki, K.; Settas, L.; Zisopoulos, D.; Skopouli, F.N.; Papadopoulos, I.; Iliopoulos, A.; Kyriopoulos, J.; et al. Treatment with the first TNF inhibitor in rheumatoid arthritis patients in the Hellenic Registry of Biologic Therapies improves quality of life especially in young patients with better baseline functional status. Clin. Exp. Rheumatol. 2016, 34, 999–1005. [Google Scholar] [PubMed]
- Ma, M.H.Y.; Ibrahim, F.; Kingsley, G.H.; Cope, A.; Scott, D.L. Variable impacts of different remission states on health-related quality of life in rheumatoid arthritis. Clin. Exp. Rheumatol. 2018, 36, 203–209. [Google Scholar] [PubMed]
- Carvalho, P.D.; Ferreira, R.J.O.; Landewé, R.; Vega-Morales, D.; Salomon-Escoto, K.; Veale, D.J.; Chopra, A.; da Silva, J.A.P.; Machado, P.M. Association of 17 Definitions of Remission with Functional Status in a Large Clinical Practice Cohort of Patients with Rheumatoid Arthritis. J. Rheumatol. 2020, 47, 20–27. [Google Scholar] [CrossRef]
- Liou, L.B.; Fang, Y.F.; Tsai, P.H.; Chen, Y.F.; Chang, C.T.; Chen, C.C.; Chiang, W.Y. Immunoregulatory Cells and Cytokines Discriminate Disease Activity Score 28-Remission Statuses and Ultrasound Grades in Rheumatoid Arthritis Patients with Non-High Disease Activity. Int. J. Mol. Sci. 2024, 25, 8694. [Google Scholar] [CrossRef]
- van der Heijde, D.M.; van‘t Hof, M.A.; van Riel, P.L.; Theunisse, L.A.; Lubberts, E.W.; van Leeuwen, M.A.; van Rijswijk, M.H.; van de Putte, L.B. Judging disease activity in clinical practice in rheumatoid arthritis: First step in the development of a disease activity score. Ann. Rheum. Dis. 1990, 49, 916–920. [Google Scholar] [CrossRef]
- Prevoo, M.L.; van‘t Hof, M.A.; Kuper, H.H.; van Leeuwen, M.A.; van de Putte, L.B.; van Riel, P.L. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995, 38, 44–48. [Google Scholar] [CrossRef]
- Aletaha, D.; Nell, V.P.; Stamm, T.; Uffmann, M.; Pflugbeil, S.; Machold, K.; Smolen, J.S. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: Validation of a clinical activity score. Arthritis Res. Ther. 2005, 7, R796–R806. [Google Scholar] [CrossRef]
- Available online: https://www.psychometrica.de/correlation (accessed on 20 January 2018).
The 2013 Cohort | The 2020 Cohort | |||
---|---|---|---|---|
Variables | Mean ± S.D. or Median | Range or Inter-Quartile Ranges (25th, 75th) | Mean ± S.D. or Median | Range or Inter-Quartile Ranges (25th, 75th) |
Number of patients | 111 | F:M = 4.05:1 (89:22) | 178 | F:M = 3.94:1 (142:36) |
Total visits in 12 months | - | - | 835 | - |
ESR (mm/h) | 41.29 ± 28.56 | 4–128 | 17.50 | (9.75–36.00) |
CRP (mg/L) | 10.10 | (3.30–28.60) | 3.90 | (0.24–133.15) |
MCP-1 (pg/mL) | 58.63 | (31.5–160.35) | 101.8 | (73.6–140.1) |
Tender joint count | 6.7 ± 5.5 | 0–28 | 5.0 | (2.0, 9.3) |
Swollen joint count | 4.0 | (1.0, 7.0) | 2.0 | (1.0, 5.3) |
DAS28-ESR scores | 5.2 ± 1.6 | 1.6–8.6 | 4.3 ± 1.4 | 0.8–7.3 |
DAS28-CRP scores | 4.7 ± 1.6 | 1.5–7.9 | 4.8 ± 1.3 | 2.5–8.3 |
SDAI | - | - | 15.3 | (9.1, 23.7) |
CDAI | - | - | 10.0 | (5.0, 17.0) |
DAS28-MCP-1 scores | 4.9 ± 1.6 | 2.4–9.9 | 4.2 ± 1.0 | 2.2–6.8 |
Dependent Variables | Independent Variables | t-Values | p-Values |
---|---|---|---|
DAS28-ESR scores | |||
ESR | 5.640 | <0.001 | |
CRP | 0.883 | 0.407 | |
MCP-1 | 2.987 | 0.003 | |
DAS28-CRP scores | |||
ESR | 0.587 | 0.559 | |
CRP | 4.390 | <0.001 | |
MCP-1 | 2.513 | 0.013 | |
DAS28-MCP-1 scores | |||
ESR | 1.953 | 0.053 | |
CRP | 1.457 | 0.148 | |
MCP-1 | 0.618 | <0.001 |
Dependent Variables | Independent Variables | t-Values | p-Values |
---|---|---|---|
DAS28-ESR scores | |||
ESR | 13.642 | <0.001 | |
CRP | 2.650 | 0.008 | |
MCP-1 | 2.343 | 0.019 | |
DAS28-CRP scores | |||
ESR | 3.314 | 0.001 | |
CRP | 9.842 | <0.001 | |
MCP-1 | 2.283 | 0.023 | |
SDAI | |||
ESR | 0.949 | 0.343 | |
CRP | 6.936 | <0.001 | |
MCP-1 | 2.441 | 0.015 | |
CDAI | |||
ESR | 0.989 | 0.323 | |
CRP | 3.839 | <0.001 | |
MCP-1 | 2.465 | 0.014 | |
DAS28-MCP-1 scores | |||
ESR | 2.001 | 0.046 | |
CRP | 3.684 | <0.001 | |
MCP-1 | 7.196 | <0.001 |
Dependent Variables | Independent Variables | t-Values | p-Values |
---|---|---|---|
TJC (the 2013 cohort) | |||
ESR | 1.226 | 0.223 | |
CRP | 0.610 | 0.543 | |
MCP-1 | 2.987 | 0.003 | |
TJC (the 2020 cohort) | |||
ESR | 0.605 | 0.545 | |
CRP | 3.256 | 0.001 | |
MCP-1 | 2.161 | 0.031 | |
SJC (the 2013 cohort) | |||
ESR | 2.641 | 0.010 | |
CRP | 1.929 | 0.056 | |
MCP-1 | 3.423 | 0.001 | |
SJC (the 2020 cohort) | |||
ESR | 0.829 | 0.407 | |
CRP | 6.718 | <0.001 | |
MCP-1 | 4.322 | <0.001 |
The Remaining SJC Based on Individual Patients | The Remaining SJC Based on Patient Visits | The Remaining SJC ≧ 2 Based on Patient Visits | |
---|---|---|---|
DAS28-ESR (<2.6) | 38.7/26 = 1.49 ± 1.92 (reference) | 62/38 = 1.63 ± 1.57 (reference) | 36/12 = 3.00 ± 2.30 (reference) |
DAS28-CRP (<2.5) | 2.5/2 = 1.25 ± 1.06 (p = 0.806) | 3/2= 1.50 ± 0.71 (p = 0.841) | 2/1 = 2.00 (p = 0.684) |
SDAI (≦3.3) | 6.3/9 = 0.71 ± 0.56 (p = 0.07) | 11/9 = 1.22 ± 0.44 (p = 0.170) | 4/2 = 2.00 ± 0.00 (p = 0.160) |
CDAI (≦2.8) | 7.8/11 = 0.72 ± 0.51 (p = 0.07) | 14/11 = 1.27 ± 0.47 (p = 0.223) | 6/3 = 2.00 ± 0.00 (p = 0.160) |
DAS28-MCP-1 (<2.2) | 4.5/4 = 1.13 ± 0.63 (p = 0.466) | 6/4 = 1.50 ± 0.58 (p = 0.740) | 4/2 = 2.00 ± 0.00 (p = 0.160) |
Remission Status | Odds Ratio a | The Remission Group (%): Dose Change or a New Drug | The Non-Remission Group (%): Dose Change or a New Drug | |
---|---|---|---|---|
Fulfilled the 2005 modified ARA remission b | ||||
DAS28-ESR (<2.6) | 36.99% (64/173) | Reference | 2/22 = 9.09% | 17/56 = 30.36% |
DAS28-CRP (<2.5) | 70.00% (49/70) | 3.97 | 2/18 = 11.11% | 2/7 = 28.57% |
SDAI (≦3.3) | 54.10% (66/122) | 2.01 | 2/22 = 9.09% | 2/24 = 8.33% |
CDAI (≦2.8) | 53.33% (64/120) | 1.44 | 2/22 = 9.09% | 2/23 = 8.70% |
DAS28-MCP-1 (<2.2) | 75.61% (61/82) | 5.28 | 2/21= 9.52% | 0/5 = 0.00% |
Fulfilled the 2011 ACR/EULAR remission c | ||||
DAS28-ESR (<2.6) | 49.13% (85/173) | Reference | 2/30 = 6.67% * | 17/48 = 35.42% * |
DAS28-CRP (<2.5) | 82.86% (58/70) | 5.00 | 2/21 = 9.52% | 2/4 = 50.00% |
SDAI (≦3.3) | 81.97% (100/122) | 4.71 | 4/38 = 10.52% | 0/8 = 0.00% |
CDAI (≦2.8) | 80.83% (97/120) | 1.65 | 4/38 = 10.52% | 0/7 = 0.00% |
DAS28-MCP-1 (<2.2) | 81.71% (67/82) | 4.62 | 2/23 = 8.70% | 0/3 = 0.00% |
Measures | M0 (n = 178) Correlation Coefficients (p-Values against the Reference) | M3 (n = 163) Correlation Coefficients (p-Values against the Reference) | M6 (n = 163) Correlation Coefficients (p-Values against the Reference) | M9 (n = 162) Correlation Coefficients (p-Values against the Reference) | M12 (n = 169) Correlation Coefficients (p-Values against the Reference) |
---|---|---|---|---|---|
DAS28-ESR | 0.553 (reference) | 0.486 (reference) | 0.607 (reference) | 0.603 (reference) | 0.524 (reference) |
DAS28-CRP | 0.626 (0.002) * | 0.526 (0.094) | 0.627 (0.216) | 0.690 (0.001) * | 0.593 (0.009) * |
SDAI | 0.650 (<0.001) * | 0.541 (0.071) | 0.686 (0.015) * | 0.697 (0.003) * | 0.633 (0.001) * |
CDAI | 0.639 (0.003) * | 0.550 (0.059) | 0.681 (0.029) * | 0.677 (0.024) * | 0.634 (0.002) * |
DAS28-MCP-1 | 0.564 (0.372) | 0.522 (0.172) | 0.650 (0.086) | 0.647 (0.112) | 0.583 (0.059) |
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Tsai, P.-H.; Liou, L.-B. Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1. Int. J. Mol. Sci. 2024, 25, 11374. https://doi.org/10.3390/ijms252111374
Tsai P-H, Liou L-B. Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1. International Journal of Molecular Sciences. 2024; 25(21):11374. https://doi.org/10.3390/ijms252111374
Chicago/Turabian StyleTsai, Ping-Han, and Lieh-Bang Liou. 2024. "Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1" International Journal of Molecular Sciences 25, no. 21: 11374. https://doi.org/10.3390/ijms252111374
APA StyleTsai, P.-H., & Liou, L.-B. (2024). Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1. International Journal of Molecular Sciences, 25(21), 11374. https://doi.org/10.3390/ijms252111374