Session Information
Date: Sunday, November 5, 2017
Title: Rheumatoid Arthritis – Clinical Aspects Poster I: Treatment Patterns and Response
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Methotrexate (MTX) is the first line treatment for patients with rheumatoid arthritis (RA). For over 30% of patients, MTX fails to diminish DAS28 score in a timely and satisfactory manner. The challenge is to find a way to identify these non-responders at the time of diagnosis. The aims of this study were to determine whether plasma cytokines could be used as biomarkers of early RA and of therapeutic response to MTX.
Methods: Thirty RA patients receiving MTX (mean age 58 ± 12 y.o. with symptom duration of 6 ± 3 mo.) from the Group for Early Arthritis Research (GEAR) / CHU de Québec SARD Biobank Data Repository (SBDR). Patients were evaluated clinically at baseline and 6 mo., and classified as responders to MTX or non-responders according to the DAS28CRP EULAR Classification (good response vs moderate/none). Plasma cytokines were measured at baseline by multiplex assay or ELISA and compared to age- and sex-matched healthy controls. Patients were Bivariate logistic regression was used to identify RA patients and non-responders based on cytokine concentration or detection, with Firth bias correction when needed. Optimal cut points were found using distance criteria and their predictive performance was assessed.
Results: Plasma concentrations of IL-1RA, CCL11/Eotaxin, CXCL10/IP-10, CCL2/MCP-1, CCL4/MIP-1β, CCL5/RANTES, CXCL12a/SDF-1α and calprotectin were significantly different in RA patients compared to controls. IL-21, IL-22, IL-1α, CXCL1/GROα were detected differently in RA plasma (Table 1). IL-1RA and CCL4/MIP-1β were good predictors of RA with sensitivity and specificity of approximately 95% when dichotomized with cut points of 280 and 124, respectively. Thirty-five percent of patients were non-responders to MTX. IL-1α, IL-18, IL-17A and IL-27 were less frequently detected in non-responders (Table 2).
Conclusion: Several cytokines differentially expressed in plasma are associated with early RA. Absence of detection of IL-1α, IL-17A and IL-27 and low concentration of IL-18 was associated with non-response to MTX. We propose that these cytokines could be used as predictors of MTX response in RA.
Acknowledgements: This work was partly funded by CIHR. We thank Pfizer, Amgen, BMS, Abbvie, Roche, Sanofi-Genzyme and Merck & Co. for unrestricted financial contribution to the SBDR.
Table 1: Plasma cytokine concentrations significantly different between RA patients and healthy controls at baseline.
|
Cytokine |
Controls (n=30) |
RA (n=30) |
Odds Ratios (95% CI) |
Pvalue (Wald) |
|
IL-1RA |
92 (56-174) |
1561 (1175-2607) |
1.01(1.00-1.01) |
0.0065 |
|
CCL11/Eotaxin |
23 (17-33) |
32 (25-38) |
1.08(1.02-1.15) |
0.0083 |
|
CXCL10/IP-10 |
10 (8-12) |
30 (23-47) |
1.30(1.16-1.52) |
<0.0001 |
|
CCL2/MCP-1 |
19 (15-27) |
37 (26-49) |
1.07(1.03-1.13) |
0.0034 |
|
CCL4/MIP-1β |
22 (19-27) |
180 (166-209) |
1.03(1.02-1.05) |
<0.0001 |
|
CCL5/RANTES |
24 (20-27) |
56 (42-67) |
1.04(1.01-1.07) |
0.0075 |
|
CXCL12a/SDF-1α |
396 (349-423) |
629 (482-754) |
1.01(1.00-1.02) |
0.0010 |
|
Calprotectin |
1398 (1082-1915) |
2675 (2171-3968) |
1.00(1.00-1.00) |
0.0006 |
|
IL-21 |
3(10) |
11(37) |
5.21(1.41-25.39) |
0.0213 |
|
IL-22 |
14 (47) |
1(3) |
0.04(0.00-0.22) |
0.0028 |
|
IL-1α |
6(20) |
16(53) |
4.57(1.51-15.35) |
0.0094 |
|
CXCL1/GRO-α |
25(83) |
4(13) |
0.03(0.01-0.12) |
<0.0001 |
Values are presented as median in pg/ml (Quartile 1 – Quartile 3) or N(%)
Table 2: Plasma cytokines less frequently detected in RA patients non-responding to MTX
|
Cytokine |
Responders (N=19) |
Non-responders (N=10) |
Odds Ratios (95% CI) |
P-value (Wald) |
|
IL-18 |
24 (15-30) |
16 (0-20) |
0.93 (0.86-1.00) |
0.0745 |
|
IL-1α |
13(68) |
2(20) |
0.12 (0.01-0.63) |
0.0205 |
|
IL-17A |
7(37) |
0(0) |
0.08 (0.00-0.79) |
0.12 |
|
IL-27 |
7(37) |
0(0) |
0.08 (0.00-0.79) |
0.12 |
Values are presented as median in pg/ml (Quartile 1 – Quartile 3) or N(%)
To cite this abstract in AMA style:
Pelletier M, Fortin PR, Longchamps MP, Parent G, Benk-Fortin H, Julien AS, Amiable N, Rollet-Labelle E, Michou L, Bessette L, Tessier PA. Plasma Cytokines at Diagnosis May Predict Non-Response to Methotrexate in Patients with Early Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/plasma-cytokines-at-diagnosis-may-predict-non-response-to-methotrexate-in-patients-with-early-rheumatoid-arthritis/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasma-cytokines-at-diagnosis-may-predict-non-response-to-methotrexate-in-patients-with-early-rheumatoid-arthritis/