ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1445

Effect of Methotrexate (MTX), and MTX Plus Colchicine (CCH) on the Expression and Activity of NLRP3 Inflammasome in Patients with Early Rheumatoid Arthritis (RA)

Dolores Ramos-Bello1, Crisol Alvarez-Quiroga2, Georgina Aguilera Barragán-Pickens3, Angel Javier Pedro Martínez3, Tania Adriana Luna-Zúñiga3, Georgina Martínez-Flores3, Eduardo Saul Acevedo-Castañeda4, Homero López-Ferretis3, Enrique Cuevas-Orta3, Eva Santillan-Guerrero3, Ricardo Moreno-Valdez3, Martín Saldaña-Baarnard3, Marco Ulises Martinez-Martinez5, David Herrera Van Oostdam6, Roberto González-Amaro7 and Carlos Abud-Mendoza8, 1Reumatología, Unidad Regional de Reumatologia y Osteoporosis Hospital Central "Dr. Ignacio Morones Prieto" y Facultad de Medicina de la UASLP, San Luis Potosi, Mexico, 2División de Medicina Molecular y Traslacional, Centro de Investigación en Ciencias de la Salud y Biomedicina, UASLP, San Luis Potosí, Mexico, 3Unidad Regional de Reumatologia y Osteoporosis Hospital Central "Dr. Ignacio Morones Prieto" y Facultad de Medicina de la UASLP, San Luis Potosí, Mexico, 4Medicina Interna, Unidad Regional de Reumatologia y Osteoporosis Hospital Central "Dr. Ignacio Morones Prieto" y Facultad de Medicina de la UASLP, San Luis Potosí, Mexico, 5Unidad de Investigaciones Reumatológicas, Faculty of Medicine, Universidad Autónoma de San Luis Potosí and Hospital Central, San Luis Potosí, Mexico, 6Unidad de Investigaciones Reumatológicas, Hospital Central & Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico, 7Inmunología, Facultad de Medicina de la UASLP, San Luis Potosí, Mexico, 8Unidad de Investigaciones Reumatológicas y Osteoporosis, Faculty of Medicine, Universidad Autónoma de San Luis Potosí and Hospital Central, San Luis Potosí, Mexico

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: , , , ,

Session Information

Date: Monday, November 6, 2017

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy Poster II: Prognostic Factors, Imaging and Miscellaneous Reports

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: NLRP3 inflammasome is an intracellular protein complex involved in the production of pro-inflammatory cytokines as IL-1β and IL-18, which has been reported to have a role in the pathogenesis of RA. Since CCH is a potent inhibitor of NLRP3, we hypothesized that it may significantly modify the expression and function of this molecular complex, reducing the inflammatory phenomenon in RA. Accordingly, the aim of this study was to evaluate the possible effect of CCH administration on the expression and activity of NLRP3 in patients with early RA.

Methods:  We selected consecutive patients with RA according to the ACR/EULAR 2010 criteria with ≤12 months of evolution and were randomly assigned to 2 groups: MTX (15 mg/week); or MTX (15 mg/week) plus CCH (1.5 mg/day). Inflammasome expression by monocytes was assessed by two-color flow cytometry (CD14+NLRP3+ cells), and its function was estimated through the analysis of Caspase-1 activity (colorimetric assay). Clinical activity was assessed by HAQ-DI, CDAI, SDAI and DAS28-ESR at 0, 1 and 3 months.

Results : Twenty DMARD naive patients have been recruited, their main characteristics are shown in table 1. In a preliminary analysis of 7 patients in the MTX group and 6 patients in the MTX+CCH group after 1 month of treatment, and 3 patients in the MTX group and 4 patients in the MTX+CCH group after 3 months of treatment, all patients had increased levels of caspase-1 activity and NLRP3; patients in the MTX group had a significant change in its expression at 1 month (Table 2), however that difference was not subsequently detected at month 3. In contrast, patients in the MTX+CCH group showed a significant decrease in the expression and activity of NLRP3 at 1 and 3 months (p<0.05). Moreover, a significant improvement in clinical parameters was observed in both at months 1 and 3. We will present follow-up all patients.

Conclusion: Our preliminary data suggest that CCH administration is associated with sustained decrease in the expression and activity of the NLRP3 inflammasome. This phenomenon might contribute to decrease inflammation and may help to achieve low disease activity.

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Disclosure: D. Ramos-Bello, None; C. Alvarez-Quiroga, None; G. Aguilera Barragán-Pickens, None; A. J. Pedro Martínez, None; T. A. Luna-Zúñiga, None; G. Martínez-Flores, None; E. S. Acevedo-Castañeda, None; H. López-Ferretis, None; E. Cuevas-Orta, None; E. Santillan-Guerrero, None; R. Moreno-Valdez, None; M. Saldaña-Baarnard, None; M. U. Martinez-Martinez, None; D. Herrera Van Oostdam, None; R. González-Amaro, None; C. Abud-Mendoza, Bristol-Myers Squibb, Pfizer Inc, Roche, 5,Bristol-Myers Squibb, Merck-Serono, Pfizer Inc, Roche, UCB, 8.

To cite this abstract in AMA style:

Ramos-Bello D, Alvarez-Quiroga C, Aguilera Barragán-Pickens G, Pedro Martínez AJ, Luna-Zúñiga TA, Martínez-Flores G, Acevedo-Castañeda ES, López-Ferretis H, Cuevas-Orta E, Santillan-Guerrero E, Moreno-Valdez R, Saldaña-Baarnard M, Martinez-Martinez MU, Herrera Van Oostdam D, González-Amaro R, Abud-Mendoza C. Effect of Methotrexate (MTX), and MTX Plus Colchicine (CCH) on the Expression and Activity of NLRP3 Inflammasome in Patients with Early Rheumatoid Arthritis (RA) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/effect-of-methotrexate-mtx-and-mtx-plus-colchicine-cch-on-the-expression-and-activity-of-nlrp3-inflammasome-in-patients-with-early-rheumatoid-arthritis-ra/. Accessed .

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