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POS0292 (2022)
INCREASE OF PRO-INFLAMMATORY CYTOKINES IS ASSOCIATED WITH ANTI-IDIOTYPE EVENTS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH INFLIXIMAB OR ADALIMUMAB
D. X. Xibille Friedmann1, S. M. Carrillo Vazquez2, J. González Christen3, D. Vega Morales4, M. Garza Elizondo4, R. Hernández5, J. E. Ortíz Panozo6, J. L. Montiel Hernández3
1Hospital General de Cuernavaca, Rheumatology, Cuernavaca, Mexico
2Hospital Regional 1 de Octubre, Rheumatology, CDMX, Mexico
3Universidad Autónoma del Estado de Morelos, Facultad de Farmacia, Cuernavaca, Mexico
4Universidad Autónoma de Nuevo León, Rheumatology, Monterrey, Mexico
5Hospital de Especialidades, Centro Médico NAcional S. XXI, Rheumatology, CDMX, Mexico
6Instituto Nacional de Salud Pública, Epidemiology, Cuernavaca, Mexico

Background: A significant percentage of rheumatoid arthritis (RA) patients undergoing Infliximab (IFX) or Adalimumab (ADA) treatment develop antidrug antibodies with potential negative effects over their clinical activity; however, it is unknown if these anti-idiotype events could be associated with changes in cytokines levels


Objectives: To evaluate the association between blood cytokine levels, anti-idiotype events and clinical activity in RA patients treated with IFX or ADA.


Methods: All patients complied with ACR/EULAR 2021 criteria for RA and received anti-TNFa agents. Blood samples were collected during the drug trough and kept at -75ºC until analysis. Clinical activity was based on DAS28-ESR. Specific anti-drug antibodies to IFX and ADA were evaluated by sandwich ELISA. Cytokine blood levels were quantified using a multiplex system or sandwich ELISA.


Results: 57 patients with RA were recruited, 17 treated with IFX and 40 with ADA. According to the presence of anti-drug antibodies and sub-optimal levels of the biologic drug, patients were classified as immunogenic (29.8%; n=17) and non-immunogenic (70.2%; n=40), the first showed significantly higher ESR (p<0.001) and DAS28 (p<0.005). A significant association was seen between antidrug antibodies and increases of IFNg (2.1 OR, CI95%:1.2-3.8, p<0.01); MCP-1 (3.9 OR, CI95%:1.1-14.5, p<0.05); MIF (2.8 OR, CI95%:1.3-5.7, p<0.01) and TNFa 3.0 OR, CI95%:1.3-6.6, p<0.01 (see Table 1 ). Although anti-idiotype events were more frequent in IFX treated patients (41%), a significant difference was not seen when comparing with ADA treated patients (25%).

Association analysis between anti-Idiotype events with cytokine levels.

Anti-Idiotype events vs Crude results OR (IC, 95%) p Model 1* OR (IC, 95%) p Model 2** OR (IC, 95%) p
IL-1β 2.04 (1.26-3.30 ) 0.004 2.18 (1.27-3.74 ) 0.005 2.72 (1.41-5.24 ) 0.003
IL-6 1.29 (1.02-1.64 ) 0.03 1.30 (1.00-1.69 ) 0.04 1.33 (1.03-1.72 ) 0.02
IL-8 1.20 (0.80-1.79) 0.37 1.24 (0.81-1.88) 0.32 1.22 (0.79-1.90) 0.35
IL-10 1.18 (0.91-1.51) 0.20 1.16 (0.89-1.53) 0.26 1.22 (0.92-1.62) 0.15
IL-12p40 1.73 (1.09-2.76 ) 0.02 1.67 (1.00-2.80 ) 0.04 1.90 (1.12-3.22 ) 0.01
IL-17A 1.39 (0.95-2.02) 0.08 1.31 (0.90-1.91) 0.15 1.51 (1.01-2.25 ) 0.04
INF ϒ 2.38 (1.37-4.12 ) 0.002 2.36 (1.32-4.23 ) 0.004 2.97 (1.57-5.61 ) 0.001
Leptina 6.15 (0.77-48.72) 0.09 4.79 (0.63-1.07) 0.12 7.30 (0.78-68.37) 0.08
MIF 3.94 (1.07-14.48 ) 0.04 5.86 (1.28-26.65 ) 0.02 3.45 (0.87-13.68) 0.07
MCP-1 2.98 (1.34-6.62 ) 0.007 3.28 (1.38-7.78 ) 0.007 3.74 (1.47-9.49 ) 0.005
TNFα 2.79 (1.38-5.63 ) 0.004 2.55 (1.27-5.14 ) 0.008 2.72 (1.30-5.71 ) 0.008
Anti-Idiotype events vs Crude results *** OR (IC, 95% ) p Model 1 * OR (IC, 95% ) p Model 2 ** OR (IC, 95% ) p
IL-1β 1.07 (1.02-1.12) 0.004 1.08 (1.02-1.13) 0.005 1.10 (1.03-1.17) 0.003
IL-6 1.02 (1.00-1.05) 0.03 1.02 (1.00-1.05) 0.04 1.02 (1.00-1.05) 0.02
IL-8 1.02 (0.98-1.06) 0.37 1.02 (0.98-1.06) 0.32 1.01 (0.97-1.06) 0.35
IL-10 1.02 (0.99-1.04) 0.20 1.01 (0.99-1.04) 0.26 1.01 (0.99-1.04) 0.15
IL-12p40 1.05 (1.01-1.10) 0.02 1.05 (1.00-1.10) 0.04 1.06 (1.01-1.11) 0.01
IL-17A 1.03 (0.99-1.07) 0.08 1.03 (0.99-1.06) 0.15 1.03 (1.00-1.08) 0.04
INF ϒ 1.09 (1.03-1.14) 0.002 1.08 (1.02-1.14) 0.004 1.10 (1.04-1.17) 0.001
Leptina 1.19 (0.98-1.45) 0.09 1.16 (0.95-1.40) 0.12 1.20 (0.97-1.49) 0.08
MIF 1.14 (1.01-1.29 ) 0.04 1.18 (1.02-1.36 ) 0.02 1.12 (0.98-1.28) 0.07
MCP-1 1.11 (1.03-1.20) 0.007 1.12 (1.03-1.21 ) 0.007 1.13 (1.03-1.23 ) 0.005
TNFα 1.10 (1.03-1.18) 0.004 1.09 (1.02-1.16) 0.008 1.10 (1.02-1.18) 0.008

*Model 1: Adjusted by age + Body mass index; **Model 2: Adjusted by Time since onset of disease + Time with biologic + complementary treatment with MTX; ***Adjusted to 10% increase of cytokine.


Conclusion: Patients with antidrug antibodies to IFX or ADA had higher ESR and DAS28 and a showed a significant association with higher levels of IFNg, MCP-1, MIF and TNFa.


REFERENCES:

[1]Parikh CR, Ponnampalam JK, Seligmann G, et al. Therapeutic Advances in Musculoskeletal Disease. 2021. doi:10.1177/1759720X211002685


Disclosure of Interests: Daniel Xavier Xibille Friedmann Speakers bureau: Lilly, Abbvie, Paid instructor for: Lilly, Abbvie, Consultant of: Lilly, Abbvie, Sandra Miriam Carrillo Vazquez Speakers bureau: Abbvie, Roche, Paid instructor for: Abbvie, Roche, Consultant of: Abbvie, Roche, Judith González Christen: None declared, David Vega Morales Speakers bureau: Abbvie, Roche, Paid instructor for: Abbvie, Roche, Consultant of: Abbvie, Roche, Mario Garza Elizondo Speakers bureau: Abbvie, Roche, Paid instructor for: Abbvie, Roche, Consultant of: Abbvie, Roche, Ramiro Hernández: None declared, José Eduardo Ortíz Panozo: None declared, José Luis Montiel Hernández: None declared

Citation: , volume 81, supplement 1, year 2022, page 391
Session: All you want to know about bDMARDs in RA. (Poster Tours)