Studio del possibile ruolo predittivo del polimorfismo -174G>C del promotore dell'IL-6 nei confronti della risposta al rituximab in corso di artrite reumatoide

Translated title of the contribution: Study on the possible role of the -174G>C IL-6 promoter polymorphism in predicting response to rituximabin rheumatoid arthritis

M. Fabris, L. Quartuccio, S. Lombardi, M. Benucci, M. Manfredi, M. Saracco, F. Atzeni, P. Morassi, M. A. Cimmino, E. Pontarini, C. Fabro, R. Pellerito, P. Sarzi-Puttini, M. Cutolo, A. Carletto, L. M. Bambara, F. Fischetti, F. Curcio, E. Tonutti, S. de Vita

Research output: Contribution to journalArticle

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Abstract

Objective. Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. The -174G>C interleukin-6 (IL-6) promoter polymorphism was investigated in RA patients treated with rituximab (RTX), being IL-6 a key cytokine for B cell survival and proliferation, thus possibly implicated in rituximab efficacy. Methods. The study was conducted in a real-life retrospective cohort of 142 unselected RA patients (120F/22M) treated with RTX and referred to 7 rheumatologic centres in the north of Italy. One hundred and thirteen (79.6%) patients were rheumatoid factor (RF)-positive and 112 (78.9%) were anti-CCP antibodies positive. The response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR criteria (DAS28) and the ACR criteria. The IL-6 -174G>C promoter polymorphism was analyzed by RFLP following previously reported methods. Results. Lack of response to RTX at month +6 by EULAR criteria was more prevalent in RA patients with the IL-6 - 174 CC genotypes (9/21, 42.8%), than in the GC/GG patients (23/121, 19.0%) (OR 3.196, 95% CI=1.204-8.485; p=0.0234). Similar results were found when evaluating the response by ACR criteria. No differences were found in RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status according to the different IL-6 -174 genotypes. Conclusion. IL-6 promoter genotyping may be useful to better plan treatment with RTX in RA. Larger replication studies are in course to confirm these preliminary results.

Original languageItalian
Pages (from-to)253-258
Number of pages6
JournalReumatismo
Volume62
Issue number4
Publication statusPublished - 2010

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Interleukin-6
Rheumatoid Arthritis
Rheumatoid Factor
ametantrone
Genotype
Biological Products
Restriction Fragment Length Polymorphisms
Italy
Rituximab
Anti-Idiotypic Antibodies
Cell Survival
B-Lymphocytes
Biomarkers
Cell Proliferation
Cytokines
Therapeutics

ASJC Scopus subject areas

  • Rheumatology

Cite this

Fabris, M., Quartuccio, L., Lombardi, S., Benucci, M., Manfredi, M., Saracco, M., ... de Vita, S. (2010). Studio del possibile ruolo predittivo del polimorfismo -174G>C del promotore dell'IL-6 nei confronti della risposta al rituximab in corso di artrite reumatoide. Reumatismo, 62(4), 253-258.

Studio del possibile ruolo predittivo del polimorfismo -174G>C del promotore dell'IL-6 nei confronti della risposta al rituximab in corso di artrite reumatoide. / Fabris, M.; Quartuccio, L.; Lombardi, S.; Benucci, M.; Manfredi, M.; Saracco, M.; Atzeni, F.; Morassi, P.; Cimmino, M. A.; Pontarini, E.; Fabro, C.; Pellerito, R.; Sarzi-Puttini, P.; Cutolo, M.; Carletto, A.; Bambara, L. M.; Fischetti, F.; Curcio, F.; Tonutti, E.; de Vita, S.

In: Reumatismo, Vol. 62, No. 4, 2010, p. 253-258.

Research output: Contribution to journalArticle

Fabris, M, Quartuccio, L, Lombardi, S, Benucci, M, Manfredi, M, Saracco, M, Atzeni, F, Morassi, P, Cimmino, MA, Pontarini, E, Fabro, C, Pellerito, R, Sarzi-Puttini, P, Cutolo, M, Carletto, A, Bambara, LM, Fischetti, F, Curcio, F, Tonutti, E & de Vita, S 2010, 'Studio del possibile ruolo predittivo del polimorfismo -174G>C del promotore dell'IL-6 nei confronti della risposta al rituximab in corso di artrite reumatoide', Reumatismo, vol. 62, no. 4, pp. 253-258.
Fabris, M. ; Quartuccio, L. ; Lombardi, S. ; Benucci, M. ; Manfredi, M. ; Saracco, M. ; Atzeni, F. ; Morassi, P. ; Cimmino, M. A. ; Pontarini, E. ; Fabro, C. ; Pellerito, R. ; Sarzi-Puttini, P. ; Cutolo, M. ; Carletto, A. ; Bambara, L. M. ; Fischetti, F. ; Curcio, F. ; Tonutti, E. ; de Vita, S. / Studio del possibile ruolo predittivo del polimorfismo -174G>C del promotore dell'IL-6 nei confronti della risposta al rituximab in corso di artrite reumatoide. In: Reumatismo. 2010 ; Vol. 62, No. 4. pp. 253-258.
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title = "Studio del possibile ruolo predittivo del polimorfismo -174G>C del promotore dell'IL-6 nei confronti della risposta al rituximab in corso di artrite reumatoide",
abstract = "Objective. Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. The -174G>C interleukin-6 (IL-6) promoter polymorphism was investigated in RA patients treated with rituximab (RTX), being IL-6 a key cytokine for B cell survival and proliferation, thus possibly implicated in rituximab efficacy. Methods. The study was conducted in a real-life retrospective cohort of 142 unselected RA patients (120F/22M) treated with RTX and referred to 7 rheumatologic centres in the north of Italy. One hundred and thirteen (79.6{\%}) patients were rheumatoid factor (RF)-positive and 112 (78.9{\%}) were anti-CCP antibodies positive. The response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR criteria (DAS28) and the ACR criteria. The IL-6 -174G>C promoter polymorphism was analyzed by RFLP following previously reported methods. Results. Lack of response to RTX at month +6 by EULAR criteria was more prevalent in RA patients with the IL-6 - 174 CC genotypes (9/21, 42.8{\%}), than in the GC/GG patients (23/121, 19.0{\%}) (OR 3.196, 95{\%} CI=1.204-8.485; p=0.0234). Similar results were found when evaluating the response by ACR criteria. No differences were found in RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status according to the different IL-6 -174 genotypes. Conclusion. IL-6 promoter genotyping may be useful to better plan treatment with RTX in RA. Larger replication studies are in course to confirm these preliminary results.",
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author = "M. Fabris and L. Quartuccio and S. Lombardi and M. Benucci and M. Manfredi and M. Saracco and F. Atzeni and P. Morassi and Cimmino, {M. A.} and E. Pontarini and C. Fabro and R. Pellerito and P. Sarzi-Puttini and M. Cutolo and A. Carletto and Bambara, {L. M.} and F. Fischetti and F. Curcio and E. Tonutti and {de Vita}, S.",
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T1 - Studio del possibile ruolo predittivo del polimorfismo -174G>C del promotore dell'IL-6 nei confronti della risposta al rituximab in corso di artrite reumatoide

AU - Fabris, M.

AU - Quartuccio, L.

AU - Lombardi, S.

AU - Benucci, M.

AU - Manfredi, M.

AU - Saracco, M.

AU - Atzeni, F.

AU - Morassi, P.

AU - Cimmino, M. A.

AU - Pontarini, E.

AU - Fabro, C.

AU - Pellerito, R.

AU - Sarzi-Puttini, P.

AU - Cutolo, M.

AU - Carletto, A.

AU - Bambara, L. M.

AU - Fischetti, F.

AU - Curcio, F.

AU - Tonutti, E.

AU - de Vita, S.

PY - 2010

Y1 - 2010

N2 - Objective. Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. The -174G>C interleukin-6 (IL-6) promoter polymorphism was investigated in RA patients treated with rituximab (RTX), being IL-6 a key cytokine for B cell survival and proliferation, thus possibly implicated in rituximab efficacy. Methods. The study was conducted in a real-life retrospective cohort of 142 unselected RA patients (120F/22M) treated with RTX and referred to 7 rheumatologic centres in the north of Italy. One hundred and thirteen (79.6%) patients were rheumatoid factor (RF)-positive and 112 (78.9%) were anti-CCP antibodies positive. The response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR criteria (DAS28) and the ACR criteria. The IL-6 -174G>C promoter polymorphism was analyzed by RFLP following previously reported methods. Results. Lack of response to RTX at month +6 by EULAR criteria was more prevalent in RA patients with the IL-6 - 174 CC genotypes (9/21, 42.8%), than in the GC/GG patients (23/121, 19.0%) (OR 3.196, 95% CI=1.204-8.485; p=0.0234). Similar results were found when evaluating the response by ACR criteria. No differences were found in RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status according to the different IL-6 -174 genotypes. Conclusion. IL-6 promoter genotyping may be useful to better plan treatment with RTX in RA. Larger replication studies are in course to confirm these preliminary results.

AB - Objective. Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. The -174G>C interleukin-6 (IL-6) promoter polymorphism was investigated in RA patients treated with rituximab (RTX), being IL-6 a key cytokine for B cell survival and proliferation, thus possibly implicated in rituximab efficacy. Methods. The study was conducted in a real-life retrospective cohort of 142 unselected RA patients (120F/22M) treated with RTX and referred to 7 rheumatologic centres in the north of Italy. One hundred and thirteen (79.6%) patients were rheumatoid factor (RF)-positive and 112 (78.9%) were anti-CCP antibodies positive. The response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR criteria (DAS28) and the ACR criteria. The IL-6 -174G>C promoter polymorphism was analyzed by RFLP following previously reported methods. Results. Lack of response to RTX at month +6 by EULAR criteria was more prevalent in RA patients with the IL-6 - 174 CC genotypes (9/21, 42.8%), than in the GC/GG patients (23/121, 19.0%) (OR 3.196, 95% CI=1.204-8.485; p=0.0234). Similar results were found when evaluating the response by ACR criteria. No differences were found in RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status according to the different IL-6 -174 genotypes. Conclusion. IL-6 promoter genotyping may be useful to better plan treatment with RTX in RA. Larger replication studies are in course to confirm these preliminary results.

KW - IL-6

KW - Pharmacogenetics

KW - Rheumatoid arthritis

KW - Rituximab

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