Tumour necrosis factor (TNF)α −308 G/G promoter polymorphism and TNFα levels correlate with a better response to adalimumab in patients with rheumatoid arthritis

Cuchacovich, Miguel; Soto, Lilian; Edwardes, Michael; Gutiérrez, Miguel; Llanos, Carolina; Pacheco, Daniel; Sabugo, Francisca; Alamo, M; Fuentealba, C; Villanueva, Luis; Gatica, H; Schiattino, Irene; Salazaro, L; Catalán, Diego; Valenzuela, Omar; Salazar‐Onfray, Flavio; Jc, Aguillón

doi:10.1080/03009740600904284

Cited by 73 publications

(46 citation statements)

References 17 publications

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“…We contacted the authors of these two studies, who reconfirmed their data. Nevertheless, analysis of the four remaining studies (8,13,15,16) showed no significant heterogeneity (I 2 ¼ 0%), and the overall difference in DAS28 score decreased, but remained significantly different from zero (difference ¼ 0.53, 95% CI: 0.18, 0.88, P ¼ 0.0033). Five of the six studies, which reported DAS28 score also used this as the criterion to determine responsiveness to the TNF-a inhibitor.…”

Section: Tnf-a à308 G/a Variant and Anti-tnf-a Agents D D O'rielly Et Almentioning

confidence: 99%

“…7 At present, there are a handful of small studies that have set out to examine whether the G to A polymorphism at position À308 in the promoter of the TNFa gene influences clinical response to TNF blockade in patients with moderate-to-severe RA. [8][9][10][11][12][13][14][15][16] Owing to the relatively small number of patients exposed to anti-TNF-a agents in all of the pharmacogenetic studies in RA to date, each individual study had insufficient power to conclusively determine if the À308 variant of the TNF-a gene would be helpful in predicting patients that respond poorly to TNF-a blockade. Lee et al 17 carried out a metaanalysis investigating the association of TNF-a À308 G/A polymorphism with responsiveness to TNF-a-blockers in RA.…”

Section: Introductionmentioning

confidence: 99%

“…17 However, in the 3 years since that report, there have been an additional four studies investigating the association of TNF-a À308 G/A polymorphism with responsiveness to TNF-a-blockers in RA. [13][14][15][16] These recent studies account for an additional 408 RA patients exposed to anti-TNF-a agents, including 306 responders and 102 non-responders. As a result, we set out to carry out a more current and detailed meta-analysis of the effect of TNF-a À308 A/G variant and response to anti-TNF-a therapy in patients with RA.…”

Section: Introductionmentioning

confidence: 99%

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TNF-α −308 G/A polymorphism and responsiveness to TNF-α blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis

et al. 2009

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Although tumor necrosis factor-a (TNF-a) blockade is a very effective therapy for rheumatoid arthritis (RA), not all patients achieve a favorable outcome. The objective of this study was to determine if the common TNF-a variant À308(A) predicts poor response to TNF-a inhibitors in RA patients using meta-analysis. Studies were identified using MEDLINE and EMBASE. Data were extracted based on DAS28 or achieving at least American College of Rheumatology 20 response. A total of nine studies met the inclusion criteria representing a total of 692 RA patients. There was no significant heterogeneity among study effect sizes (P ¼ 0.36). The frequency of the A allele was 22% (119/531) in responders and 37% (60/161) in nonresponders. The odds of having the A allele was lower in responders versus non-responders (odds ratio (OR) ¼ 0.43, 95% confidence intervals (CI): 0.28À0.68, P ¼ 0.000245), irrespective of the TNF-a inhibitor prescribed, indicating that the À308(A) variant predicts poor response to TNF-a inhibitors. The clinical utility of prospectively genotyping for this variant when initiating anti-TNF-a therapy for RA should now be formally assessed.

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Section: Tnf-a à308 G/a Variant and Anti-tnf-a Agents D D O'rielly Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TNF-α −308 G/A polymorphism and responsiveness to TNF-α blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis

et al. 2009

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“…However, Marotte et al [16] reported controversial results that TNF-α -308 SNP was not associated with response to infliximab therapy in RA patients. In another report, TNFα -308 GG promoter polymorphism had better response to adalimumab therapy than GA phenotype in 81 active RA patients [18].…”

Section: Discussionmentioning

confidence: 99%

Influence of promoter region of TNF-α gene polymorphisms on anti-TNF treatment in rheumatoid arthritis: Preliminary report

Turgay¹,

Aydeniz²,

Pehlıvan³

et al. 2017

Pau Med J

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Purpose:The aim of this study was to explore the association between promotor polymorphisms in tumor necrosis factor α (TNF-α) gene and disease activity,clinical parameters and response to different treatments in rheumatoid arthritis patients. Materials and methods:We analyzed single nucleotide polymorphisms (-308,-238 and -857) in TNF-α gene in 65 patients with active RA who were treated with DMARD or anti-TNF therapy and in 70 control ones who had no rheumatologic problems.TNF-α genotyping were performed by the PCR-RFLP method.Clinical responses were compared by using disease activity score,VAS and health assessment questionnaire at baseline and after 6 months of treatment. Results:A significant positive association was observed at TNF-857 CC genotype in RA patients (p=0.046). At the six months the mean VAS,HAQ and DAS 28 improvement was not significant among groups.Improvement in DAS score was significantly better in -308 GG genotype than -308 AG genotype in anti-TNF subgroup. Conclusion:Our results suggest that TNF-857 CC genotype may be associated with susceptibility to disease and polymorphism in TNF-308 genotype may have an effect in response to therapy.Further studies should be warranted to establish TNF-α polymorphisms and susceptibility and response to treatment inrheumatoid arthritis patients.Pam Med J 2017; 10 (3):216-220 Keywords:Rheumatoid arthritis,TNF-α, gene,promoter polymorphisms. ÖzetAmaç:Bu çalışmanın amacı romatoid artrit hastalarında tümör nekrozis alfa geni (TNF-α) promotor polimorfizmi ile hastalık aktivitesi,klinik parametreler ve değişik tedavilere yanıt arasında ilişkiyi belirlemektir. Gereç ve yöntem:Çalışmamızda DMARD veya anti-TNF tedavisi alan 65 aktif romatoid artrit hastası ve 70 romatolojik hastalığı olmayan kontrol grubunda -308,-238,-857 içeren TNF-α'nın tek nukleotid polimorfizmi PCR-RFLP yöntemi kullanılarak analiz edildi.Tedaviye klinik yanıt hastalık aktivite skoru,görsel analog ölçek ve sağlık değerlendirme anketi kullanılarak başlangıçta ve 6 aylık tedavi sonrasında değerlendirildi. Bulgular:Romatoid artrit hastalarında TNF-857 CC genotipinin anlamlı olarak fazla olduğu saptandı.Altı aylık tedavi sonunda grupların VAS;HAQ ve hastalık aktivite skorlarında iyileşme benzer bulundu.Buna rağmen hastalık aktivite skorlarında iyileşme TNF grubundaki hastalarda -308 GG genotipi olanlarda -308 AG genotipi olanlara göre daha iyiydi. Sonuç:Romatoid artrit hastalarında TNF-857 CC genotipinin hastalığı yatkınlık sağlayabileceği;Aynı zamanda -308 genotinideki polimorfizmin tedaviye yanıtta bir rolü olabilir.Romatoid artrit hastalarında TNF-α polimorfizmi ve hastalığa yatkınlık ve tedaviye yanıtın belirlenmesinde ileri çalışmalara gereksinim vardır. Tıp Derg 2017; 10 (3):216-220 Pam

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“…As an example, one study has shown that patients bearing the GGC haplotype of TNF gene (-238G/-308G/-857C) in a homozygous form showed low response rate to ADA treatment (26), whereas in another study, TNF -308 homozygous (G/G) patients showed better response than heterozygous (G/A) patients (27). In other studies the development of antibodies directed against adalimumab has been shown to be associated with interleukin-(IL)10 polymorphisms (28).…”

Section: Discussionmentioning

confidence: 99%

NOD2, CD14 and TLR4 mutations do not influence response to adalimumab in patients with Crohn's disease: a preliminary report

Acosta

Ouburg

Morré

et al. 2010

Rev. esp. enferm. dig.

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Tumour necrosis factor (TNF)α −308 G/G promoter polymorphism and TNFα levels correlate with a better response to adalimumab in patients with rheumatoid arthritis

Abstract: A relationship between DAS28 improvement, the -308 G/G polymorphism, and increased circulating TNFalpha levels was found in Chilean RA patients treated with adalimumab.

Cited by 73 publications

References 17 publications

TNF-α −308 G/A polymorphism and responsiveness to TNF-α blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis

TNF-α −308 G/A polymorphism and responsiveness to TNF-α blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis

Influence of promoter region of TNF-α gene polymorphisms on anti-TNF treatment in rheumatoid arthritis: Preliminary report

NOD2, CD14 and TLR4 mutations do not influence response to adalimumab in patients with Crohn's disease: a preliminary report

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