Dataset Information

Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort.

ABSTRACT: The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.

SUBMITTER: Salvador-Martin S

PROVIDER: S-EPMC9861004 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort.

Salvador-Martín Sara S Zapata-Cobo Paula P Velasco Marta M Palomino Laura M LM Clemente Susana S Segarra Oscar O Sánchez Cesar C Tolín Mar M Moreno-Álvarez Ana A Fernández-Lorenzo Ana A Pérez-Moneo Begoña B Loverdos Inés I Navas López Victor Manuel VM Millán Antonio A Magallares Lorena L Torres-Peral Ricardo R García-Romero Ruth R Pujol-Muncunill Gemma G Merino-Bohorquez Vicente V Rodríguez Alejandro A Salcedo Enrique E López-Cauce Beatriz B Marín-Jiménez Ignacio I Menchén Luis L Laserna-Mendieta Emilio E Lucendo Alfredo J AJ Sanjurjo-Sáez María M López-Fernández Luis A LA

International journal of molecular sciences 20230116 2

The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Gen ...[more]

PMID: 36675312

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Project description:ObjectivesPatient activation is an important consideration for improved health outcomes in the management of chronic diseases. Limited English proficiency among patients and primary care providers has been shown to be a predictor for worse health across disease states. We aimed to determine the baseline patient activation measure (PAM) among Spanish-speaking (SP) and English-speaking (ES) pediatric patients with IBD and parents, and to describe the feasibility and efficacy of a novel peer-group education symposium designed to enhance patient activation as measured with the PAM.MethodsTwo separate half-day educational symposia in either Spanish or English were presented and moderated by 2 native SP physicians. Content for each of the presentations were highly standardized and interactive, designed to address each of the activation domains (self-management, collaboration with a health care provider, maintenance of function and prevention of disease exacerbation, and appropriate access to high-quality care). Descriptive statistics were used to describe changes between pre- and postsymposium PAM trends.ResultsEleven primarily SP and 21 ES families participated in their respective symposium. Paired pre- and post-PAM scores were available from 24 pediatric patients with IBD (8 SP, 16 ES) and 41 parents (15 SP, 26 ES). The mean age for SP and ES patients was 11.6 and 12.0 years, and female sex in 80% and 62%, respectively. Paired pre- and post-PAM scores for all participants (n = 65) were analyzed. PAM scores uniformly increased in all 4 groups after the symposia (SP patients 59.1-70.3, P = 0.05; SP parents 69.8-75.2, P = 0.2; ES patients 59.9-64.0, P = 0.08; ES parents 61.9-69.1, P = 0.002), although only the ES-parents group had sufficient sample size (n = 26) to achieve statistical significance. The overall cohort had an aggregate increase from pre-PAM of 62.9 (SD 14.5) to post-PAM of 69.4 (SD 13.9) (<0.001).ConclusionsWe describe a novel peer-group educational symposium presented in Spanish and English languages to increase patient and parent activation in pediatric patients with IBD and their caregiving parents. The use of PAM to assess levels of activation appears to be feasible and effective in these groups.

Project description:Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th-20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology.

Dataset Information

Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort.

Publications

Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort.

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