Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis

Indhumathi, S; Rajappa, Medha; Chandrashekar, Laxmisha; Ananthanarayanan, Palghat Hariharan; Thappa, Devinder Mohan; Negi, Vir Singh

doi:10.1007/s00228-017-2255-x

Cited by 32 publications

(36 citation statements)

References 31 publications

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“…Similar to the results of both our study and the CHAMPION study, a recent case–control study in 126 Indian patients found age at onset, PASI scores, disease duration and presence of psoriatic arthritis not to be associated with clinical response to methotrexate . Univariate analysis in this study found BMI of more than 25 kg/m 2 and abdominal obesity to be significantly associated with the non‐responder group.…”

Section: Discussioncontrasting

confidence: 74%

Effectiveness of and factors associated with clinical response to methotrexate under daily life conditions in Asian patients with psoriasis: A retrospective cohort study

Pongparit

Chularojanamontri

Limphoka

et al. 2018

The Journal of Dermatology

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Given the relative scarcity of data concerning the efficacy of methotrexate under daily life conditions in psoriasis, this study aimed to investigate the effectiveness of methotrexate in Asian psoriatic patients and to identify factors associated with clinical response. This observational retrospective cohort study included adult psoriatic patients who had been treated with or were going to start methotrexate. Psoriasis Area and Severity Index (PASI) scores at baseline and at 3, 6 and 12 months were recorded. At 3 months, patients achieving 50% or more reduction from baseline PASI score were defined as responders. One hundred, 74 and 61 patients were followed for 3, 6 and 12 months, respectively. Mean follow-up time was 15.3 ± 10.2 months. A reduction in PASI score of at least 75% was achieved in 26%, 32.5% and 45.2% at 3, 6 and 12 months, respectively. At 12 and 24 months, Kaplan-Meier analysis showed 68.7% and 52.1% probability of drug survival, respectively. Male sex, body mass index (BMI) of less than 25 kg/m and absence of abdominal obesity were factors associated with response to treatment in univariate analysis. Male sex was the only significant factor in multivariate analysis. The effectiveness of methotrexate in clinical practise seemed to be lower than in clinical trials, but effectiveness increased with longer duration of treatment. Problems associated with methotrexate use in clinical practise may be due to medication adherence rather than lack of medication effectiveness. Female sex, abdominal obesity and BMI of 25 kg/m or more might decrease response to methotrexate.

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Section: Discussioncontrasting

confidence: 74%

Effectiveness of and factors associated with clinical response to methotrexate under daily life conditions in Asian patients with psoriasis: A retrospective cohort study

Pongparit

Chularojanamontri

Limphoka

et al. 2018

The Journal of Dermatology

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“…HLA‐Cw6 status was not correlated with clinical response to MTX, although the rates of PASI 75 response were higher in patients who were positive for HLA‐Cw6 at week 8 (33% vs. 15%) and week 12 (54% vs. 38%) compared with those who were negative for HLA‐Cw6. However, Indhumathi et al . showed that HLA‐Cw6 status acts as an independent genetic predictor of clinical responses to MTX in a South Indian Tamil population.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with TC/TT genotype of rs4112788 in LCE3D had a significantly higher frequency of PASI 90 response than those with CC genotype during the verification stage. Indhumathi et al . reported that LCE3B/3C deletion predisposes patients to clinical responses to MTX ( P = 0·03, OR 2·02).…”

Section: Discussionmentioning

confidence: 99%

TT genotype of rs10036748 in TNIP 1 shows better response to methotrexate in a Chinese population: a prospective cohort study

et al. 2019

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Summary Background Methotrexate (MTX) is an efficacious treatment for psoriasis; however, its widespread application is limited by its unpredictable efficacy. Objectives To investigate the association of clinical factors and variants of psoriasis susceptibility genes with clinical responses to MTX in a prospective cohort. Methods A total of 221 patients with psoriasis were recruited. Patients who achieved Psoriasis Area and Severity Index (PASI) improvement ≥ 75% at week 12 were defined as responders, whereas those with PASI improvement < 50% were defined as nonresponders. In 90 screening patients, genetic variants for 18 single‐nucleotide polymorphisms in 14 susceptibility genes, and HLA‐Cw6 status were initially compared for responders and nonresponders. Statistically significant associations in genetic variants were verified in all 221 patients. Results Overall, 49% and 45% of patients achieved PASI 75 improvement during screening and verification stages, respectively. Concomitant arthritis with psoriasis and high body mass index (BMI) negatively affect the efficacy of MTX. TT genotype of rs10036748 in TNIP1 was significantly associated with PASI 75 response at week 12 (54% and 37%, P < 0·05). A significantly higher PASI 90 response was observed in patients with TT genotype of rs10036748 (27% vs. 12%, P < 0·01) and TC/TT genotype of rs4112788 in LCE3D (25% vs. 13%, P < 0·05) at week 12 compared with those who had other genotypes. After adjustment for all confounding factors, only BMI (P < 0·05), arthritis (P < 0·05) and genotype of rs10036748 (P < 0·05) were significantly associated with clinical responses to MTX. Conclusions Patients with psoriasis with TT genotype of rs10036748 in TNIP1, with lower BMI, without arthritis will achieve a better response to MTX.

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“…In contrast to pharmacogenetic studies for RA patients, MTHFR C677T (rs1801133), MTHFR A1298C, ATIC C347G, RFC G80A and ADA G22A alleles or genotypes were not associated with a response to MTX in psoriasis patients . Recently, HLA‐Cw6 and FOXP3 (rs3761548) polymorphisms have been introduced as predictors of MTX response in the South Indian Tamil population . It also showed that the homozygotic presence of the minor T allele of MTHFR C677T (rs1801133) is associated with liver toxicity in patients with psoriatic arthritis under MTX therapy .…”

Section: Current Knowledge About Pharmacogenetics Of Adsmentioning

confidence: 99%

“…170 Recently, HLA-Cw6 and FOXP3 (rs3761548) polymorphisms have been introduced as predictors of MTX response in the South Indian Tamil population. 171 It also showed that the homozygotic presence of the minor T allele of MTHFR C677T (rs1801133) is associated with liver toxicity in patients with psoriatic arthritis under MTX therapy. 168 An association has been reported between the SNPs in ABCC1 (rs11075291, rs1967120, rs3784862, rs246240, rs3784864 and rs2238476), SLC19A1 (rs1051266) and ADORA2a (rs5760410) and MTX toxicity.…”

Section: Methotrexatementioning

confidence: 99%

Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases

2018

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For many years, a considerable number of patients with autoimmune diseases (ADs) have suffered from a lack of drug response and drug-related toxicity. Despite the emergence of new therapeutic options such as biological agents, patients continue to struggle with these problems. Unfortunately, new challenges, including the paradoxical effects of biological drugs, have complicated the situation. In recent decades, efforts have been made to predict drug response as well as drug-related side effects. Thanks to the many advances in genetics, evaluation of markers to predict drug response/toxicity before the initiation of treatment may be an avenue toward personalizing treatments. Implementing pharmacogenetics and pharmacogenomics in the clinic could improve clinical care; however, obstacles remain to effective personalized medicine for ADs. The present study attempted to clarify the concept of pharmacogenetics/pharmacogenomics for ADs. After an overview on the pathogenesis of the most common types of treatments, this paper focuses on pharmacogenetic studies related to the selected ADs. Bridging the gap between pharmacogenetics and personalized medicine is also discussed. Moreover, the advantages, disadvantages and recommendations related to making personalized medicine practical for ADs have been addressed.

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Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis

Cited by 32 publications

References 31 publications

Effectiveness of and factors associated with clinical response to methotrexate under daily life conditions in Asian patients with psoriasis: A retrospective cohort study

Effectiveness of and factors associated with clinical response to methotrexate under daily life conditions in Asian patients with psoriasis: A retrospective cohort study

TT genotype of rs10036748 in TNIP 1 shows better response to methotrexate in a Chinese population: a prospective cohort study

Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases

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