Risk Factors Associated With Non-Respondence to Methotrexate in Rheumatoid Arthritis Patients

Siddiqui, Aman; Totonchian, Ali; Ali, Jamila Begum Jabar; Ahmad, Ishtiaq; Kumar, Jai; Shiwlani, Sheena; Haroon, Daniya Muhammad; Makheja, Neeraj; Rizwan, Amber

doi:10.7759/cureus.18112

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…On the contrary, we speculate if higher plasma levels of glucose could negatively affect response to DMARD treatment. In support of this hypothesis, previous studies have reported that presence of type 2 diabetes in patients with RA is associated with insufficient response to MTX (47). The metabolic syndrome has also been associated with a lower probability of achieving minimal disease activity in patients with PsA in therapy with TNFi (48).…”

Section: Discussionmentioning

confidence: 71%

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial

Kragsnaes,

Miguens Blanco,

Mullish

et al. 2023

ACR Open Rheumatology

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ObjectiveWe investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate‐treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).MethodsThis exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate‐to‐high peripheral PsA disease activity, despite at least 3 months of methotrexate‐treatment, were included in a 26‐week, double‐blind, 1:1 randomized, sham‐controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose‐to‐mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1H Nuclear Magnetic Resonance.ResultsTrial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017‐0.33]) vs. 0.012 [0‐0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N‐acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02).ConclusionIntestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.

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Section: Discussionmentioning

confidence: 71%

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial

Kragsnaes,

Miguens Blanco,

Mullish

et al. 2023

ACR Open Rheumatology

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“…Gender, BMI, smoke status, RF-positive status, and age at onset all affect the response of RA patients to MTX treatment, leading to different levels of treatment response and disease activity. 45 , 46 This may also explain the heterogeneous results that occurred when explored SNP genotypes and MTX disease response. The small number of participants in our study makes the results have some limitations.…”

Section: Discussionmentioning

confidence: 99%

MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis

Zhang¹,

Fu²,

Cao³

et al. 2023

PGPM

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Purpose Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms. Patients and Methods In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy. Results The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups. Conclusion Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.

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Rheumatoid arthritis study of the Egyptian College of Rheumatology (ECR): nationwide presentation and worldwide stance

et al. 2023

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To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%, p = 0.001). The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.

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Risk Factors Associated With Non-Respondence to Methotrexate in Rheumatoid Arthritis Patients

Cited by 3 publications

References 14 publications

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial

MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis

Rheumatoid arthritis study of the Egyptian College of Rheumatology (ECR): nationwide presentation and worldwide stance

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