Dataset Information

Early Prognostic Factors Associated with the Efficacy of Infliximab Treatment for Patients with Rheumatoid Arthritis with Inadequate Response to Methotrexate.

ABSTRACT:

Introduction

Early prognostic factors for the clinical response in patients with rheumatoid arthritis (RA) after 1 year of treatment with infliximab (IFX) as part of routine clinical practice were investigated.

Methods

Thirty-five patients with RA with an inadequate response to methotrexate were enrolled and administered IFX (3-9 mg/kg, every 4-8 weeks). Serum trough levels of IFX and levels of 9 cytokines were measured at baseline and at 3, 6 months, and 1 year. Associations between these parameters and clinical indicators were statistically analyzed.

Results

Serum trough levels of IFX and serum levels of interleukin (IL)-6 in the early phase of IFX treatment were investigated. Patients with low serum IL-6 achieved a higher clinical response as evaluated by the European League Against Rheumatism response criteria. Notably, the serum levels of IL-6 and IL-10 at baseline exhibited a significant positive correlation with disease activity at 1 year. Low serum levels of IL-6 and IL-10 at baseline were associated with low Disease Activity Score 28 erythrocyte sedimentation rate (DAS28-ESR). Cut-off values of IL-6 (5.45 pg/mL) and IL-10 and (1.68 pg/mL) enabled discrimination of DAS28-ESR remission from non-remission with high sensitivity and moderate specificity.

Conclusion

Following the initiation of IFX treatment, early disease activity and remission were associated with serum levels of IL-6. Serum levels of IL-6 and IL-10 at baseline predict the efficacy after 1 year of treatment with IFX. Patients with high serum levels of IL-6 and IL-10 at baseline before IFX treatment might require more intensive therapy to achieve higher rates of clinical remission at 1 year.

Funding

Eisai Co., Ltd.

SUBMITTER: Hayashi S

PROVIDER: S-EPMC4999572 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Early Prognostic Factors Associated with the Efficacy of Infliximab Treatment for Patients with Rheumatoid Arthritis with Inadequate Response to Methotrexate.

Hayashi Satoko S Suzuki Katsuya K Yoshimoto Keiko K Takeshita Masaru M Kurasawa Takahiko T Yamaoka Kunihiro K Takeuchi Tsutomu T

Rheumatology and therapy 20151211 1

<h4>Introduction</h4>Early prognostic factors for the clinical response in patients with rheumatoid arthritis (RA) after 1 year of treatment with infliximab (IFX) as part of routine clinical practice were investigated.<h4>Methods</h4>Thirty-five patients with RA with an inadequate response to methotrexate were enrolled and administered IFX (3-9 mg/kg, every 4-8 weeks). Serum trough levels of IFX and levels of 9 cytokines were measured at baseline and at 3, 6 months, and 1 year. Associations betw ...[more]

PMID: 27747509

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Project description:Methotrexate (MTX) is the standard first-line therapy in rheumatoid arthritis (RA) with variable clinical efficacy that is difficult to predict. The glycosylation status of immunoglobulin G (IgG) is altered in RA and influenced by MTX treatment. We aimed to further investigate if IgG glycosylation in untreated early RA can predict therapeutic response to MTX.We used a shotgun proteomic approach to screen for the Fc glycopeptides in the serum of 12 control subjects and 59 untreated patients with early RA prior to and following MTX initiation. MTX treatment response was defined according to the European League Against Rheumatism at a median of 14 weeks (range 13-15) after treatment initiation. Seropositive patients were defined as those testing positive for anticitrullinated protein antibodies and/or rheumatoid factor at baseline (n = 44). Data analysis was performed using uni- and multivariate statistics.We could confirm a low abundance of galactosylated glycans in untreated patients with early RA compared with control subjects that was partially restored by MTX treatment. This was more evident among future nonresponders than among responders to MTX treatment. Results were further validated and confirmed by multivariate statistical analysis of the baseline Fc glycan, proteomic, and clinical data. We found that the ratio between the main agalactosylated (FA2) and main mono- and di-galactosylated Fc glycans (FA2G1 and FA2G2) of IgG1 ranked as the most prominent factor distinguishing responders from nonresponders. A low baseline ratio of FA2/[FA2G1 + FA2G2]-IgG1 was associated with nonresponse (OR 5.3 [1.6-17.0]) and was able to discriminate future nonresponders from responders to MTX therapy with a sensitivity of 70% (95% CI 46-88%) and a specificity of 69% (95% CI 52-83%). For seropositive patients (n = 44), this trend was improved with a sensitivity of 73% (95% CI 45-92%) for nonresponse and a specificity of 79% (95% CI 60-92%).We show that the FA2/[FA2G1 + FA2G2] of IgG1 is a biomarker candidate that is significantly associated with nonresponding patients and has potential value for prediction of MTX clinical response.

Project description:This study aimed to identify baseline metabolic biomarkers for response to methotrexate (MTX) therapy in rheumatoid arthritis (RA) using an untargeted method. In total, 82 baseline plasma samples (41 insufficient responders and 41 sufficient responders to MTX) were selected from the Treatment in the Rotterdam Early Arthritis Cohort (tREACH, trial number: ISRCTN26791028) based on patients' EULAR response at 3 months. Metabolites were assessed using high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Differences in metabolite concentrations between insufficient and sufficient responders were assessed using partial least square regression discriminant analysis (PLS-DA) and Welch's t-test. The predictive performance of the most significant findings was assessed in a receiver operating characteristic plot with area under the curve (AUC), sensitivity and specificity. Finally, overrepresentation analysis was performed to assess if the best discriminating metabolites were enriched in specific metabolic events. Baseline concentrations of homocystine, taurine, adenosine triphosphate, guanosine diphosphate and uric acid were significantly lower in plasma of insufficient responders versus sufficient responders, while glycolytic intermediates 1,3-/2,3-diphosphoglyceric acid, glycerol-3-phosphate and phosphoenolpyruvate were significantly higher in insufficient responders. Homocystine, glycerol-3-phosphate and 1,3-/2,3-diphosphoglyceric acid were independent predictors and together showed a high AUC of 0.81 (95% CI: 0.72-0.91) for the prediction of insufficient response, with corresponding sensitivity of 0.78 and specificity of 0.76. The Warburg effect, glycolysis and amino acid metabolism were identified as underlying metabolic events playing a role in clinical response to MTX in early RA. New metabolites and potential underlying metabolic events correlating with MTX response in early RA were identified, which warrant validation in external cohorts.

Dataset Information

Early Prognostic Factors Associated with the Efficacy of Infliximab Treatment for Patients with Rheumatoid Arthritis with Inadequate Response to Methotrexate.

Introduction

Methods

Results

Conclusion

Funding

Publications

Early Prognostic Factors Associated with the Efficacy of Infliximab Treatment for Patients with Rheumatoid Arthritis with Inadequate Response to Methotrexate.

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