Dataset Information

Use of biologic agents and methotrexate improves renal manifestation and outcome in patients with rheumatoid arthritis: a retrospective analysis.

ABSTRACT:

Background and purpose

We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA).

Methods

We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990-1999 (n = 48); period 2, 2000-2009(n = 57); period 3, 2010-2019 (n = 51).

Results

Membranous nephropathy, nephrosclerosis, AA-amyloidosis, and IgA nephropathy were the four major renal manifestations of RA. AA-amyloidosis was diagnosed by kidney biopsy in 21 patients: period 1, 7 patients (15%); period 2, 10 patients (18%); and period 3, 4 patients (8%). The 4 patients in period 3 were in the years 2010-2014, and no new case of AA-amyloidosis was recorded from 2015 to 2019. In all 21 of the patients with AA-amyloidosis, neither a biologic agent nor methotrexate was administered. Fifteen of the 21 patients required dialysis, and 13 died in periods 1-3 because of amyloid-related cardiac dysfunction less than 2 years after the initiation of dialysis. Two of them are doing well using biologic agent despite dialysis. The remaining three patients who received a biologic agent or methotrexate does not progress to end-stage renal failure. In addition, the other renal complications showing progression to dialysis also decreased over time.

Conclusion

Advances in treatment strategies have improved renal outcome and reduced mortality in patients with RA.

SUBMITTER: Sawamura M

PROVIDER: S-EPMC8930889 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Use of biologic agents and methotrexate improves renal manifestation and outcome in patients with rheumatoid arthritis: a retrospective analysis.

Sawamura Masato M Sawa Naoki N Yamanouchi Masayuki M Ikuma Daisuke D Sekine Akinari A Mizuno Hiroki H Kawada Masahiro M Hiramatsu Rikako R Hayami Noriko N Hasegawa Eiko E Suwabe Tatsuya T Hoshino Junichi J Kono Kei K Kinowaki Keiichi K Ohashi Kenichi K Yamaguchi Yutaka Y Ubara Yoshifumi Y

Clinical and experimental nephrology 20211130 4

<h4>Background and purpose</h4>We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA).<h4>Methods</h4>We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990-1999 (n = 48); period ...[more]

PMID: 34846624

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Project description:BackgroundAccording to EULAR recommendations, biologic DMARDs (bDMARDs) such as tumor necrosis factor inhibitor, tocilizumab (TCZ), and abatacept (ABT) are in parallel when prescribing to rheumatoid arthritis (RA) patients who have shown insufficient response to conventional synthetic DMARDs. However, most prediction studies of therapeutic response to bDMARDs using gene expression profiles were focused on a single bDMARD, and consideration of the results from the perspective of RA pathophysiology was insufficient. The aim of this study was to identify the specific molecular biological features predicting the therapeutic outcomes of three bDMARDs (infliximab [IFX], TCZ, and ABT) by studying blood gene expression signatures of patients before biologic treatment in a unified test platform.MethodsRA patients who responded inadequately to methotrexate and were later commenced on any one of IFX (n = 140), TCZ (n = 38), or ABT (n = 31) as their first biologic between May 2007 and November 2011 were enrolled. Whole-blood gene expression data were obtained before biologic administration. Patients were categorized into remission (REM) and nonremission (NON-REM) groups according to CDAI at 6 months of biologic therapy. We employed Gene Set Enrichment Analysis (GSEA) to identify functional gene sets differentially expressed between these two groups for each biologic. Then, we compiled "signature scores" for these gene sets, and the prediction performances were assessed.ResultsGSEA showed that inflammasome genes were significantly upregulated with IFX in the NON-REM group compared with the REM group. With TCZ in the REM group, B-cell-specifically expressed genes were upregulated. RNA elongation, apoptosis-related, and NK-cell-specifically expressed genes were upregulated with ABT in the NON-REM group. Logistic regression analyses showed that "signature scores" of inflammasomes, B-cell-specifically expressed, and NK-cell-specifically expressed genes were significant, independently predictive factors for treatment outcome with IFX, TCZ, and ABT, respectively. The AUCs of ROC curves of these signature scores were 0.637, 0.796, and 0.768 for IFX, TCZ, and ABT, respectively.ConclusionsWe have identified original gene expression predictive signatures uniquely underlying the therapeutic effects of IFX, TCZ, and ABT. This is, to our knowledge, the first attempt to predict therapeutic effects of three drugs concomitantly using a unified gene expression test platform.

Dataset Information

Use of biologic agents and methotrexate improves renal manifestation and outcome in patients with rheumatoid arthritis: a retrospective analysis.

Background and purpose

Methods

Results

Conclusion

Publications

Use of biologic agents and methotrexate improves renal manifestation and outcome in patients with rheumatoid arthritis: a retrospective analysis.

Similar Datasets

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