Decision tree analysis for evaluating disease activity in patients with rheumatoid arthritis

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Abstract

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammatory synovitis. We developed a new disease activity evaluation system using important cytokines to help doctors better evaluate disease activity in patients with RA.

Methods

Flow cytometry was used to detect the levels of seven cytokines. Then, the results were analyzed using an R language decision tree.

Results

The levels of six cytokines, namely interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ, were significantly different between the active disease and remission stages. Decision tree analysis of the six cytokines with statistical significance identified two judgment rules for the remission stage and three judgment rules for the active disease stage.

Conclusion

We proposed the use of the decision tree method to analyze cytokine levels in patients with RA and obtain a more intuitive and objective RA disease activity scoring system. This method revealed the relationships of IL-6 and TNF-α levels with inflammatory characteristics in patients with RA, which can help predict disease activity.

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Most cited references 21

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The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.

Ferdinand C Breedveld, Michael Weisman, Arthur F Kavanaugh … (2006)

To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. This was a 2-year, multicenter, double-blind, active comparator-controlled study of 799 RA patients with active disease of < 3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score. Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P < or = 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups. In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.

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Cytokines in the pathogenesis of rheumatoid arthritis.

Georg Schett, Georg Schett (2007)

Cytokines regulate a broad range of inflammatory processes that are implicated in the pathogenesis of rheumatoid arthritis. In rheumatoid joints, it is well known that an imbalance between pro- and anti-inflammatory cytokine activities favours the induction of autoimmunity, chronic inflammation and thereby joint damage. However, it remains less clear how cytokines are organized within a hierarchical regulatory network, and therefore which cytokines may be the best targets for clinical intervention a priori. Here, we discuss the crucial effector function of cytokines in the immunological processes that are central to the pathogenesis of rheumatoid arthritis.

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Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score.

D van der Heijde, M van 't Hof, P. van Riel … (1990)

An investigation of clinical and laboratory variables which might form the basis for judging disease activity in clinical practice was made by six rheumatologists in a prospective study of up to three years' duration of 113 patients with early rheumatoid arthritis. Decisions to start treatment with slow acting antirheumatic drugs were equated with moments of high disease activity. If treatment with slow acting antirheumatic drugs was not started or if the slow acting antirheumatic drug remained unchanged for at least one year or if treatment was stopped because of disease remission, this was equated with periods of low disease activity. Two groups, one with high and one with low disease activity according to the above criteria, were formed. Factor analysis was performed to enable easy handling of the large number of clinical and laboratory variables without loss of information; this resulted in five factors. Next, discriminant analysis was done to determine to what extent each factor contributed to discrimination between the two groups of differing disease activity. Finally, a multiple regression analysis was carried out to determine which laboratory and clinical variables underlie the factors of the discriminant function, resulting in a 'disease activity score'. This score consisted of the following variables: Ritchie index, swollen joints, erythrocyte sedimentation rate, and general health, in declining importance. The rheumatologists' decisions to prescribe slow acting antirheumatic drugs, or not, were mainly based on articular symptoms.

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Author and article information

Journal

Journal ID (nlm-ta): J Int Med Res

Journal ID (iso-abbrev): J Int Med Res

Journal ID (publisher-id): IMR

Journal ID (hwp): spimr

Title: The Journal of International Medical Research

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Print): 0300-0605

ISSN (Electronic): 1473-2300

Publication date (Electronic): 20 October 2021

Publication date Collection: October 2021

Volume: 49

Issue: 10

Electronic Location Identifier: 03000605211053232

Affiliations

[1 ]Molecular Diagnosis Laboratory, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China

[2 ]Department of Rheumatology and Immunology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China

[3 ]Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, Hangzhou, China

Author notes

[*]Wanmao Ni and Lijuan Wang, Molecular Diagnosis Laboratory, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No.158 Shangtang road, Gongshu District, Hangzhou, Zhejiang 310000, China; Department of Rheumatology and Immunology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No.158 Shangtang road, Gongshu District, Hangzhou, Zhejiang 310000, China. Email: wm_ni@ 123456163.com ; wanglijuan9281@ 123456sina.com

Author information

Lei Wang https://orcid.org/0000-0003-0008-3224

Article

Publisher ID: 10.1177_03000605211053232

DOI: 10.1177/03000605211053232

PMC ID: 8543724

PubMed ID: 34670422

SO-VID: 0460edd9-be75-437f-aded-0e2a0bd6eec8

License:

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 2 March 2021

Date accepted : 22 September 2021

Funding

Funded by: Zhejiang Medical Technology Plan Project;

Award ID: WKJ-ZJ-1709

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Keywords: rheumatoid arthritis,cytokine,decision tree analysis,interleukin-6,tumor necrosis factor-α,disease activity,interferon-γ

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Keywords: rheumatoid arthritis, cytokine, decision tree analysis, interleukin-6, tumor necrosis factor-α, disease activity, interferon-γ

Decision tree analysis for evaluating disease activity in patients with rheumatoid arthritis

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Abstract

Objective

Methods

Results

Conclusion

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International Journal of Medicine and Medical Research

Most cited references 21

The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.

Cytokines in the pathogenesis of rheumatoid arthritis.

Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score.

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