Back to Journals » Pragmatic and Observational Research » Volume 10

Casual effect of methotrexate+etanercept/infliximab on survival of patients with rheumatoid arthritis

Authors Akhlaghi S, Sahebari M, Mahmoodi M, Yaseri M, Mansournia MA, Zeraati H

Received 15 November 2018

Accepted for publication 23 January 2019

Published 18 April 2019 Volume 2019:10 Pages 23—28

DOI https://doi.org/10.2147/POR.S194408

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Professor David B Price


Saeed Akhlaghi,1 Maryam Sahebari,2 Mahmoud Mahmoodi,1 Mehdi Yaseri,1 Mohammad Ali Mansournia,1 Hojjat Zeraati1

1Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 2Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, Iran

Background and objectives: Following the discovery of new drugs, physicians and pharmaceutical companies have become interested in examining patients’ mortality and morbidity rates. In this respect, the effects of methotrexate (MTX)+etanercept/infliximab (ETA/INF) therapy on the survival of rheumatoid arthritis patients (RA) were evaluated in this study using marginal structural piecewise constant baseline hazard model.
Patients and methods: According to the standard protocol, MTX is considered as the first-line treatment for RA patients. If there is no adequate response to MTX, biologic drugs will be added. To compare the survival rates of RA patients in MTX- and MTX+ETA/INF-treated groups, the piecewise constant baseline hazard model was fitted. Then, due to the existence of the time-dependent confounder (VAS) which was affected by previous treatment, the weight for each person-time was calculated via the inverse probability treatment weighting method. These weights were then used by marginal structural piecewise constant baseline hazard model. Finally, these models were compared.
Results: The median (IQR) of the follow-up period in patients receiving MTX+ETN/INF and MTX was 11 (15.25) and 11 (31), respectively, and the 8-year survival rate was reported by 70% versus 68%, respectively. First, the piece-wise constant baseline hazard model was fitted. Fitting the given model showed that MTX+ETA/INF had a significant effect on patients’ survival (HR=0.789, 95% CI [0.634, 0.983]). Second, marginal structural piecewise constant baseline hazard model was fitted. But, the results of this model revealed that MTX+ETA/INF did not have a significant impact on patients’ survival (HR=0.968, 95% CI [0.860, 1.090]).
Conclusion: Adjusting the pain score over time as a time-dependent confounder via marginal structural piecewise constant baseline hazard model, it has been demonstrated that MTX+ETA/INF does not have a significant effect on patients’ survival rates. Therefore, a significant difference can be found between survival rates of these groups using longitudinal studies.

Keywords: survival, biologics, IPTW, propensity score, time-dependent confounder, marginal structural models, piece-wise constant baseline hazard model


Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]