Muthu S, Jeyaraman M, Ranjan R, Jha SK. Remission is not maintained over 2 years with hematopoietic stem cell transplantation for rheumatoid arthritis: A systematic review with meta-analysis. World J Biol Chem 2021; 12(6): 114-130 [PMID: 34904049 DOI: 10.4331/wjbc.v12.i6.114]
Corresponding Author of This Article
Sathish Muthu, MS, Research Scholar, School of Engineering and Technology, Sharda University, Greater Noida, Delhi 201306, Uttar Pradesh, India. drsathishmuthu@gmail.com
Research Domain of This Article
Rheumatology
Article-Type of This Article
Meta-Analysis
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Sathish Muthu, Madhan Jeyaraman, Saurabh Kumar Jha, Department of Biotechnology, School of Engineering and Technology, Sharda University, Delhi 201306, Uttar Pradesh, India
Sathish Muthu, Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624001, Tamil Nadu, India
Madhan Jeyaraman, Department of Orthopaedics, Faculty of Medicine, Sri Lalithambigai Medical College and Hospital, Chennai 600095, Tamil Nadu, India
Rajni Ranjan, Department of Orthopaedics, School of Medical Sciences and Research, Greater Noida 201306, Uttar Pradesh, India
Author contributions: Muthu S and Jeyaraman M provide the conceptualization; Muthu S, Jeyaraman M, and Ranjan R contributed to the data curation, formal analysis, investigations, methodology; Muthu S and Ranjan R contributed to the administration, resources, and supervision; Muthu S contributed to the validation and visualization; Muthu S and Jeyaraman M contributed to writing the original draft and reviewing the drafts.
Conflict-of-interest statement: The authors declare no conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sathish Muthu, MS, Research Scholar, School of Engineering and Technology, Sharda University, Greater Noida, Delhi 201306, Uttar Pradesh, India. drsathishmuthu@gmail.com
Received: March 30, 2021 Peer-review started: March 30, 2021 First decision: May 12, 2021 Revised: May 21, 2021 Accepted: November 26, 2021 Article in press: November 26, 2021 Published online: November 27, 2021
Abstract
BACKGROUND
Hematopoietic stem cell (HSC) transplantation (HSCT) is being accepted as a standard of care in various inflammatory diseases. The treatment of rheumatoid arthritis (RA) has been closely evolving with the understanding of disease pathogenesis. With the rising resistance to the traditional disease-modifying anti-rheumatic drugs and targeted biological therapy, researchers are in pursuit of other methods for disease management. Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance, HSCT attracts much attention considering its reparative, paracrine, and anti-inflammatory effects. However, a systematic review of studies on HSCT in RA is lacking.
AIM
To investigate the role of HSCT in the management of RA.
METHODS
A detailed search of PubMed, Scopus, EMBASE, Cochrane, and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines. We extracted data including the number of patients, source of hematopoietic stem cells, their mobilization and conditioning regimens, results, and complications from the eligible studies. Results were dichotomized into success (ACR 50/70) and failure (ACR 20) based on the improvement from baseline characteristics. The methodological quality of the included studies was also assessed. Analysis was performed using OpenMeta[Analysis] software.
RESULTS
We included 17 studies (1 randomized controlled trial, 11 prospective, and 5 retrospective studies) with 233 patients for analysis. HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria (Z = 11.309, P < 0.001). However, the remission was noted only till 24 mo and later on the significance of the result was lost (Z = 1.737, P = 0.082). A less than 1% treatment-related mortality was noted from the included studies. No major drug-related toxicities were noted in any of the included studies. All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections. It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous (Z = 9.972, P < 0.001) and allogenic (Z = 6.978, P < 0.001) sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them (I2 = 99.4, P < 0.001).
CONCLUSION
Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years, the inclusion of HSCT into the standard of care of RA needs further exploration.
Core Tip: With the rising resistance to the traditional disease-modifying anti-rheumatic drugs and targeted biological therapy, we performed this systematic review and meta-analysis to evaluate the role of hematopoietic stem cell therapy in the management of rheumatoid arthritis. Literature on the effectiveness of the intervention is encouraging with significant improvement till 2 years post-therapy. We have explored the ambiguity in the current treatment methods in hematopoietic stem cell therapy that needs further exploration to optimize the results out of this treatment modality.
