REVIEW Meta‐analysis of neutrophil‐to‐lymphocyte and platelet‐to‐ lymphocyte ratio in rheumatoid arthritis Gian Luca Erre 1 | Panagiotis Paliogiannis 2 | Floriana Castagna 1 | Arduino Aleksander Mangoni 3 | Ciriaco Carru 2 | Giuseppe Passiu 1 | Angelo Zinellu 2 1 UOC Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Azienda Ospedaliero-Universitaria di Sassari e Università di Sassari, Sassari, Italy 2 Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy 3 Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, South Australia, Australia Correspondence Gian Luca Erre, UOC Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Azienda Ospedaliero- Universitaria di Sassari e Università di Sassari, Sassari, Italy. Email: e.gianluca@libero.it Abstract Background: We conducted a meta‐analysis to review the available evidence regarding the associations between peripheral blood neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) and the presence of rheuma- toid arthritis (RA). Methods: PubMed, Web of Science and Scopus, from inception to January 2018, were searched for studies reporting on NLR and PLR in RA in comparison with healthy subjects. Standardized mean difference (SMD) was calculated with a con- fidence interval (CI) of 95%. Results: Thirteen NLR studies (1550 RA patients and 1128 healthy controls) and 8 PLR studies (380 RA patients and 305 healthy controls) were included in the meta‐analysis. NLR and PLR were significantly higher in patients with RA when compared to controls (SMD = 0.79, 95% CI 0.55‐1.03; P < 0.001 and SMD = 0.66, 95% CI 0.43‐0.88; P < 0.001, respectively). Conclusions: The NLR and PLR are significantly associated with the presence of RA. Further studies are required to ascertain the potential clinical use of these simple and relatively inexpensive markers in RA diagnosis. KEYWORDS biomarkers, meta-analysis, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, rheumatoid arthritis, systematic review 1 | INTRODUCTION Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with systemic inflammation that affects mainly synovial joints leading to tissues destruction, disability and excess of mortality. 1 The prevalence rate for RA in Western countries is approximately 0.5%‐1% of the adult population. 2 Although the cause is still unknown, RA is thought to be the result of immune‐mediated mechanisms triggered by envi- ronmental factors in subjects harbouring a genetically favourable substrate. 1,2 Autoimmune response to post‐trans- lationally modified self‐proteins (eg, citrullinated‐peptides), innate and adaptive immune cells activation and production of pro‐inflammatory cytokines (TNF‐α, IL‐1, and IL‐6) are the pathophysiological hallmarks of the disease. 1,2 Complexity of RA pathogenesis is also mirrored by heterogeneous clinical presentation; as a result, despite recent improvement in early recognition, diagnosing RA remains a challenging and highly individualized process. 3 Among available serological parameters, autoantibody (rheumatoid factor, RF, and anti‐cyclic citrullinated peptide antibodies, ACPA) positivity and C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as markers of the inflammatory response status, are of paramount impor- tance in the diagnosis of RA. The most recent 2010 ACR/ EULAR classification criteria 4 (which include acute‐phase Received: 21 February 2018 | Revised: 2 October 2018 | Accepted: 10 October 2018 DOI: 10.1111/eci.13037 Eur J Clin Invest. 2019;49:e13037. https://doi.org/10.1111/eci.13037 wileyonlinelibrary.com/journal/eci © 2018 Stichting European Society for Clinical Investigation Journal Foundation | 1 of 11