AB0654 NEUTROPHIL-TO-LYMPHOCYTE RATIO, LEUKOCYTIC FORMULA REVERSAL AND PREVALENCE OF LARGE GRANULAR T LYMPHOCYTE LEUKEMIA IN AN ITALIAN MONOCENTRIC RHEUMATOID ARTHRITIS COHORT
Authors: DI Taranto, A. Amati, G. Cincinelli, L. Giudice, M. Biggioggero, M. Manara, F. Ingegnoli, E. G. Favalli, R. F. Caporali
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The neutrophil-to-lymphocyte ratio (NLR) is a universally recognized as sensitive marker of inflammation, even in Rheumatoid Arthritis (RA). It has been shown to correlate with C-reactive protein levels thus proving to be an additional diagnostic tool and marker of disease activity. A preliminary study found that NLR values &lt;2 at baseline result in a greater likelihood of achieving clinical remission. Anecdotal reports and longitudinal studies have associated TNF inhibitors (TNFi) use with the development of lymphocytosis or neutropenia, and a subsequent reduction of NLR. Large Granular Lymphocyte T-leukemia (LGL-T) is a chronic, indolent lymphoproliferative disorder seldom described in association with autoimmune diseases, including RA. <h3>Objectives:</h3> To evaluate NLR and the prevalence of leukocytic formula (N/L) reversal in a large cohort of RA patients on biologic or targeted synthetic DMARDs (b/tsDMARDs) and to investigate possible correlations with disease activity, response to treatment and development of complications, like LGL-T leukemia. <h3>Methods:</h3> Adult RA patients treated with b/tsDMARDs were consecutively enrolled in this single-center study. Demographic, clinical and clinimetric data were collected for each patient, along with laboratory records. Specifically, we collected data regarding the absolute number of leukocytes, neutrophils and lymphocytes, collecting the prevalence of leukocyte formula alterations such as neutropenia (N&lt;1500/ml), lymphocytosis (L&gt;3000/ml), absolute lymphocytosis (L&gt;5000/ml) and N/L reversal. <h3>Results:</h3> 506 patients on b/tsDMARD therapy have been consecutively enrolled (47.6% on TNFi, 17.4% on JAK inhibitors (JAKi), 5.9% on anti-CD20, 52.2% on csDMARD, and 35% on corticosteroids). 46.8% of patients were in remission according to SDAI, 6.3% had neutropenia, 19.2% lymphocytosis, 1.2% absolute lymphocytosis, and 26.7% N/L reversal. Demographic, clinical, clinimetric and laboratory differences for patients with or without N/L reversal are shown in Table 1. No differences have been found for sex, age, age of RA onset, disease duration, BMI, clinical presentation, comorbidity, and median SDAI. The 135 patients (26.7%) with N/L inversion had significantly higher rates of N&lt;1500 (p&lt;0.001), L&gt;3000 (p&lt;0.001), and L&gt;5000 (p&lt;0.001). The median NLR of these patients is 0.789, compared to 1.63 of patients with preserved formula. Regarding disease characteristics, the only difference is in the percentage of multi-drug resistant (MDR, &gt;2 failed Mechanisms of Action) patients, lower in the N/L reversal subgroup (10.4% vs 18.3%, p=0.03). Regarding treatment, the use of TNFi is associated with N/L reversal respect to non-TNFi (63% vs 42%, p&lt;0.001), whereas the use of JAKi and anti-CD20, as expected, is associated with preserved formula (20.8% vs 8.1%, p&lt;0.001 and 7.3% vs 2.2%, p=0.03, respectively). Considering the population with moderate or high disease activity (Table 2) according to SDAI (SDAI&gt;11: 65 patients, 12.8%), a high percentage of preserved formula is found (81.75% vs 18.25%, p&lt;0.001). Among the latter, no patients had neutropenia or lymphocytosis, which were found in 5 and 2 patients with inverted N/L, respectively. In this subgroup no association was found between N/L reversal and MoAs. In our cohort, four patients (0.008%) presented LGL-T: 3 of them were on etanercept at the time of diagnosis, one showed mild neutropenia and absolute lymphocytosis, one severe neutropenia and one with lymphocytosis. <h3>Conclusion:</h3> Alterations of leukocytic formula are not uncommon in patients with RA, occurring in our cohort in 26.7% of cases, especially on TNFi therapy. Our results confirm that the NLR may be an additional marker of disease activity and worse response to b/tsDMARD treatment (MDR-RA). The use of TNFi is associated with higher rates of N/L reversal in patients in remission or low disease activity, whereas it does not seem to mask increases in NLR in moderate or high activity conditions. More pronounced alterations in leukocyte counts may also mask hematologic complications such as LGL-T leukemia, underscoring a yet unknown potential relationship between leukemia pathology, RA and its therapies. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Raffaele Di Taranto: None declared, Andrea Amati: None declared, Gilberto Cincinelli: None declared, Laura Giudice: None declared, Martina Biggioggero Galapagos, Maria Manara Novartis, Angelini, UCB Pharma, Eli Lilly, MSD, Francesca Ingegnoli: None declared, Ennio Giulio Favalli AbbVie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, and UCB Pharma, AbbVie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, and UCB Pharma, Roberto F. Caporali AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma.