THU0201 Older age, hypoalbuminaemia and renal failure might be poor prognosis factors for low dose methotrexate-induced myelosuppression in patients with rheumatoid arthritis
Authors: X-N Wei, D-H Zheng, Y-Q Mo, J-D Ma, Y-L Chen, L Dai
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Methotrexate (MTX) serves as an anchor drug in rheumatoid arthritis (RA) and the maximal dose of MTX from EULAR recommendation is 25–30 mg/w. Small cases retrospective cohort studies reported that the mortality rate of RA patients with low dose (5–25 mg/w) MTX-induced myelosuppression was about 17–25%. However, studies of low dose MTX-induced myelosuppression are rare in Chinese RA patients. <h3>Objectives</h3> To perform a retrospective case series analysis of the characteristics and outcomes of RA patients with low dose MTX-induced myelosuppression in China. <h3>Methods</h3> RA patients hospitalized at Sun Yat-Sen Memorial Hospital from January 2001 to December 2016 were recruited. Clinical data were collected and adverse effects were recorded simultaneously. Low dose MTX-induce myelosuppression was diagnosed as white blood cell &lt;4×10<sup>9</sup>/L together with hemoglobin &lt;130 g/L and platelet count &lt;130×10<sup>9</sup>/L after treatment of MTX without an alternative cause for pancytopenia. Data were showed as mean ± standard deviation. <h3>Results</h3> (1) There were 1137 RA patients recruited and 17 patients (1.5%) of them were hospitalized for low dose MTX-induce myelosuppression. Among these 17 patients, 53% were females, age was 68±5 years, disease duration was 12±11 years. (2) Four (23.5%) patients had dose errors, taking MTX 5–10mg daily for 24 days (range: 5–80), MTX accumulated dose was 25–200mg before myelosuppression. Mean MTX dose in the other patients (n=13, 76.5%) was 11.0±1.7 mg/w (range: 7.5 –15), course of MTX was 10±11 months (range: 0.5–48). Four (30.8%) patients manifested myelosuppression within the first month after taking MTX, and 4 (30.8%) patients had been well on a stable drug dose (7.5–12.5) for more than one year before myelosuppression, 2 patients manifested myelosuppression after adding MTX dose to 15mg/w for 2 months. (3) Fifteen (88.2%) patients had oral mucositis, eight of them had involvement of both oral mucosa and skin. Fever was noticed in 10 (58.8%) patients. Infections were recorded in 6 (35.3%) patients, manifested as pneumonia (n=4), sepsis (n=1), urinary tract infection (n=1) and skin soft tissue abscesses (n=1). Two patients experienced abdominal pain and melena. (4) Among the patients with neutropenia [n=17, mean neutrophil count: (0.74±0.76)×10<sup>9</sup>/L, range: 0–1.83], 9 (52.9%) developed severe neutropenia with neutrophil counts below 0.5×10<sup>9</sup>/L. Five patients developed severe thrombocytopenia (platelet count &lt;20×10<sup>9</sup>/L), and severe anemia occurred in 4 patients (hemoglobin &lt;65g/L). Hypoalbuminemia (30.0±2.8 g/L) was noted in all patients. Glomerular filtration rate (GFR)≤30 ml/min/1.73 m<sup>2</sup> was noted in 4 (23.5%) patients and GFR≤50 ml/min/1.73 m<sup>2</sup> in 12 (70.6%) patients. (5) Pancytopenia recovered (n=17) after discontinuation of MTX and supplementation of folic acid (10–30mg/d). Only 3 (17.6%) patients were treated with rescue intravenous leucovorin. Thirteen (76.5%) were treated with granulocyte colony stimulating factor (G-CSF) and 7 (41.2%) required blood products. Fifteen (88.2%) required antibiotic therapy. Sixteen (94.1%) patients was recovered and discharged, only one patient die from acute brainstem infarction but not from myelosuppression. <h3>Conclusions</h3> Older age, hypoalbuminaemia and renal failure might be poor prognosis factors for low dose MTX-induce myelosuppression in RA. <h3>Disclosure of Interest</h3> None declared