Background 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.
Objectives To perform a retrospective case series analysis of the characteristics and outcomes of RA patients with low dose MTX-induced myelosuppression in China.
Methods 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 <4×109/L together with hemoglobin <130 g/L and platelet count <130×109/L after treatment of MTX without an alternative cause for pancytopenia. Data were showed as mean ± standard deviation.
Results (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)×109/L, range: 0–1.83], 9 (52.9%) developed severe neutropenia with neutrophil counts below 0.5×109/L. Five patients developed severe thrombocytopenia (platelet count <20×109/L), and severe anemia occurred in 4 patients (hemoglobin <65g/L). Hypoalbuminemia (30.0±2.8 g/L) was noted in all patients. Glomerular filtration rate (GFR)≤30 ml/min/1.73 m2 was noted in 4 (23.5%) patients and GFR≤50 ml/min/1.73 m2 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.
Conclusions Older age, hypoalbuminaemia and renal failure might be poor prognosis factors for low dose MTX-induce myelosuppression in RA.
Disclosure of Interest None declared