Shaye Kivity1, Yaron Zafrir2, Ronen Loebstein3, Rachel Pauzner4, Meir Mouallem4, Haim Mayan4. 1. Department of Medicine A, The Chaim Sheba Medical Center, Ramat-Gan, Israel; Dr. Pinchas Borenstein Talpiot Medical Leadership Program 2013, The Chaim Sheba Medical Center, Ramat-Gan, Israel; Zabludovicz Center for Autoimmune Diseases, The Chaim Sheba Medical Center, Ramat-Gan, Israel; Sackler School of Medicine, Ramat-Aviv, Israel. Electronic address: kivitys@gmail.com. 2. Zabludovicz Center for Autoimmune Diseases, The Chaim Sheba Medical Center, Ramat-Gan, Israel. 3. Institute of Clinical Pharmacology & Toxicology, The Chaim Sheba Medical Center, Ramat-Gan, Israel; Sackler School of Medicine, Ramat-Aviv, Israel. 4. Department of Medicine E, The Chaim Sheba Medical Center, Ramat-Gan, Israel; Sackler School of Medicine, Ramat-Aviv, Israel.
Abstract
OBJECTIVE: Low dose (10-25 mg/week) methotrexate is widely used for the management of systemic inflammatory diseases, and is considered to be relatively safe. Toxicity due to low dose MTX has been reported but is poorly characterized. We describe the clinical features, risk factors, and outcomes of low dose MTX toxicity in a large case series at our center. PATIENTS AND METHODS: We conducted a retrospective case series of all adult (>18 years) patients hospitalized at Sheba Medical Center, between 2005 and 2012 for low dose MTX toxicity. RESULTS: We identified 28 patients (age: 70.4±13.7 years, range: 33-88; 20 (71%) females) hospitalized for low dose MTX toxicity. Indications for MTX therapy included: rheumatoid arthritis (39.2%), psoriasis±arthritis (21.5%), polymyalgia rheumatica (10.8%) and other inflammatory conditions (28.5%). Pancytopenia was the most common manifestation of low dose MTX toxicity detected in 78.5% of the patients. Potential risk factors included acute renal failure, hypoalbuminemia, concurrent use of drugs known to interact with MTX, and dose errors. Serum MTX concentrations (n=20, mean 0.04±0.07 μg/mL range: 0-0.3) did not correlate with the degree of either neutropenia (r=-0.36; p=0.18) or thrombocytopenia (r=0.44; p=0.10). Seven (25%) patients died, all from pancytopenia followed by sepsis. Serum MTX concentrations did not differ between the patients who died from MTX toxicity (n=6; mean: 0.05±0.04 μg/mL) and those who survived the toxicity (n=14 mean 0.04±0.08; p=0.45). CONCLUSIONS: Low-dose MTX toxicity can be life threatening, mainly due to myelosuppression. There is no rationale for MTX therapeutic drug monitoring in the setting of low-dose toxicity.
OBJECTIVE: Low dose (10-25 mg/week) methotrexate is widely used for the management of systemic inflammatory diseases, and is considered to be relatively safe. Toxicity due to low dose MTX has been reported but is poorly characterized. We describe the clinical features, risk factors, and outcomes of low dose MTXtoxicity in a large case series at our center. PATIENTS AND METHODS: We conducted a retrospective case series of all adult (>18 years) patients hospitalized at Sheba Medical Center, between 2005 and 2012 for low dose MTXtoxicity. RESULTS: We identified 28 patients (age: 70.4±13.7 years, range: 33-88; 20 (71%) females) hospitalized for low dose MTXtoxicity. Indications for MTX therapy included: rheumatoid arthritis (39.2%), psoriasis±arthritis (21.5%), polymyalgia rheumatica (10.8%) and other inflammatory conditions (28.5%). Pancytopenia was the most common manifestation of low dose MTXtoxicity detected in 78.5% of the patients. Potential risk factors included acute renal failure, hypoalbuminemia, concurrent use of drugs known to interact with MTX, and dose errors. Serum MTX concentrations (n=20, mean 0.04±0.07 μg/mL range: 0-0.3) did not correlate with the degree of either neutropenia (r=-0.36; p=0.18) or thrombocytopenia (r=0.44; p=0.10). Seven (25%) patients died, all from pancytopenia followed by sepsis. Serum MTX concentrations did not differ between the patients who died from MTXtoxicity (n=6; mean: 0.05±0.04 μg/mL) and those who survived the toxicity (n=14 mean 0.04±0.08; p=0.45). CONCLUSIONS: Low-dose MTXtoxicity can be life threatening, mainly due to myelosuppression. There is no rationale for MTX therapeutic drug monitoring in the setting of low-dose toxicity.
Authors: Jeffrey A Sparks; Medha Barbhaiya; Elizabeth W Karlson; Susan Y Ritter; Soumya Raychaudhuri; Cassandra C Corrigan; Fengxin Lu; Jacob Selhub; Daniel I Chasman; Nina P Paynter; Paul M Ridker; Daniel H Solomon Journal: Semin Arthritis Rheum Date: 2017-02-10 Impact factor: 5.532