BACKGROUND AND DESIGN: Methotrexate (MTX) hepatotoxicity in psoriatic patients is well recognized, but there are discrepancies in the reported incidence and associated risk factors. This retrospective study describes 104 Nova Scotian patients with psoriasis seen between 1979 and 1990. Patients received MTX over one to 11 years (mean 3.38), with baseline and annual follow-up liver biopsies. Clinical data were obtained by chart review. Statistical analysis evaluated the risks associated with obesity, diabetes, alcohol consumption and duration of therapy, with the histological grade of liver biopsies. RESULTS: Of the 104 patients, 35 were obese, 10 were diabetic and 37 occasionally consumed alcohol. At the end of the study, 21 patients had developed severe hepatic fibrosis (grade IIIB), and three developed liver cirrhosis (grade IV). Significant risk of severe hepatotoxicity is related to diabetes (P = 0.02) but not to obesity (P = 0.12) or alcohol consumption (P = 0.12). All patients with cirrhosis took MTX for two years in standard doses of 20 to 25 mg/week. CONCLUSIONS: In this first Canadian study evaluating MTX hepatotoxicity in psoriatics, the incidence of severe hepatotoxicity is high: 23.1% (24 of 104 patients). This study shows that diabetic patients are particularly at increased risk of MTX hepatotoxicity. Occasional alcohol consumption is not associated with increased risk. Three patients who developed cirrhosis over two years of standard MTX therapy may represent a subset of psoriatics with increased hepatic susceptibility to MTX. Another three patients whose severe hepatic fibrosis had regressed upon discontinuation of MTX, but who developed accelerated recurrence of the severe hepatic fibrosis upon resumption of MTX therapy, also suggest the possibility of unusual sensitivity to the drug. These cases emphasize the need for continuing surveillance, with regular liver biopsies, of psoriatic patients on MTX.
BACKGROUND AND DESIGN:Methotrexate (MTX) hepatotoxicity in psoriaticpatients is well recognized, but there are discrepancies in the reported incidence and associated risk factors. This retrospective study describes 104 Nova Scotian patients with psoriasis seen between 1979 and 1990. Patients received MTX over one to 11 years (mean 3.38), with baseline and annual follow-up liver biopsies. Clinical data were obtained by chart review. Statistical analysis evaluated the risks associated with obesity, diabetes, alcohol consumption and duration of therapy, with the histological grade of liver biopsies. RESULTS: Of the 104 patients, 35 were obese, 10 were diabetic and 37 occasionally consumed alcohol. At the end of the study, 21 patients had developed severe hepatic fibrosis (grade IIIB), and three developed liver cirrhosis (grade IV). Significant risk of severe hepatotoxicity is related to diabetes (P = 0.02) but not to obesity (P = 0.12) or alcohol consumption (P = 0.12). All patients with cirrhosis took MTX for two years in standard doses of 20 to 25 mg/week. CONCLUSIONS: In this first Canadian study evaluating MTXhepatotoxicity in psoriatics, the incidence of severe hepatotoxicity is high: 23.1% (24 of 104 patients). This study shows that diabeticpatients are particularly at increased risk of MTXhepatotoxicity. Occasional alcohol consumption is not associated with increased risk. Three patients who developed cirrhosis over two years of standard MTX therapy may represent a subset of psoriatics with increased hepatic susceptibility to MTX. Another three patients whose severe hepatic fibrosis had regressed upon discontinuation of MTX, but who developed accelerated recurrence of the severe hepatic fibrosis upon resumption of MTX therapy, also suggest the possibility of unusual sensitivity to the drug. These cases emphasize the need for continuing surveillance, with regular liver biopsies, of psoriaticpatients on MTX.
Authors: Lydia Tchambaz; Chantal Schlatter; Max Jakob; Anita Krähenbühl; Peter Wolf; Stephan Krähenbühl Journal: Drug Saf Date: 2006 Impact factor: 5.606
Authors: Rachel A Elliott; Koen D Putman; Matthew Franklin; Lieven Annemans; Nick Verhaeghe; Martin Eden; Jasdeep Hayre; Sarah Rodgers; Aziz Sheikh; Anthony J Avery Journal: Pharmacoeconomics Date: 2014-06 Impact factor: 4.981
Authors: Jasvinder A Singh; Gordon Guyatt; Alexis Ogdie; Dafna D Gladman; Chad Deal; Atul Deodhar; Maureen Dubreuil; Jonathan Dunham; M Elaine Husni; Sarah Kenny; Jennifer Kwan-Morley; Janice Lin; Paula Marchetta; Philip J Mease; Joseph F Merola; Julie Miner; Christopher T Ritchlin; Bernadette Siaton; Benjamin J Smith; Abby S Van Voorhees; Anna Helena Jonsson; Amit Aakash Shah; Nancy Sullivan; Marat Turgunbaev; Laura C Coates; Alice Gottlieb; Marina Magrey; W Benjamin Nowell; Ana-Maria Orbai; Soumya M Reddy; Jose U Scher; Evan Siegel; Michael Siegel; Jessica A Walsh; Amy S Turner; James Reston Journal: Arthritis Rheumatol Date: 2018-11-30 Impact factor: 10.995
Authors: Jasvinder A Singh; Gordon Guyatt; Alexis Ogdie; Dafna D Gladman; Chad Deal; Atul Deodhar; Maureen Dubreuil; Jonathan Dunham; M Elaine Husni; Sarah Kenny; Jennifer Kwan-Morley; Janice Lin; Paula Marchetta; Philip J Mease; Joseph F Merola; Julie Miner; Christopher T Ritchlin; Bernadette Siaton; Benjamin J Smith; Abby S Van Voorhees; Anna Helena Jonsson; Amit Aakash Shah; Nancy Sullivan; Marat Turgunbaev; Laura C Coates; Alice Gottlieb; Marina Magrey; W Benjamin Nowell; Ana-Maria Orbai; Soumya M Reddy; Jose U Scher; Evan Siegel; Michael Siegel; Jessica A Walsh; Amy S Turner; James Reston Journal: Arthritis Care Res (Hoboken) Date: 2018-11-30 Impact factor: 4.794