Adverse effects of low dose methotrexate in rheumatoid arthritis patients.
OBJECTIVE
To determine the frequency of adverse effects attributed to Methotrexate (MTX) toxicity and serum minimum toxic concentration with low dose MTX in Rheumatoid Arthritis (RA) patients.


METHODS
Cross-sectional observational study.


METHODS
Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from March 2010 to March 2011.


METHODS
One hundred and forty adult patients of RA receiving low dose MTX (10 mg/week) for at least 3 months, ere included by consecutive sampling. Blood samples were collected 2 hours after the oral dose of MTX. Serum alanine transaminase and creatinine were analyzed on Hitachi and blood counts on Sysmex analyzer. Serum MTX concentration was measured on TDX analyzer.


RESULTS
Out of one hundred and forty patients; 68 males (49%) and 72 females (51%), 38 developed MTX toxicity (27%), comprising of hepatotoxicity in 12 (8.6%), nephrotoxicity in 3 (2.1%), anaemia in 8 (5.7%), leucopenia in 2 (1.4%), thrombocytopenia in 3 (2.1%), pancytopenia in 2 (1.4%), gastrointestinal adverse effects in 5 (3.6%) and mucocutaneous problems in 3 (2.1%). Receiver operating characteristic curve revealed serum minimum toxic concentration of MTX at cutoff value of 0.71 μmol/l with a sensitivity of 71% and specificity of 76%.


CONCLUSIONS
Adverse effects of low dose MTX were found in 27% of RA patients, mainly comprising of hepatotoxicity and haematological problems. MTX toxicity can be detected by therapeutic drug monitoring of serum concentration of 0.71 μmol/l with sensitivity of 71% and specificity of 76% in the patients on low dose MTX maintenance therapy.
Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan.
Syed Tanveer Abbas
ST
Gilani
Dilshad Ahmed
DA
Khan
Farooq Ahmad
FA
Khan
Mushtaq
M
Ahmed
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000453:epidemiology; D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007970:Leukopenia / Q000139:chemically induced / Q000453:epidemiology; D008099:Liver / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D008875:Middle Aged; D010198:Pancytopenia / Q000139:chemically induced / Q000453:epidemiology; D011379:Prognosis; D012372:ROC Curve; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology; D055815:Young Adult
D018501:Antirheumatic Agents; D008727:Methotrexate