title: High Methotrexate Triglutamate Level Is an Independent Predictor of Adverse Effects in Asian Indian Rheumatoid Arthritis Patients-A Preliminary Study.
abstract: It is unclear whether erythrocyte methotrexate polyglutamate levels (MTX-glun) are associated with response or adverse effects to methotrexate in rheumatoid arthritis. This preliminary study evaluated their utility in Asian Indian patients over 24 weeks.
  
  
  
  Rheumatoid arthritis patients were started on oral methotrexate at a dose of 15 mg/wk, which was escalated to 25 mg by 12 weeks and continued till 24 weeks. Erythrocyte (RBC) MTX-glu1 to MTX-glu5 levels (nmol/L RBC) were determined at 4, 8, 16, and 24 weeks by using reverse-phase high-performance liquid chromatography. Area under the concentration curve (AUC) of MTX-glu1-5, MTX-glu3-5, and MTX-glu3 levels was compared between groups with regards to response and adverse effects.
  
  
  
  This study included 117 patients with mean (SD) age of 42.7 (±11.9) years and disease duration of 2.0 (1.7) years. Mean (SD) RBC MTX-glu1-5 levels at 4, 8, 16, and 24 weeks were 93 (±29), 129 (±46), 143 (±49), and 159 (±65) nmol/L RBC; the highest individual polyglutamate was MTX-glu3 (40%). There was significant correlation between MTX-glu1-5 (r = 0.38, P < 0.001) and MTX-glu3 (r = 0.49, P < 0.001) with methotrexate dose. There was no significant difference of AUC MTX-glun between responders and nonresponders. However, AUC MTX-glu3 was significantly (P = 0.03) higher in patients with adverse effects. On logistic regression, AUC of MTX-glu3 [odds ratio = 1.004 (95% confidence interval 1.002-1.007)] and methotrexate dose at 24 weeks were independent predictors of adverse effects.
  
  
  
  In this preliminary study, higher levels of RBC MTX-glu3 were found to be the independent predictors for adverse effects in rheumatoid arthritis patients.
authors.affiliation: *Department of Internal Medicine (Rheumatology Unit), Postgraduate Institute of Medical Education and Research; †Department of Biochemistry, Punjab University; ‡Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research; §Department of Biochemistry, Government Medical College and Hospital; and ¶Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Sandhu
authors.forename: Varun
authors.initials: V
authors.lastname: Dhir
authors.forename: Archana
authors.initials: A
authors.lastname: Bhatnagar
authors.forename: Veena
authors.initials: V
authors.lastname: Dhawan
authors.forename: Jasbinder
authors.initials: J
authors.lastname: Kaur
authors.forename: Ankita
authors.initials: A
authors.lastname: Sood
authors.forename: Shankar
authors.initials: S
authors.lastname: Naidu
authors.forename: Shabeer
authors.initials: S
authors.lastname: Ahmad
authors.forename: Neelam
authors.initials: N
authors.lastname: Varma
authors.forename: Aman
authors.initials: A
authors.lastname: Sharma
authors.forename: Shefali
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018501:Antirheumatic Agents; D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate