Toxicity profiles of disease modifying antirheumatic drugs in rheumatoid arthritis.
The toxicity profiles of 7 disease modifying antirheumatic drugs (DMARD) (hydroxychloroquine, intramuscular (im) gold, D-penicillamine, oral gold, methotrexate (MTX), azathioprine and cyclophosphamide) were evaluated in 2,479 patients with rheumatoid arthritis consecutively enrolled at 5 centers in the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) program. Incidence rates for side effects are reported as events/1000 patient-years. Our descriptive study revealed an individual profile of prevalent toxicities for each drug. Oral gold was characterized by substantial lower gastrointestinal (GI) toxicity (diarrhea 391 events/1000 patient-years, loose bowel movement 148, lower abdominal pain 76), MTX by hepatotoxicity (47) while D-penicillamine had the only clinically significant incidence of altered taste (40). MTX users reported the most mucosal ulcers (87), followed by oral gold (76), im gold (55) and D-penicillamine (38). Rash was frequently seen with gold compounds and D-penicillamine, while upper GI toxicity was common with immunosuppressive agents. Cyclophosphamide had 48% discontinuations within 6 months. MTX had the lowest discontinuation rate in the first 6 months, but then showed little difference from im gold. A preliminary similarity index was developed to compare the toxicity profiles of various DMARD. Close similarities were found between toxicity profiles of im gold and D-penicillamine, and between azathioprine and MTX. Oral gold had a unique toxicity pattern. Knowledge of these different toxicity patterns can enable more appropriate selection of agents for particular patients.
Department of Medicine, Stanford University School of Medicine, CA.
G
G
Singh
J F
JF
Fries
C A
CA
Williams
E
E
Zatarain
P
P
Spitz
D A
DA
Bloch
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006046:Gold / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010396:Penicillamine / Q000009:adverse effects / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D006886:Hydroxychloroquine; D006046:Gold; D003520:Cyclophosphamide; D010396:Penicillamine; D001379:Azathioprine; D008727:Methotrexate