Cause of death in patients with rheumatoid arthritis with particular reference to azathioprine.

Abstract

SUMMARY Three hundred and eleven patients with classical or definite rheumatoid arthritis were observed over an 11-year period. This group is of particular interest since 214 patients were given cytotoxic therapy, 203 were treated with azathioprine (52 of these also received chlorambucil or cyclophosphamide), and 11 were treated with cyclophosphamide or chlorambucil alone. Forty-six patients died. This is an excess mortality compared with the expected rate for the general population matched with respect to age and sex. The death rate was higher than expected in the age group 45-64 years but lower in those aged 75 years or over. There were more deaths from neoplasia and ischaemic heart disease in the younger age group. One patient died of lymphosarcoma; treatment had been with corticosteroids, gold, and chloroquine. No other tumours of the reticuloendothelial system were recorded, and no patient developed leukaemia.Several controlled studies have demonstrated suppression of disease activity in rheumatoid arthritis by azathioprine.'-' Since this treatment does not produce a lasting remission, long-term administration would be expected in many instances. This focuses attention on the adverse effects of prolonged administration of azathioprine, including bone marrow suppression, susceptibility to infection, and the potential development of malignant tumours.

On Inflammation and Cardiovascular Disease in Patients with Rheumatoid Arthritis

“…The study verified the increase of the overall death rate previously reported in several studies on patients with RA (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)44). In line with other reports, death was predicted by high age at disease onset and male sex (31,42,164) and cardiovascular event (165).…”

“…Generally, hospital-based materials (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) reveal standardized mortality ratios (SMR) in the range of 1.3-2.5 but figures as high as 3.0 have been reported (39)(40). In population-based studies the excess death rates are somewhat lower (SMR 1.16-1.37), but still significantly higher than in controls (41,42), except for in one study (43).…”

Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists

“…Likewise, entry into the cohorts in these studies was set to the date of the first discharge with RA, which may not necessarily equate to the date of diagnosis of RA. Although there are studies using other designs and follow up methods, [18][19][20][21][22][23] these have often been limited to a few hundred patients diagnosed and/or followed up before the 1990s.…”

Primäres ZNS-Lymphom während der Behandlung von Autoimmunerkrankungen mit Azathioprin

“…In Zusammenhang mit Azathioprin konzentrieren sich die Hinweise vor allem auf Lymphome, die sich vorzugsweise im ZNS manifestieren [21,25,27]. Während sich unter der durch Azathioprin bedingten Immunsuppression nach Organtransplantationen gehäuft PZNSL entwickeln [29], ist wenig über den kausalen Zusammenhang zwischen Azathioprin und PZNSL in der Behandlung von Autoimmunerkrankungen bekannt.…”

“…Die Kasuistik über ein PZNSL unter der Behandlung einer Autoimmunerkrankung mit Azathioprin bestätigt die bekannten Kasuistiken und ergibt einen weiteren Hinweise darauf, dass Thiopurine das Risiko von Malignomen, insbesondere von zerebralen Lymphomen, erhöhen [21,25,27].…”