RISK OF CANCER FROM AZATHIOPRINE THERAPY IN MULTIPLE-SCLEROSIS - A CASE-CONTROL STUDY

An increased risk of cancer has been reported in patients treated with azathioprine. To assess the long-term risk of neoplasia in azathiopri ne-treated multiple sclerosis (MS) patients, we conducted a case-contr ol study using the Lyon Multiple Sclerosis Database. From the 1,191 MS patients included in the database, we identified patients who develop ed cancer before December 31, 1991. Each case was then matched to thre e cancer-free MS controls by gender, date of birth, and date of MS ons et. A matched analysis was performed to compare cases and controls for exposure to azathioprine therapy during the same follow-up period. Tw enty-three MS patients with cancer were identified: 17 solid tumors, 2 skin carcinomas, 4 hematopoietic cancers. Cases had a mean age of 34. 5 years +/- 10.2 (+/-SD) at clinical onset of MS and have been followe d up for an average 13.8 years +/- 8.1 before being diagnosed with can cer. Fourteen cases (61%) and 34 controls (49%) had been treated with azathioprine for at least 1 month after being diagnosed with MS (adjus ted odds ratio = 1.7; 95% confidence interval [CI], 0.6 to 4.6). When assessing risk associated with different durations of azathioprine the rapy compared with no treatment at all, we found that MS patients had an increase in cancer risk of 1.3 (95% CI, 0.4 to 4.0) when treated le ss than 5 years, of 2.0 (95% CI, 0.4 to 9.1) when treated 5 to 10 year s, and of 4.4 (95% CI, 0.9 to 20.9) when treated more than 10 years. S imilar results were obtained when assessing cancer risk associated wit h cumulative doses of azathioprine ever taken. This case-control study suggests that the overall long-term risk of cancer from azathioprine is low in MS patients. The results are suggestive of a dose-response r elationship with no significant risk during the first years of treatme nt and a possible increased risk after about 10 years of continuous th erapy. Further studies are needed to better assess the risk-benefit ra tio of azathioprine in MS.