Risk of cancer from azathioprine therapy in multiple sclerosis

Abstract

An increased risk of cancer has been reported in patients treated with azathioprine. To assess the long-term risk of neoplasia in azathioprine-treated multiple sclerosis (MS) patients, we conducted a case-control study using the Lyon Multiple Sclerosis Database. From the 1,191 MS patients included in the database, we identified patients who developed cancer before December 31, 1991. Each case was then matched to three cancer-free MS controls by gender, date of birth, and date of MS onset. A matched analysis was performed to compare cases and controls for exposure to azathioprine therapy during the same follow-up period. Twenty-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 followed up for an average 13.8 years +/- 8.1 before being diagnosed with cancer. Fourteen cases (61%) and 34 controls (49%) had been treated with azathioprine for at least 1 month after being diagnosed with MS (adjusted odds ratio = 1.7; 95% confidence interval [CI], 0.6 to 4.6). When assessing risk associated with different durations of azathioprine therapy 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 less than 5 years, of 2.0 (95% CI, 0.4 to 9.1) when treated 5 to 10 years, and of 4.4 (95% CI 0.9 to 20.9) when treated more than 10 years. Similar results were obtained when assessing cancer risk associated with 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 relationship with no significant risk during the first years of treatment and a possible increased risk after about 10 years of continuous therapy. Further studies are needed to better assess the risk-benefit ratio of azathioprine in MS.

Myasthenia gravis in children: analysis of 18 patients

“…Out of the few options (azathioprine, ciclophosphamide, cyclosporine) we chose azathioprine for its efficacy and safety. There is a very low risk for developing cancer in patients taking azathioprine for up to 20 years 31,32 .…”

Chemotherapeutics in the treatment of multiple sclerosis

“…The major safety concern with chronic azathioprine treatment is the increased risk of non-Hodgkin lymphoma or other malignancies during long-term use (i.e. after approximately 510 years) [Confavreux et al 1996;Lhermitte et al 1984]. Evidence indicates that this risk may be dose related and significant with cumulative doses >600 g [Casetta et al 2007].…”

Role of Immunosuppressive Therapy for the Treatment of Multiple Sclerosis

“…For example, in the British and Dutch trial [60] 26 % of patients were leukopenic at the end of year 1, while only 8 % were leukopenic at the end of year 3. There is debate about whether long-term azathioprine use predisposes to cancer [61][62][63]. Lhermitte et al [61] followed 131 patients over about 10 years and identified 10 cancers, while age-and sex-matched controls developed only 4 cancers.…”

“…Reported cancers were solid tumors rather than hematologic. A case control study undertaken using the Lyon MS database [62] found that 14 patients from a database of 1191 patients developed cancer. Risk of developing cancer with over 5 years of azathioprine treatment was double that in patients not treated with azathioprine, and more than 4-fold higher when treated for more than 10 years.…”