Azathioprine In Multiple Sclerosis Research Articles

Cancer risk and mortality in multiple sclerosis: The need for vigilance

Several investigators have addressed the possibility of a link between cancer and multiple sclerosis (MS). The consensus view favours an increased risk, but analysis is compromised by multiple confounders, including small sample sizes, age and socio-economic group of the population in question, level of education and whether a cancer diagnosis was based on the less reliable death certificates compared to cancer registries. Coupled with this is the problem of subsequent cancer-related mortality in those with MS compared to those without MS. Until 1996 patients were treated chiefly with steroids, azathioprine, cyclophosphamide and occasionally mitoxantrone. Each of these has its own potential long-term risk of cancer probably least of all with steroids. Mitoxantrone has a small but definite risk of acute myeloid leukaemia particularly if patients are exposed to more than 60mg/M2 ( Lebrun and Rocher, 2018 Lebrun C Rocher F. Cancer risk in patients with multiple sclerosis: potential impact of disease-modifying drugs. CNS drugs. 2018; 32 (Oct): 939-949 Google Scholar ). Azathioprine is connected with a particularly high rate of non-Hodgkin lymphoma in renal transplant cases ( Kinlen, 1992 Kinlen L. Immunosuppressive therapy and acquired immunological disorders. Cancer research. 1992; 52 (Oct 1): 5474s-5476s Google Scholar ) but this has not been found for large studies in MS that had a follow-up range of <10 years and a total dose exposure of no more than 600g ( Casetta et al., 2007 Casetta I Iuliano G Filippini G. Azathioprine for multiple sclerosis. Cochrane Database of Systematic Reviews. 2007; Google Scholar ).

Experience in using azathioprine for multiple sclerosis in developing country: A preliminary study

Background Incidence of multiple sclerosis has recently increased in developing countries, including Indonesia. Currently FDA-approved drugs for modifying disease are still expensive and not covered by insurance in Indonesia. Therefore Azathioprine is promising as alternative treatment to prevent and reduce relaps of multiple sclerosis in developing country. Aim To evaluate the use of azathioprine in multiple sclerosis and review the relevant literature Methods Three patients treated with azathioprine 0.7–2.5 mg/kg per day for 24 months were evaluated in a retrospective follow-up study. Results Two patients were free from relaps during two years treatment with Azathioprine. One patient suffered from relaps after tapering off of Azathioprine (after two years treatment). Side effects were few and were well-tolerated. Hematologic profile was unremarkedly influenced. Conclusion Azathioprine might be an effective and cheaper alternative in the treatment of multiple sclerosis, especially in developing country. Long-term use might be needed to prevent or minimize relaps of multiple sclerosis, but its long-term toxicity remains unclear.

Commentary on “Azathioprine for multiple sclerosis”

This systematic evaluation of a well established inexpensive drug whose short term effects appear similar to those of newer agents, but …

Azathioprine for multiple sclerosis

Background:Azathioprine (AZA) is an immunosuppressive drug widely prescribed for the treatment of multiple sclerosis (MS) until the first half of the 1990s. It could be an alternative to interferon β...

Azathioprine for multiple sclerosis

Azathioprine for multiple sclerosis

Azathioprine in Multiple Sclerosis

Azathioprine is an immunosuppressive and steroid-sparing purine analogue, used in the treatment of several autoimmune diseases. In multiple sclerosis, available evidence suggests that oral azathioprine reduces relapse rates, provides a slight benefit on disability, and reduces new inflammatory lesions. Here, we focus on molecular mechanisms of Azathioprine and on its usefulness in multiple sclerosis.

Azathioprine for multiple sclerosis.

Azathioprine is the most widely used immunosuppressive treatment in multiple sclerosis (MS). It is an alternative to interferon beta for treating MS also because it is less expensive. Concerns about its safety, mainly a possible increased risk of malignancy, has limited its use. This systematic review aimed to determine the trade off between the benefits and risks of azathioprine in multiple sclerosis. To compare azathioprine versus placebo. To determine the effect of azathioprine on major clinical outcomes, i.e., disability progression and relapses in patients with multiple sclerosis. The Multiple Sclerosis Group's Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL- Issue 4, 2006), Cochrane Database of Systematic Reviews (CDSR - Issue 4, 2006), Database of Abstracts of Reviews of Effectiveness (DARE - searched 28.12.06) MEDLINE (PubMed) (1966 to December 2006), EMBASE (1980 to December 2006). Journals and reference lists were hand searched for relevant articles both to benefit and adverse effects. Regulatory agencies were additional sources of information for adverse effects. All parallel group randomised controlled trials (RCTs) comparing azathioprine treatment of a least one year duration with placebo for patients with multiple sclerosis. Cohorts, case controls, case series and case reports were also used to assess adverse effects. Potentially relevant references were evaluated and all data extracted by two independent authors. The five trials that met our criteria included 698 randomised patients: data from 499 (71.5%) were available for analysis of relapse frequency in patients at one year's, from 488 (70%) at two years' and from 415 (59.5%) at three years' follow-up. Azathioprine reduced the number of patients who had relapses during the first year of treatment (relative risk reduction [RRR] =20%; 95% CI = 5% to 33%), at two years' (RRR =23%; 95% CI = 12% to 33%) and three years' (RRR =18%; 95% CI = 7% to 27%) follow-up. These results were consistent in sensitivity analysis. There was no heterogeneity among the studies. Data from only three small trials with a total of 87 patients were available to calculate the number of patients who progressed during the first two to three years. There was a statistically significant benefit (RRR = 42%; 95% CI = 7% to 64%) of azathioprine therapy at three years' follow-up; this result was robust after sensitivity analyses and there was no heterogeneity among the trials. Gastrointestinal disturbances, bone marrow suppression and hepatic toxicity were greater in the azathioprine group rather than in the placebo group; they were anticipated, and, by monitoring and dosage adjustment, were easily managed. Withdrawals due to adverse effects were few, occurring mostly during the first year of azathioprine treatment and mainly due to gastrointestinal intolerance (5%). Data from the trials and from cohort and case controls studies available in the literature did not show an increase in risk of malignancy from azathioprine. A possible long-term risk of cancer from azathioprine may be related to a treatment duration above ten years and cumulative doses above 600 g. Azathioprine is an appropriate maintenance treatment for patients with multiple sclerosis who frequently relapse and require steroids. Cumulative doses of 600 g should not be exceeded in relation to a possible increased risk of malignancy. Considering the trade off between the benefits and harms, azathioprine is a fair alternative to interferon beta for treating multiple sclerosis. A logical next step for future trials would seem the direct comparison of azathioprine and interferon beta. In fact the direct comparison between these two widely used treatments in multiple sclerosis has not been made.

Combined Immunoglobulin and Azathioprine in Multiple Sclerosis

In an attempt to prevent exacerbations of multiple sclerosis, immunoglobulin therapy was combined with azathioprine (AZA). Intravenous immunoglobulin (IVIG) 2 g/kg was given in divided doses over 3 consecutive days followed by monthly booster doses (0.2 g/kg) for 3 years to 38 patients with relapsing-remitting multiple sclerosis (MS). In the 34 patients who completed the trial, the relapse rate decreased (from 1.7 relapses per year to 0 during the 3-year trial period). The Kurtzke Expanded Disability Status Scale decreased from 3.4 ± 0.72 to 3.0 ± 0.70. The results suggest that combined IVIG and AZA suppress the ongoing pathologic process in relapsing-remitting MS.

New treatments and azathioprine in multiple sclerosis

Several new drug treatments to reduce the relapse rate in multiple sclerosis (MS) have recently emerged. 1 Johnson KP Brooks BR Cohen JA et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicentre, double-blind, placebo-controlled trial. Neurology. 1995; 45: 1268-1276 Crossref PubMed Scopus (1776) Google Scholar , 2 Jacobs LD Cookfair DL Rudick RA et al. Imtramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996; 39(3): 285-294 Crossref Scopus (2358) Google Scholar , 3 The IFNB Multiple Sclerosis Study GroupInterferon beta-1b is effective in relapsing-remitting multiple sclerosis. Clinical results of a multicenter, randomised, double-blind, placebo-controlled trial. Neurology. 1993; 43: 655-661 Crossref PubMed Google Scholar , 4 Fazekas F Deisenhammer F Strasser-Fuchs S Nahler G Mamoli M for the Austrian Immunoglobulin in Multiple Sclerosis Study GroupRandomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Lancet. 1997; 349: 589-593 Summary Full Text Full Text PDF PubMed Scopus (386) Google Scholar These drugs are expensive, have to be given by injection, their long-term side-effects are not yet known, and definite evidence of a clear effect on progression of disability is lacking. The use of magnetic resonance imaging (MRI) to study disease activity in recent trials may have been important in the licensing of new drugs. The pharmaceutical industry has also strongly promoted relapse-reduction as an important treatment outcome in MS.

Ciclosporin A versus Azathioprine in Multiple Sclerosis—Sevenyears follow-up and longterm side effects: J Haas, E stark, U Wurster, U Patzold, D Dommasch, L Kappos, S Poser

Ciclosporin A versus Azathioprine in Multiple Sclerosis—Sevenyears follow-up and longterm side effects: J Haas, E stark, U Wurster, U Patzold, D Dommasch, L Kappos, S Poser

A long-term double-blind controlled study on the effect of azathioprine in the treatment of multiple sclerosis

The results are reported of a small double-blind controlled trial on the effect of azathioprine in multiple sclerosis. Although a trend in favour of the treated group, as regards the effect on the disability, was found, it did not reach statistical significant levels. No influence was found on the relapse rate. The influence of side-effects, which were found in the treated group in a higher percentage than in the placebo group, on the results is discussed.