Prolonged azathioprine treatment of non-remitting multiple sclerosis

Abstract

SUMMARY Two groups of 85 and 42 ambulatory patients with moderately advanced nonremitting multiple sclerosis were treated for six to 14 and three to six years with daily azathioprine. Less than 10% of these patients became confined to a wheelchair. This far exceeds any possible result in a group of non-remitting multiple sclerosis patients not so treated.There has been convincing evidence for at least a partial role of immune mechanisms in the production of multiple sclerosis for many years. These data still seem relevant despite the great proliferation of other data relating to the pathogenesis of this disease (Jersild et al., 1972; Lancet leaders, 1974 Lancet leaders, , 1976Miyamoto et al., 1976). In the mid 1960s the exact nature of the immunological mechanisms of multiple sclerosis were unclear. However, it seemed reasonable to attempt chronic immunosuppressive therapy with agents more potent and reliable than corticosteroids and ACTH, analogous to the data from experimental allergic encephalomyelitis (Hoyer et al., 1962;Paterson and Drobish, 1969;Vogel and Calabresi, 1969). Therefore, patient selection criteria and a chronic treatment protocol using purine analogues were established in 1964 and continued to the present. This report mainly concerns the effect of this treatment on patients with non-remitting multiple sclerosis treated for a minimum of six years. The study was under way for several years before the efficacy of this treatment was realised. When All patients with probable or definite multiple sclerosis by the criteria of Schumacher et al. (1965) and defective colour vision (Rosen, 1965) were considered for the study. In the first series, 48 of the patients were women, 37 were men. Thirtythree were between 25 and 35 years of age, and 52 were in the 35 to 45 year age group at the onset of treatment with azathioprine. All the patients had had the disease, by history, for at least four years. At the time of their inclusion in the study they had all shown objective evidence of worsening of their disease in the previous year. Patients with a static course for over one year before consideration for the study were excluded; so were those patients with a remission within three years of the study.The average patient in this pilot study of 85

Double blind controlled randomized study on azathioprine efficacy in multiple sclerosis. Preliminary results

“…Merfin's [6] arid Zeeberg's [15] studies may explain the lack of difference between treated and control cases reported in their papers. However, in agreement with Rosen's [10] impressive results (9% of the treated vs 65% of the controls deteriorated after 4.5 years of therapy), we did notice a decreasing trend of the PR in our progressive immunosuppressed patients. However, in agreement with Rosen's [10] impressive results (9% of the treated vs 65% of the controls deteriorated after 4.5 years of therapy), we did notice a decreasing trend of the PR in our progressive immunosuppressed patients.…”

“…Empirical results drawn from other studies are not conclusive for clinical efficacy of this drug in MS, mainly because only 2 previous studies have been performed with controlled double-blind methodology [15,6]. This result would be consistent with the data of Rosen [10], Ellison [3] and Patzold [9], although the last named finds a therapeutic efficacy since the trLrst year of therapy, and only in relapsingprogressive cases. This result would be consistent with the data of Rosen [10], Ellison [3] and Patzold [9], although the last named finds a therapeutic efficacy since the trLrst year of therapy, and only in relapsingprogressive cases.…”

“…Many studies have been conducted since then to evaluate its efficacy in MS, with different results and scant comparability because of differences in methodology and clinical conditions (patients selection, treatment duration and assessment of efficacy) [3,7]. The controlled studies suggest a benefit in the progressive form of the disease [10,9,3] not confirmed, however, by Zeeberg's double blind trial [15], while no effect has been found in relapsing-remitting (RR) MS [13,6]. We report a double blind controlled trial of Azathioprine in MS and try to assess the efficacy of this therapy both in the progressive and RR forms of the disease.…”

Some Recent Advances in the Clinical Aspects of Multiple Sclerosis

“…Adequate immuno-suppression is still difficult to achieve without side effects and longer follow-up studies are required. The results of one such study with Azothiaprine (Rosen, 1979) are encouraging. Two groups of ambulatory patients with moderately advanced non-remitting MS were treated for 6-14 and 3-6 years with Azothiaprine and less than 10% of these patients became confined to a wheelchair over the period of the study which was considerably fewer than would have been expected from the natural history of the disease.…”