Efficacy of azathioprine on multiple sclerosis new brain lesions evaluated using magnetic resonance imaging
Massacesi L, Parigi A, Barilaro A, Repice AM, Pellicano G, et al.;
Commented by , 17 Jan 2006
Background
A number of new drugs have been developed against Multiple Sclerosis (MS) during the last decades. In this regard, several studies have shown that therapeutic intervention is most beneficial in the early and relapsing phase of the disease.
Older immunosuppressive drugs, like cyclophosphamide, methotrexate and azathioprine, have previously been tested in clinical trials, and efficacy has generally been described as insufficient. These reports have often used patients with advanced and progressive disease, as well as an inadequate dose regimen.
Aim
To evaluate the efficacy of azathioprine therapy on suppression of new brain lesions in MS.
Methods
The authors included relapsing remitting MS patients with three or more focal gadolinium-enhancing (Gd+) brain lesions in 6 previous monthly MRIs (baseline). Fourteen patients with a mean EDSS of 1.5 (1.0-3.0), disease duration 5.5 years (1-9 years) and 2 (1-4) relapses in the past two years were used. The study design was open label vs. baseline.
Patients were treated with oral azathioprine, up to 3 mg/kg/day, individually adjusted according to the lymphocyte count and occurrence of adverse events. After 6 months, a new series of 6 monthly MRIs were performed for evaluation of treatment effect. One more MRI was performed after additional 6 months (extension). The primary outcome measure was a 50% or more total Gd+ lesion number reduction between the baseline and evaluation periods and a number of secondary endpoints were also used.
Results
Gd+ lesion number and volume (p<0,001) were significantly reduced and 12 of 14 patients had a 50% reduction of Gd+ lesions (p<0.01). A similar reduction was found in new T2 lesion count (p<0.02). This effect persisted in the extension treatment period (p<0.01). Median azathioprine dose was 2.6 – 2.8 mg/kg/day, reducing the mean lymphocyte count to 57% of baseline values. Adverse events were reversible with dose adjustment.
Dr Blinkenberg's comments
The study show that a relevant immunosuppressive dose of azathioprine suppress new T2 and Gd+ enhancing lesions, and the effect seem to be close that obtained in studies of beta-interferons alone. Similar results have been shown for combination treatment with azathioprine and beta-interferon, in patients with treatment failure of beta-interferon as mono-therapy.
The current study interestingly shows, that azathioprine alone may be sufficient in the treatment of active relapsing MS.
In clinical practice it is tempting to add a second drug if the effect of first line treatment is not sufficient, although mono-therapy is preferable in any therapeutic approach.
Few studies have re-addressed the indication for using older and well-characterized immunosuppresants in early treatment of active MS, although striking results have been obtained with Mitoxantrone.
The development of new MS drugs has naturally drawn attention and interest, although the gain of using these drugs is not well characterized. Studies in this context have so far been poor, although the current study supports the incitement for further investigation.
Larger studies with a relevant randomized and placebo-controlled design is needed, which in fact is being carried out for the immunosuppressive agent Cladribine right now.