Optimisation of cyclophosphamide therapy in systemic vasculitis.
Richmond R., McMillan TW., Luqmani RA.
There is no doubt that the prognosis for systemic vasculitides has been considerably improved by the use of immunosuppressive agents, chiefly cyclophosphamide. Increasingly, we are becoming aware of the enormous burden of chronic 'grumbling' disease, the high incidence of relapse and the longer term effects of toxic therapy in these patients. The general approach is more intense therapy (with intermittent high dose 'pulses' or lower dose continuous cyclophosphamide) in the initial phase of therapy to induce remission, followed by a less toxic therapy in the maintenance phase (either longer intervals between pulses or a switch to a less toxic drug, such as azathioprine). The pathogenetic mechanisms in vasculitis, which are becoming more precisely defined, are diverse, but cyclophosphamide remains the drug of choice. A number of different cyclophosphamide regimens are in use, which reflects the current dilemma of trying to balance effectiveness with toxicity in diseases where the quality of long term survival remains unsatisfactory. Evidence from controlled trials does not support major differences in immediate outcome between different regimens of cyclophosphamide. Future studies need to address the use of agents designed to interfere precisely with the underlying pathogenetic mechanisms. Alternative approaches should also be considered, for example the use of sublethal doses of cyclophosphamide, with autologous bone marrow rescue, which may achieve long lasting remission or even cure.