Combination therapy: the risks of infection and tumor induction.

It is clear that the rate of infection is increased in most of the more serious forms of autoimmune disease and agents such as high-dose steroids and the alkylating agents increase this risk. Other agents such as MTX, CsA, LEF, AZA and the TNF antagonists do not appear to increase the risk of infection given either alone or in combination. Similarly, the risk of malignancy in certain types of autoimmune disease appears increased. However, other than the alkylating agents, none of the agents used appear to increase this risk. The more recently released agents such as CsA, LEF and the TNF antagonists need longer durations of follow-up to substantiate this, however. It is clear that, unless they are absolutely necessary, one should avoid the alkylating agents used either alone or in combination to avoid problems with infection and malignancy. In addition, the use of steroids should be kept as low as possible to avoid infections. It is possible that the use of the more benign agents alone and in combination earlier in the disease course may help to reduce both infection and the incidence of malignancy in the long run.