I am grateful to Drs. Salvarani and Hunder for raising the issue that their studies of infliximab in polymyalgia rheumatica and GCA were not designed to test a small treatment effect of the agent above that achieved from corticosteroid alone. If there is only a small treatment effect, a cost–benefit analysis is likely to conclude that infliximab does not have a clinically or statistically significant role in the management of polymyalgia rheumatica or GCA. If, on the other hand, the study demonstrated that severe complications, such as sight loss in GCA, could be prevented or that steroid toxicity could be avoided by using much lower doses of steroid, these would be more compelling reasons to reconsider the use of this agent in these diseases.

There is a separate question about whether infliximab has a role in the management of patients who have relapsing or resistant disease, in whom the authors point out that benefits have been seen, albeit in pilot studies. Reduction in IL-6 levels as a result of suppressing TNF and associated with clinical benefit would suggest that a more direct attack on IL-6 might be more logical, especially because the persistence of IL-6 in temporal biopsy specimens is predictive of disease persistence. There would certainly be support for a study looking at the management of resistant polymyalgia rheumatica and GCA with anti-TNF therapy or anti–IL-6 therapy.

We may be able to identify at onset patients in whom standard therapy with corticosteroids is likely to fail and stratify them to receive additional anti-TNF or anti–IL-6. It is becoming more realistic to perform cytokine profiles in clinical practice and thereby identify patients who are most likely to require more aggressive therapy and those who may benefit from much milder therapy. In the control groups for these 2 studies, several patients responded well to short-duration corticosteroid therapy.