Negative clinical trials in sarcoidosis: failed therapies or flawed study design?

In this issue of the European Respiratory Journal, JUDSON et al. [1] report the results of a large clinical trial involving two new potential therapies in sarcoidosis, a subcutaneous anti-tumour necrosis factor (TNF) agent, golimumab, and a novel anti-p40 (a component of both interleukin (IL)-12 and IL-23) agent, ustekinumab. The rationale for the use of anti-TNF agents in sarcoidosis is compelling, as TNF plays a central role in granuloma formation [2]. The use of anti-p40 (anti-IL-12/IL-23) also has a solid rationale based on the role of IL-12 in promoting T-helper (Th) type 1 immune responses and its upregulation in sarcoidosis. The role of the IL-23/Th17 pathways in sarcoidosis is less well established but the benefits of blocking IL-23 together with IL-12 is conceptually appealing in sarcoidosis [3].