In this issue of theEuropean Respiratory Journal, Judsonet 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].
Given the clear rationale for testing these therapies in sarcoidosis, it is disappointing that neither therapy showed clinical benefit assessed by either primary or secondary end-points. These negative results follow a large trial of infliximab by many of these same investigators. In a randomised, placebo-controlled trial of infliximab in pulmonary sarcoidosis by Baughmanet al.[4], there was a statistically significant 2.5% increase in forced vital capacity (FVC) % predicted with infliximabversusplacebo and no significant differences for any of the major secondary end-points at 6 months. Although the authors suggest this was a robust response, healthcare payers (both corporations and governments) concluded that infliximab demonstrated only minimal improvement for patients with pulmonary sarcoidosis and cite this research as a reason to deny coverage of this therapy. Several studies find infliximab beneficial for progressive nonpulmonary manifestations of sarcoidosis [5,6], but in aggregate, these studies have not led to regulatory approval for infliximab in sarcoidosis in either Europe …