Tumor necrosis factor (TNF) is a potential therapeutic target in severe asthma. It is a proinflammatory cytokine, expressed by mast cells, eosinophils, CD4+ T lymphocytes, and alveolar macrophages. It promotes airway inflammation and hyperreactivity, as well as mucin hyperproduction. A randomized, double-blind, dose-ranging, multicenter phase 2 clinical trial (43) assessed the efficacy and safety of golimumab, an anti-TNF monoclonal antibody, in 309 patients with symptomatic severe asthma for 76 weeks. Golimumab treatment did not improve either of the co-primary end points—change in prebronchodilator FEV1 or number of severe exacerbations. Furthermore, the study was terminated early because of an unfavorable risk–benefit profile: Serious adverse events, including infections (tuberculosis, pneumonia, and death due to septic shock) and cancer (breast cancer, lymphoma, melanoma, as well as colon, renal, cervical, and basal carcinomas), occurred more frequently in the golimumab group. This shows that anti-TNF approaches are not suitable for a general population of patients with severe asthma. Furthermore, the authors concluded that the unacceptable risk–benefit ratio of golimumab therapy should preclude the initiation of additional large studies of anti-TNF therapy in this population. A post hoc subgroup analysis showed that patients with bronchodilator reversibility or sinusitis were less likely to have serious asthma exacerbations when treated with golimumab, which suggests that a subtype with physiologically defined severe asthma might be a target population if further clinical trials of anti-TNF are considered. However, any potential benefit in severe asthma would need to outweigh the risks of this approach. Additional serious toxicities associated with anti-TNF for treatment of inflammatory arthritides have included opportunistic infections, hepatitis B reactivation, demyelinating disorders, aplastic anemia, and pancytopenias (44).