Infections in the Era of Targeted Therapies: Mapping the Road Ahead.

Immunosuppressive treatment strategies for autoimmune diseases have changed drastically with the development of targeted therapies. While targeted therapies have changed the way we manage immune mediated diseases, their use has been attended by a variety of infectious complications-some expected, others unexpected. This perspective examines lessons learned from the use of different targeted therapies over the past several decades, and reviews existing strategies to minimize infectious risk. Several of these infectious complications were predictable in the light of preclinical models and early clinical trials (i.e., tuberculosis and TNF inhibitors; meningococcus; and eculizumab). While these scenarios can potentially help us in terms of enhancing our predictive powers (higher vigilance, earlier detection, and risk mitigation), targeted therapies have also revealed unpredictable toxicities (i.e., natalizumab and progressive multifocal leukoencephalopathy). Severe infectious complications, even if rare, can derail a promising therapeutic and highlight the need for increased awareness and meticulous adjudication. Tools are available to help mitigate infectious risks. The first step is to ensure that infection safety is adequately studied at every level of drug development prior to regulatory approval, with adequate post-marketing surveillance including registries that collect real-world adverse events in a collaborative effort. The second step is to identify high risk patients (using risk calculators such as the RABBIT risk score; big data analyses; artificial intelligence). Finally, the most underutilized interventions to prevent severe infections in patients receiving targeted therapies across the spectrum of immune mediated inflammatory diseases are vaccinations.