Comparison between clinical trials and real-world evidence studies on biologics for severe asthma

Abstract

In recent years, the more widespread availability of biological drugs with specific mechanisms of action has led to significant breakthroughs in the management of severe asthma. Over time, numerous randomised clinical trials have been conducted to evaluate the efficacy and safety of these biologics and define the eligibility criteria of patients suitable for various therapeutic options. These studies were conducted under controlled conditions not always applicable to real life. For this and other reasons, real-world evidence and pragmatic studies are required to provide useful information on the effectiveness of biological drugs and their safety, even in the long term. Because differences in outcomes have sometimes emerged between clinical trials and real-life studies, it is important to clarify the causes of these discrepancies and define the significance of the results of studies conducted in the course of daily clinical practice. Thus, a scientific debate is ongoing, and no consensus has been reached. The purpose of this narrative review is to analyse the differences between randomised trials and real-world evidence studies, focusing on their roles in guiding clinicians among different therapeutic options and understanding the reasons for the large discrepancies often found in the results obtained.

Real-world outcomes of mepolizumab for the treatment of severe eosinophilic asthma in Canada: an observational study

“…A global, prospective, observational cohort study, REALITI-A, showed that real-world rates of CSEs were reduced by 71% with mepolizumab treatment, as were exacerbations requiring hospitalizations and/or ED visits (76% reduction), while median daily oral corticosteroid (OCS) dose (in patients using maintenance OCS) decreased by 75% (10 mg/day to 2.5 mg/day) after 1 year of treatment [ 6 ]. Further studies have supported these findings, including the real-world REDES study in Spain, where mepolizumab reduced CSEs in patients with SA-EP by up to 77.5% compared to baseline [ 7 – 9 ]. Whilst a strength of REALITI-A was its multi-national study design, evaluation in a variety of real-world populations within different healthcare systems is invaluable.…”

Baseline Characteristics of Patients Enrolled in Clinical Trials of Biologics for Severe Asthma as Potential Predictors of Outcomes

“…Asthma is a disease characterised by a great heterogeneity of immunological pathways and clinical manifestations, and it requires an approach based on personalised medicine and the study of phenotypes and endotypes [ 1 , 2 ]. Over the past 20 years, biological drugs have been developed for the treatment of severe refractory asthma, with numerous randomised controlled trials (RCTs) conducted to define their safety and efficacy [ 3 ]. These drugs have targeted mechanisms of action and are addressed to specific patients, albeit there is a certain degree of overlap regarding their inflammatory characteristics—especially those with type 2 (T2)-high asthma.…”

Omalizumab Transitions in Severe Asthma: Factors Influencing Switching Decisions and Timing for Optimal Response

“…Omalizumab works by inhibiting the interaction between human IgE and the high- and low-affinity receptors [ 8 ]. Numerous studies have demonstrated the effectiveness of omalizumab in improving different clinical parameters of severe asthma and providing better control of disease exacerbation and airflow obstruction [ 9 – 11 ]. However, some patients have a poor response to omalizumab and require alternative biologic therapies [ 12 , 13 ].…”