ERS 2024: Anti-inflammatory Reliver in Clinical Practice in Asthma: How to Implement in the Background of GINA
Speaker- Anneke ten Brinke
Anti-inflammatory relievers in asthma and why Global Initiative for Asthma (GINA) and the recent European Respiratory Society (ERS) guidelines recommend transitioning from short-acting β2-agonist (SABA) to a combined inhaled corticosteroid (ICS)-formoterol regimen as a reliever across all treatment steps. The rationale behind this recommendation, with potential limitations and challenges that may necessitate alternative strategies and implementing this new approach in clinical practice.
Recent GINA reports recommended a major shift, advocating for ICS-formoterol as a reliever for all treatment steps, replacing SABA. Historically, SABAs have been used since the 1950s for quick relief and recommended as needed for mild asthma, while ICSs were used for more severe cases. However, adherence to ICS therapy has been challenging due to the lack of immediate relief and concerns about long-term side effects. As a result, many patients over-rely on SABAs, leading to frequent overuse. This overuse has been linked to an increased risk of severe exacerbations and mortality, likely due to uncontrolled asthma and inadequate ICS use rather than the SABAs themselves.
A new strategy, known as the anti-inflammatory reliever strategy, was introduced, combining ICS with a rapid bronchodilator to ensure ICS is used when patients experience symptoms indicative of underlying inflammation. This approach, starting with moderate to severe asthma, is known as Maintenance and Reliever Therapy (MART). MART uses ICS-formoterol as both maintenance and reliever therapy. Evidence supporting MART is robust, demonstrating a 30% reduction in exacerbations. Cost-effectiveness studies validate its efficiency, and it has been approved in over 120 countries, showing effectiveness across various asthma subtypes.
GINA guidelines recently extended the use of ICS-formoterol as both maintenance and reliever therapy from steps three to five to steps one and two, replacing SABA for all patients. This shift was driven by concerns about SABA overuse and emerging evidence showing ICS-formoterol's effectiveness in reducing severe exacerbations across all asthma severities, including mild asthma. Studies indicated that for step two patients, ICS-formoterol as needed was at least as effective as maintenance ICS-formoterol combined with SABA, but with a lower ICS dose and a better risk-benefit profile. Additionally, patients generally preferred this approach of using medication as needed.
Although GINA's recommendations are influential, they are not official regulations and have not yet been approved in several countries, including the U.S. and the European Union. In response, the ERS established a task force to develop guidelines based on a systematic review, known for its robustness and transparency. The resulting recommendations align with GINA, advising that patients with mild asthma use ICS-formoterol as needed instead of SABA. The ERS also recommended adopting this strategy over regular ICS maintenance with SABA for all treatment steps.
In the GINA guidelines, ICS-formoterol was recommended as a low-dose reliever for steps one and two to prevent dependence on SABA and simplify treatment escalation to MART if needed. For steps three through five, patients were advised to use ICS-formoterol as both maintenance and reliever therapy in the same inhaler, avoiding additional SABA to maintain the effectiveness of the MART approach. ICS-formoterol was highlighted as the only ICS- long-acting β2 agonist (LABA) combination suitable for use as an anti-inflammatory reliever. Switching from other ICS-LABA combinations to ICS-formoterol was recommended, as combining different ICS-LABA products could increase side effects. While most data supporting these guidelines came from budesonide-formoterol studies, GINA suggested that beclomethasone-formoterol might also be effective, though this evidence was indirect. A maximum of 12 doses per day was advised based on safety data.
The feasibility of introducing this strategy was questioned due to several challenges. In low- and middle-income countries, despite World Health Organisation (WHO) recommendations, access to ICS-containing medications was limited. Even in wealthier countries, issues with regulatory rules and insurance coverage created difficulties in aligning with recent guidelines, complicating implementation in clinical practice.
Alternatives to the traditional approach were explored in the study. One alternative involved instructing patients to use an ICS in a separate inhaler when they needed a SABA, which also resulted in reduced exacerbations. However, this method presented challenges, such as the inconvenience of managing two inhalers and the need to assess real-world compliance. Another option was the use of an ICS-SABA combination, specifically Albuterol-budesonide, which proved more effective than a SABA alone in reducing exacerbations in patients with moderate to severe asthma. Albuterol-budesonide received Food and Drug Administration (FDA) approval for this specific use.
GINA provided an alternative strategy for situations where the preferred Track 1 was not feasible, such as when ICS availability was limited, or patients were well-controlled with no exacerbations and adherence to ICS maintenance was problematic. This alternative approach involved using an ICS-SABA combination or a SABA with other maintenance inhalers. However, SABA monotherapy was discouraged, and it was recommended that ICS be used whenever a SABA was taken.
There was limited data on the use of these strategies in children and uncertainty about their effectiveness and necessity for all patients. Questions arose about the risk of undertreatment in poor perceivers and the applicability for patients on biologics or in emergency settings. Additionally, there was a need to evaluate the effectiveness of other ICS-Formoterol or ICS-SABA combinations and devices, and to conduct cost-effectiveness studies for mild cases. The implementation of Anti-Inflammatory Reliever (AIR) strategies faced several challenges within the healthcare network. Regulatory bodies and insurance played crucial roles in access and cost, while a comprehensive understanding and alignment among all healthcare providers were essential for consistent patient information. Healthcare professionals encountered barriers such as knowledge gaps, guideline confusion, reluctance to change, and time constraints. Patients’ acceptance of ICS-Formoterol as needed was generally positive, though some expressed concerns about its perceived slower effect compared to SABA. Long-term SABA users faced difficulties in adjusting to the new approach. Dry powder inhalers also posed challenges during severe symptoms. Effective communication and education were deemed critical for patient adaptation and ensuring individualized care.
Considering the barriers to implementation, it was crucial to identify and address them, as they could vary significantly depending on location and country. Successful implementation required an understanding of these barriers. National guidelines were considered valuable as they could outline feasible AIR strategies within a specific country and ensure appropriate approvals. Such guidelines could eventually lead to the development of treatment algorithms and AIR asthma action plans, facilitating the integration of new strategies into practice.
In an ideal world, implementing the AIR approach for all patients would be ideal, but starting with specific subgroups remain practical. The focus should be on new asthma diagnoses to introduce the AIR approach early and avoid future complications. In the practice, patients with new, mild asthma were initially given ICS-Formoterol twice daily for three months, with reassessment for possible transition to as-needed medication. High-risk patients, such as those with high SABA use or frequent emergency room visits for asthma, were targeted. They could be identified through clinical visits or prescription data, and then managed with improved inhalation techniques and collaboration to transition to an AIR approach.
As the era of AIR strategies began, GINA and recent ERS guidelines recommended replacing SABA with ICS-Formoterol as a reliever in all treatment approaches. However, full implementation in practice requires addressing significant challenges. Researchers should close the knowledge gaps, while the pharmaceutical industry need to be encouraged to provide more affordable ICS-Formoterol combinations globally. Doctors need to adapt their practices, educate colleagues, and inform patients to facilitate this transition.
The new strategy also offered significant environmental benefits, particularly when using dry powder inhalers. Recent studies indicated that carbon footprints could be reduced by 95% with as-needed ICS-Formoterol dry powder compared to traditional treatments. This approach represented a dual win for both patients and the planet, highlighting the importance of adopting this environmentally friendly option.
European Respiratory Society Congress 2024, 7–11 September, Vienna, Austria
