Good symptom control achievable in most asthma patients

New options for modern asthma therapy in adults based on the recently published new asthma guideline of the German Respiratory League were presented in Cologne.

“Crucial to good asthma therapy is early and correct diagnosis of the disease,” Buhl said. However, there are still certain problems here, especially in the non-specialist sector, for example indications of overdiagnosis of asthma. In one study, about one in three patients with a doctor’s diagnosis of asthma failed to confirm the disease when checked with pulmonary function tests, nonspecific provocation, and gradual reduction of antiasthmatic medication, Buhl reported. He reminded that spirometric pulmonary function measurement (before and after bronchodilation) and methacholine provocation were necessary for asthma diagnosis (possible under continuous anti-inflammatory medication!). These two tests could diagnose or rule out the disease in 90% of patients with suspected bronchial asthma.

In addition, allergy diagnostics and, especially in severely ill patients, the measurement of eosinophils in the blood to detect eosinophilic asthma should not be forgotten. According to Buhl, indications of allergic asthma include early onset of disease, allergic comorbidities such as rhinoconjunctivitis, allergen-related symptomatology, and elevated IgE levels. A late onset of disease, frequent symptoms and exacerbations, and no relevant allergy are indicative of eosinophilic asthma. Many of these patients also have nasal polyps and impaired sense of smell and taste.

“Allergic asthma has been on the rise for decades,” Buhl reported. According to cross-sectional surveys in Sweden, asthma prevalence in adults has increased from just over 8% in 1996 to more than 10% in 2016. This was mainly due to more frequent allergic asthma, while the proportion of non-allergic asthma remained constant at just under 4%.

German step-by-step plan according to international GINA recommendations

The current asthma staging plan in the new German asthma guideline, which was published at the end of last year [1], essentially follows the international GINA (“Global Initiative for Asthma”) recommendations. Asthma therapy is known to be divided into five stages, which also determine asthma severity: mild asthma means good asthma control (in adults ≤2 symptoms/week during the day and symptom-free at night) at therapy levels 1 and 2, moderate asthma corresponds to levels 3 and 4, and severe asthma level 5.

Like GINA, the experts of the German Respiratory League recommend considering long-term therapy with low-dose inhaled corticosteroids (ICS) already in patients with mild asthma and rare symptoms (stage 1). “The prerequisite is that the patient also wants to play along,” Buhl said. There is evidence to support this therapeutic approach, but the benefit is only moderate, he said. “According to the study data, you need to treat ten patients with 200-400 µg of budesonide daily for ten years to prevent a serious event,” the pulmonologist said. Patient mortality was not reduced. For many patients in this group, therefore, ICS would be “somewhat of an overtreatment,” Buhl said.

The standard of care is low-dose ICS therapy in patients with mild asthma who require demand therapy with short-acting beta-2 mimetics (SABA) more frequently than twice a week or who have nighttime symptoms (level 2). Oral leukotriene receptor antagonists (LTRA, e.g., montelukast) are mentioned as an alternative. If this is not sufficient for good symptom control, combination therapy with ICS and long-acting beta-2 mimetics (LABA) should be given – at a low dose (level 3), and at a medium to high dose (level 4) if response is insufficient. The last step is the addition of the anticholinergic tiotropium (also already an option at level 4) and additional antibody therapy with anti-IgE (omalizumab) in severe allergic or with anti-interleukin-5 (mepolizumab, reslizumab, benralizumab) in severe eosinophilic asthma. Continuous therapy with oral corticosteroids, even at low doses, should be avoided if possible, Buhl emphasized.

Step therapy should be escalating or de-escalating depending on symptom control. In addition, in adult patients with allergic asthma and allergic rhinitis who are uncontrolled despite ICS therapy (stages 3-4), specific immunotherapy should be considered, Buhl said. The prerequisite is a one-second value (FEV1) >70%. The efficacy of allergen-specific immunotherapy was again documented in two systematic literature reviews and a meta-analysis [2,3].

In patients with severe allergic asthma treated with omalizumab, current studies indicate that therapy must be sustained for sustained good symptom control. The omalizumab effect persists in patients with severe allergic asthma on long-term therapy. When the antibody is discontinued, Buhl estimates that at least half of those treated experience a significant increase in symptoms again.

Omalizumab is well tolerated; anaphylactic reactions are the only relevant side effects, according to Buhl. However, only 0.2% of those treated were affected, and anaphylaxis usually occurred within two hours of the first three injections. Buhl’s advice is to follow up with patients in the office for two hours for the first three treatments and 30 minutes for each additional treatment. Thus, three quarters of all anaphylactic reactions could be well controlled.

Whether interleukin (IL)-5 blockers are considered for patients with eosinophilic asthma depends on the degree of eosinophilia. The cutoff value is an eosinophil count ≥300/µl of blood in two separate measurements, Buhl reported. “As eosinophilia increases in the blood, the chance that patients will respond to these medications increases,” the pulmonologist said, meaning that the risk of exacerbation can be significantly reduced. According to the experience to date, all three available Anit-IL-5 antibodies are more or less equally effective. The application and therapy cycles are somewhat different. Mepolizumab (s.c.) and reslizumab (i.v.) must be used every four weeks, benralizumab (s.c.) only every eight weeks.

“The success story of antibody therapy in patients with severe bronchial asthma will continue,” Buhl said. In the pipeline are two anti-IL-13 antibodies (lebrikizumab, tralokinumab) and the anti-IL-4/IL-13 antibody dupilumab, which is already approved in atopic dermatitis. Buhl also cited the anti-TSLP (thymic stromal lymphopoietin) antibody, which has been successfully tested in phase II trials in patients with uncontrolled asthma, as a promising approach.

Last-not-least, in patients with severe asthma in whom all else has failed, there are still several options for off-label use, including antifungals, macrolides, methotrexate, and bronchial thermoplasty. So, all in all, there are a lot of options to control asthma to a large extent in (almost) all patients.

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