Abstract:Systemic corticosteroids are no longer recommended for the treatment of severe, uncontrolled asthma. Instead, various biologics are available. When prescribing these, it is important to ensure the correct indication, select the appropriate biologic and apply the correct ICD coding.

BACKGROUND:Randomized controlled trials have shown clinical efficacy of dupilumab in patients with severe asthma. However, the long-term effectiveness of dupilumab treatment for asthma in real-life is incompletely understood. METHODS:ProVENT (NIS-Nr.: 514; study code: OBS16379) is a non-interventional, prospective, 3-year study in patients aged ≥12 years with severe asthma receiving dupilumab per routine clinical care in Austria, Germany, and Switzerland. This interim analysis of ProVENT assessed lung function, asthma control, quality of life, biomarkers, and clinical remission, over the first 2 years in the study. Safety outcomes will be presented in the final analysis. RESULTS:421 patients were screened, and of the 399 patients enrolled in ProVENT, 259 had ≥1 post-baseline assessments and 100 had documented data after 24 months of treatment. At month 24, mean (standard deviation [SD]) improvement from baseline was 0.24 L (0.46) for pre-bronchodilator forced expiratory volume in 1 s (FEV1); 10.10% (15.80) for pre-bronchodilator percent predicted FEV1;-0.96 (1.24) for 5-item Asthma Control Questionnaire score (ACQ-5); 4.4 (5.4) for Asthma Control Test score (ACT); and 0.61 [1.3] for Standardized Asthma Quality of Life Questionnaire overall score (AQLQ [S]). Blood eosinophils, fractional exhaled nitric oxide (FeNO), and total serum immunoglobulin E (IgE) decreased by month 24. Among patients with available data, clinical remission rates were 55.9% at year 1 and 58.0% at year 2. CONCLUSION:In real-world patients with severe asthma, long-term dupilumab treatment is associated with sustained improvements in lung function, asthma control, and quality of life. Nearly 60% of patients achieved clinical asthma remission after 2 years.

Hintergrund: Biologika sind Mittel der ersten Wahl bei Patienten mit schwerem, unzureichend kontrolliertem Asthma. Sie können zu einer starken Senkung (oder sogar vollständigen Vermeidung) von Exazerbationen, des Bedarfs an nebenwirkungsreichen systemischen Glukokortikoiden und zu einer deutlichen Besserung der Asthmakontrolle und der Lungenfunktion bei schwerem Asthma führen. Aufgrund der hohen Jahrestherapiekosten einer Biologika-Therapie besteht einerseits ein berechtigtes Interesse seitens der Kostenträger an einem leitlinien- und zulassungskonformen sowie wirtschaftlichen Einsatz von Biologika bei schwerem Asthma, andererseits besteht ein berechtigtes Interesse seitens der behandelnden Ärztinnen und Ärzte an einer regresssicheren Verordnung dieser Biologika. Methodik: In einer Analyse der Literatur und der Zulassungen wurde in Zusammenschau mit den Erfahrungen der beteiligten Autoren die Evidenz zur Therapie mit den für schweres Asthma zugelassenen Biologika Omalizumab, Mepolizumab, Reslizumab, Benralizumab, Dupilumab, Tezepelumab und Depemokimab zusammengetragen. Ergebnisse: Basierend auf den Leitlinien-Empfehlung und Zulassungen werden Empfehlungen für die Anwendung der genannten Biologika im deutschen Gesundheitssystem gegeben. In einer gemeinsamen Anstrengung verschiedener Fachgesellschaften (AeDA, DGP, BdP, GAN, DGAKI, GPP, GPA) wurden Dokumentationsbögen für alle für schweres Asthma zugelassenen Biologika erstellt, die als Grundlage der Dokumentation dienen können. Es wurden hierbei sowohl Bögen für die Einleitung einer Biologika-Therapie als auch Bögen zur Verlaufsfdokumentation einer Biologika-Therapie bei schwerem Asthma entwickelt. Schlussfolgerung: Die neuen Dokumentationsbögen fassen praxistauglich alle wichtigen Eckpunkte der Biologika-Verordnung und der Beurteilung des Biologika-Ansprechens bei schwerem Asthma auf einer Seite zusammen und dienen sowohl der Sicherstellung einer leitliniengerechten und zulassungskonformen Verordnung als auch der Vermeidung von Arzneimittel-Regressen. Zitierweise: Klimek L, Buhl R, Brehler R, Hamelmann E, Joest M, aufm Kampe K, Korn S, Lampert S, Mülleneisen N, Taube C, Trischler J, Vogelberg C, Schmitz F, Lommatzsch M. Position paper on the documentation of biologic therapies for severe asthma. Recommendations of the Association of German Allergologists (AeDA), the German Society for Pneumology and Respiratory Medicine (DGP), the Federal Association of Pneumology, Sleep and Respiratory Medicine (BdP), the German Asthma Net (GAN), the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Pneumology (GPP), and the Society for Pediatric Allergology and Environmental Medicine (GPA). Allergo J Int. 2026;35:65-76

Zusammenfassung Biologika sind Mittel der 1. Wahl bei Patienten mit schwerem, unzureichend kontrolliertem Asthma und können zu einer starken Senkung (oder sogar vollständigen Vermeidung) von Exazerbationen und des Bedarfs an nebenwirkungsreichen systemischen Kortikosteroiden und zu einer deutlichen Besserung der Asthma-Kontrolle und der Lungenfunktion bei schwerem Asthma führen. Aufgrund der hohen Jahrestherapiekosten einer Biologikatherapie besteht ein berechtigtes Interesse seitens der Kostenträger an einem leitlinien- und zulassungskonformen und wirtschaftlichen Einsatz von Biologika bei schwerem Asthma, andererseits besteht ein berechtigtes Interesse seitens der behandelnden Ärztinnen und Ärzte an einer regresssicheren Verordnung dieser Biologika. In einer Analyse der Literatur und der Zulassungen wurde in Zusammenschau mit den Erfahrungen der beteiligten Autoren die Evidenz zur Therapie mit den für schweres Asthma zugelassenen Biologika Omalizumab, Mepolizumab, Reslizumab, Benralizumab, Dupilumab, Tezepelumab und Depemokimab zusammengetragen. Basierend auf den Leitlinienempfehlung und Zulassungen werden Empfehlungen für die Anwendung der genannten Biologika im deutschen Gesundheitssystem gegeben. In einer gemeinsamen Anstrengung verschiedener Fachgesellschaften (AeDA, DGP, BdP, GAN, DGAKI, GPP, GPA) wurden Dokumentationsbögen für alle für schweres Asthma zugelassenen Biologika erstellt, die als Grundlage der Dokumentation dienen können. Es wurden hierbei sowohl Bögen für die Einleitung einer Biologikatherapie als auch Bögen zur Verlaufsdokumentation einer Biologikatherapie bei schwerem Asthma entwickelt. Die neuen Dokumentationsbögen fassen praxistauglich alle wichtigen Eckpunkte der Biologikaverordnung und der Beurteilung des Biologikaansprechens bei schwerem Asthma auf einer Seite zusammen und dienen sowohl der Sicherstellung einer leitliniengerechten und zulassungskonformen Verordnung als auch der Vermeidung von Arzneimittelregressen.

Biologics are the first-line treatment for patients with severe, inadequately controlled asthma. They can lead to a significant reduction in (or even complete avoidance of) exacerbations, a reduction in the need for systemic glucocorticoids with their many side effects, and a marked improvement in asthma control and lung function in severe asthma. Due to the high annual costs of biologic therapy, there is legitimate interest among health insurances in guideline- and approval-compliant as well as cost-effective use of biologics in severe asthma. On the other hand, there is also legitimate interest among treating physicians in prescribing these biologics without risk of insurer repayment demands. Using an analysis of the literature and regulatory approvals, the evidence for treatment with currently approved biologics for severe asthma—omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab, and depemokimab— was documented, and supplemented by the clinical experiences of the authors. Based on the guideline recommendations and approvals, recommendations are made for the use of the aforementioned biologics in the German healthcare system. In a joint effort by various professional associations (AeDA, DGP, BdP, GAN, DGAKI, GPP, GPA), documentation forms were created for all biologics approved for severe asthma, which can serve as a basis for documentation. Forms were developed both for the initiation of biologic therapy and for the documentation of biologic treatment responses in severe asthma. The new documentation forms concisely summarize all key points related to biologic prescription in severe asthma on a single page, serving both to ensure guideline-compliant and approval-compliant prescription and to avoid drug repayment demands.

Background:Biologics are the first-line treatment for patients with severe, poorly controlled asthma and can lead to a significant reduction (or even complete avoidance) of exacerbations and the need for systemic corticosteroids - which are associated with numerous side effects - as well as to a marked improvement in asthma control and lung function in severe asthma. Due to the high annual costs of biologic therapy, there is a legitimate interest on the part of payers in the cost-effective use of biologics for severe asthma in accordance with guidelines and regulatory approvals; conversely, there is a legitimate interest on the part of treating physicians in prescribing these biologics in a manner that protects them from liability claims. Methodology:In an analysis of the literature and regulatory approvals, combined with the experience of the participating authors, evidence was compiled regarding therapy with the biologics approved for severe asthma: omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab, and depemokimab. Results:Based on guideline recommendations and approvals, recommendations are provided for the use of the aforementioned biologics within the German healthcare system. In a joint effort by various professional societies (AeDA, DGP, BdP, GAN, DGAKI, GPP, GPA), documentation forms were created for all biologics approved for severe asthma, which can serve as a basis for documentation. Forms were developed both for initiating biologic therapy and for documenting the course of biologic therapy in severe asthma. Conclusion:The new documentation forms provide a practical, one-page summary of all key points regarding the prescription of biologics and the assessment of response to biologics in severe asthma, serving both to ensure prescribing in accordance with guidelines and regulatory requirements and to prevent drug-related claims.

Purpose:To collect prospective data from asthma patients treated with medium- (87/5/9µg) or high-strength (172/5/9µg) extrafine single-inhaler beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G, Trimbow®) in a real-world setting. Patients and Methods:TriMaximize is a non-interventional, prospective, multicenter study conducted in eight European countries (enrollment: 2021-2024). The primary objective was to describe patient characteristics and therapy pathways for adult patients with moderate to severe asthma treated with BDP/FF/G for up to 36 months. Assessments included demographic/clinical characteristics, pulmonary parameters, treatment pathways, asthma control measured by asthma control test (ACT), and health-related quality of life (HrQoL) measured by Mini Asthma Quality of Life Questionnaire (Mini-AQLQ). Results:In total, 1,445 patients (62.8% female; mean age: 57.6 years) were included. Before medium-strength BDP/FF/G initiation, 75.7% of the patients received a fixed ICS/LABA combination. Most patients starting with high-strength BDP/FF/G received fixed ICS/LABA (52.9%) or free ICS/LABA/LAMA (43.2%) combinations as prior therapy. Throughout the study, 87.1% of the patients remained on BDP/FF/G. At month 12, fewer patients (12.4%) used systemic corticosteroids (SCS) compared to baseline (33.2%). Use of rescue medication declined from 6.1 (baseline) to 3.6 puffs/week (month 12). During the first year, 79.5% of the patients experienced neither exacerbations nor used SCS. Three-component clinical remission was achieved in 45.6% (first year) and 59.3% (second/third year) of the patients. Four-component clinical remission was accomplished in 39.5% (first year) and 47.9% (second/third year). Improvements in asthma control (mean ACT change at month 12: 3.9; month 36: 4.8, p<0.0001) and HrQoL (mean Mini-AQLQ change at month 12: 0.8; month 36: 0.9, p<0.0001) exceeded the respective minimal clinically important differences. Forced expiratory volume in 1 second increased by 142 mL after 12 months (p<0.0001). Conclusion:Extrafine, single-inhaler BDP/FF/G therapy was effective and safe in a routine clinical practice setting in a multi-national cohort of patients with moderate to severe asthma.

Zusammenfassung Nationale und internationale fachärztliche Leitlinien sehen zu Recht die FeNO-Messung als unverzichtbares Element der Diagnostik und des effizienten Managements von Asthma an. Die Bestimmung von FeNO in der fachärztlichen Praxis führt zu einer verbesserten Versorgung von Patienten mit Asthma, durch (1) verbesserte Diagnostik von Asthma, (2) bessere Steuerung der inhalativen Therapie, (3) genauere Prüfung der Adhärenz und (4) präzisere Evaluation einer potentiellen Biologikatherapie. Eine regelmäßige Bestimmung des FeNO sollte daher essentieller Bestandteil der fachärztlichen Betreuung von Patienten mit Asthma in Deutschland sein. Ein verbessertes Asthma-Management durch FeNO-Messungen hat auch erhebliche gesundheitsökonomische Auswirkungen, durch Reduktion von direkten und indirekten Kosten. Eine Vergütung der FeNO-Messung über die gesetzlichen Krankenversicherungen (GKV) würde daher nicht nur zu einer besseren Versorgung von Asthma-Patienten, sondern auch zu einer Reduktion von Kosten in Deutschland führen.

Abstract:According to national and international asthma guidelines, FeNO measurement is an indispensable element in the diagnosis and efficient management of asthma. Testing FeNO in a specialist medical care leads to improved treatment of patients with asthma through (1) improved diagnosis of asthma, (2) better control of inhaled therapy, (3) more accurate assessment of adherence, and (4) more precise evaluation of potential biologic therapy. Regular FeNO measurement should therefore be an essential part of specialist care for asthma patients in Germany. Improved asthma management through FeNO measurement also has significant health economic implications as it reduces direct and indirect costs. Reimbursement of FeNO measurement by statutory health insurance (GKV) would therefore not only lead to better care for asthma patients, but also to a reduction in healthcare costs in Germany.

OBJECTIVE:Prospective real-world data on remission rates in patients with severe eosinophilic asthma (SEA) treated with benralizumab for more than 1 year are currently lacking. Here we investigate the long-term effectiveness of benralizumab treatment over 2 years on symptom control, clinical outcomes, and remission rates in real-world patients with SEA. METHODS:XALOC-2 is a prospective, observational real-world study in adults with SEA in Belgium, Canada, Germany, and Switzerland. Three-component clinical remission (3-CR; defined as the absence of exacerbations and oral corticosteroid use [over a 12-month period], and the presence of good asthma control [asthma control questionnaire (ACQ) thresholds of ≤0.75 or <1.5]), was assessed at Weeks 0/56/112. RESULTS:Among the 534 patients analyzed, median (interquartile range [IQR]) age at benralizumab treatment initiation was 58.0 (48.0-66.0) years; 76.3% had adult-onset asthma, and 49.3% were female. The median (IQR) ACQ score decreased from 3.0 (2.2-3.8) at baseline to 1.2 (0.6-2.3) at Week 56 and remained stable at Week 112 (1.2 [0.5-2.2]). When using the strictest ACQ threshold (≤0.75), the proportion of patients with 3-CR at Week 56 (27%) remained nearly unchanged at Week 122 (25%). A similar stability of 3-CR was observed when using the less strict ACQ threshold (<1.5): 42% at Week 56 and 41% at Week 112. CONCLUSIONS:Real-world patients with SEA showed early and sustained disease control and sustained remission rates after 2 years of benralizumab treatment. Even with the strictest ACQ threshold for asthma control, more than one-quarter of patients were in remission after 2 years of benralizumab.

The introduction of biologics, such as benralizumab (an anti-IL-5 receptor α humanised monoclonal antibody), has made remission a feasible goal for patients with severe eosinophilic asthma (SEA). However, there are remaining research gaps and no clear consensus on the definition of remission. We consolidated post hoc remission data from clinical trials and real-world studies of benralizumab in patients with SEA to gather insights on: testing different definitions; predictors of remission; the effect of comorbidities on achieving remission; remission and background medication reduction; long-term remission patterns with benralizumab; and remission in a real-life setting. In the SIROCCO and CALIMA Phase 3 randomised studies, patients with remission had higher baseline median blood eosinophil counts, were more likely to have a FEV1 of ≥ 65% predicted, had fewer exacerbations within 12 months and had lower mean ACQ-6 scores. Compared with the overall population, patients with a history of nasal polyps were also more likely to achieve remission with benralizumab. Analyses of the BORA and MELTEMI extension studies showed that in the longer term, once remission is achieved with benralizumab, patients are likely to remain in remission with continued treatment. In the open-label, single-arm ANDHI-In Practice and PONENTE studies, patients achieving remission had a shorter median time since asthma diagnosis, higher median age at asthma onset and lower median ACQ-6 scores. The SHAMAL study and the Phase 3b ANDHI-In Practice substudy demonstrate that remission is maintained with benralizumab even when patients reduce their background medication. Finally, the XALOC-1 real-world study highlights how patients with lower BMI are more likely to achieve remission with benralizumab. These findings demonstrate that achieving remission in patients with SEA is feasible with benralizumab and, in turn, inform future directions for research and treatment that includes a promising shift towards a new era of treat-to-target. This manuscript was supported by AstraZeneca, the manufacturer of benralizumab.

Rationale: ProVENT is an ongoing, multicenter, prospective, non-interventional observational study on dupilumab therapy for severe asthma in Germany, Austria, and Switzerland. Methods: 412 patients with severe asthma under dupilumab therapy have been included in the ProVENT study since February 2020. Currently, data before (399 patients), after 1 year (185 patients), and after 2 years of dupilumab therapy (100 patients) have been evaluated. Results: At baseline, median age of the patients was 56 years, with 3% aged ≤18 years; 53% women; 65% non-smokers. 60% of the patients had ≥1 type 2 comorbidity; and 84% had not received biologic therapy within the last 24 months. Fractional Exhaled Nitric Oxide (FeNO) and blood eosinophils were measured in 80% or 63% before and in 34% or 10% during dupilumab therapy, respectively. FeNO values normalized after the first visit (< 25 ppb) and remained stably low after 2 years. Over the 2-year period, there was a steady and sustainable improvement in asthma control (median decrease 5-item asthma control questionnaire [ACQ-5]: 2.6 to 0.9 points; median increase asthma control test [ACT]: 15 to 22 points) and quality of life (median increase Asthma Quality of Life Questionnaire [AQLQ]: 5.25 to 6.25 points). The improved lung function after 3 months (median forced expiratory volume in 1 second [FEV1]: 2.25 to 2.52 liters) stabilized over time (median FEV1 after 2 years: 2.51 liters). All patients had exacerbations in the last two years before therapy (median: 2). In contrast, after 1 and 2 years of dupilumab therapy, 89% of patients had no more exacerbations. Asthma remission (definition: no exacerbations or systemic steroid use; ACT ≥ 20 or ACQ ≤ 1.5; FEV1 ≥ 80% predicted or FEV1 decrease ≤ 5% of predicted value) was present in 56% of patients after 1 year, and in 58% after 2 years of treatment. Safety data corresponded to those in the approval studies. Conclusion: Dupilumab therapy leads to sustainable improvement in asthma control, quality of life, exacerbation rate, and lung function in patients with severe asthma in real-world practice. More than half of the patients are in asthma remission after 1 and 2 years of treatment. Type 2 biomarkers (especially blood eosinophils) are rarely measured in real-world practice during ongoing dupilumab therapy.

Oral corticosteroids (OCS) have been used for both maintenance and burst treatment of asthma since the 1950s owing to their beneficial effect on symptoms and exacerbations coupled with a historical lack of alternative therapies. Despite the current availability of well-tolerated and effective treatment with biologics, chronic OCS use remains high. This is of great concern because evidence suggests that a lifetime cumulative exposure even as low as 0.5 to 1.0 g prednisolone equivalent (about three to four bursts of OCS) significantly increases the risk of a wide range of acute and long-term adverse effects, some of which may not be fully reversible. Conversely, biologics have demonstrated a more favorable benefit-risk profile compared with OCS, while reducing exacerbations and improving symptom control. Here, we review the current situation, highlight the need for improved stewardship of OCS use, describe the cumulative and potentially irreversible toxicity seen with even short bursts of OCS, and discuss the role of biologics in minimizing their use. Finally, we provide our opinion on how maintenance OCS therapy in asthma can be relegated to history, with early patient risk evaluation to identify and measure biomarkers and/or clinical traits that may predict risk of future exacerbations, enabling proactive preventative intervention.