Clinical Remission and Its Predictors After 12 Months of Biologic Therapy in Severe Asthma

Rationale: Achieving clinical remission (CR) in severe asthma is an emerging goal in asthma management, yet data on CR rates with biological therapies in Japan are limited. Benralizumab, an anti-IL-5 receptor alpha monoclonal antibody, has demonstrated efficacy in reducing asthma exacerbations and oral corticosteroid (OCS) use in patients with high blood eosinophil counts. However, the rate of CR achieved with benralizumab and its predictive markers in a Japanese population remain to be fully elucidated. Objective: This study aimed to evaluate the effectiveness of benralizumab in achieving CR in Japanese patients with severe asthma and to identify potential predictors of CR in this population. Methods: The Tokyo Asthma Study (TOAST: jRCTs031220079) was a multicenter, single-arm, interventional prospective study involving 97 patients with severe asthma. Eligible patients were 20 years or older, with blood eosinophil count ≥150 cells/μL, high adherence to inhaled corticosteroids (ICS), and a history of using additional long-term asthma control medications. Benralizumab was administered for 56 weeks, and CR was assessed using a combination of exacerbation rates, OCS discontinuation, symptom control (Asthma Control Questionnaire, ACQ-5), and lung function (FEV1). Peripheral blood counts were also analyzed to identify potential predictive markers for CR. Results: CR was achieved in 47% of patients when defined as no exacerbations, no maintenance OCS, and ACQ-5 <1.5. Additionally, 35% of patients achieved stricter CR criteria (ACQ-5 ≤0.75). When normalized lung function (FEV1 ≥80%) was included in the CR criteria, 31% and 23% achieved CR for ACQ-5 <1.5 and ≤0.75, respectively. Predictive markers associated with CR achievement included blood eosinophil count ≥438/μL (AUC 0.675, sensitivity 46.7%, specificity 74.5%), low neutrophil count ≤5,218/μL (AUC 0.609, sensitivity 87.0%, specificity 36.5%), and high platelet count ≥25.5 × 104/μL (AUC 0.616, sensitivity 48.6%, specificity 51.8%). Conclusion: Benralizumab was effective in achieving CR in approximately 30-40% of Japanese patients with severe asthma, with hematologic markers, including eosinophils, neutrophils, and platelets, indicating a higher likelihood of response.

<b>Objectives:</b> To correlate the cellular characteristics of T2-high inflammation in the bronchial biopsy with the clinical response to biological treatment among severe uncontrolled asthmatics. <b>Methods:</b> A multicentric prospective study that recruited severe uncontrolled asthma candidates for biological treatment. All participants were subjected to symptom control questionnaires (Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ)-6), exacerbations history, spirometry and fiberoptic bronchoscopy with bronchial biopsy for histopathological evaluation before the initiation of the biological therapy. Patients were re-evaluated after 6 months of treatment for clinical response (defined as ≤1 exacerbation and at least one of the following criteria:≥100ml improvement in FEV1 or ≥0.5 improvement points in ACQ-6 or ≥4 points in ACT). <b>Results:</b> 38 patients, 57.9% males, with a mean age of 52.7±13 years, and mean FEV1 66.7±16.5% were recruited. Asthma phenotypes were 5 allergic (12.8%), 17 eosinophilic (43.6%) and 16 allergic/eosinophilic (41%). 20 patients completed 6 months of biological therapy whereas 17 patients were responders (85%) with significant improvement in ACT (median of 14 (IQR=11–17) vs. 23 (IQR=20–25), p&lt;0.001), ACQ (p&lt;0.01), reduction of exacerbations (p&lt;0.001) and median FEV1 improvement of 380 ml (IQR=140–700). There was no significant correlation between eosinophil number in blood and bronchial biopsy (r=0.254,p=0.147). Eosinophils count in bronchial biopsy significantly correlated with FEV1% predicted after 6 months (r=0.741,p=0.006) <b>Conclusion:</b> Eosinophilia in bronchial biopsy could be a useful marker of response to biological therapy in severe uncontrolled asthma

Concurrent Blood Eosinophils and FeNO as Biological Therapy Indicators in Severe Asthma: Findings From the Precision Medicine Intervention in Severe Asthma Study.

Positioning Infliximab and Vedolizumab in the Treatment of Moderate-to-Severe Ulcerative Colitis

Background: To achieve clinical remission (CR), optimal selection of biologics is critical for maximizing therapeutic response in patients with severe asthma. However, few reports have comprehensively examined factors associated with CR during treatment with different biologics. This real-world study examined the rates of CR in patients with severe asthma receiving anti-IL-4Rα, anti-IL-5/5R, or anti-IgE treatment, then explored baseline clinical factors associated with CR after biologic treatment.Methods: In this Japanese multicenter retrospective observational study, we consecutively included patients with severe asthma whose spirometry and asthma control test (ACT) data were available to determine CR after at least 1 year of either anti-IL-4Rα, anti-IL-5/5R, or anti-IgE treatment. The 3-domain CR was defined as fulfilling all conditions, including no maintenance oral corticosteroid (OCS) use, no exacerbation in the previous year, and ACT ≥ 23. The 4-domain CR was defined as fulfilling no OCS, no exacerbation, ACT ≥ 20, and percentage predicted forced expiratory volume in 1 sec ≥ 80%. Baseline clinical factors were compared between patients with and without CR after each biologic treatment.Result: A total of 236 patients with severe asthma were included (N=81, 104, 51 for anti- anti-IL-4Rα, anti-IL-5/5R, anti-IgE treatment group, respectively). The 3-domain CR and 4-domain CR were found in 38 (47%) and 29 (36%) patients receiving anti-IL-4Rα treatment, 33 (32%) and 23 (22%) patients receiving anti-IL-5/5R treatment, and 14 (28%) and 11 (22%) patients receiving anti-IgE treatment. In the anti-IL-4Rα group, FeNO levels and the prevalence of chronic rhinosinusitis were significantly higher in patients with 3-domain CR than those without. In the anti-IL5/5R group, FeNO was significantly higher in those with 3-domain CR than those without. In multivariate models, the presence of rhinosinusitis and higher FeNO levels were associated with the 3-domain CR in patients receiving anti-IL-4Rα treatment, but not anti-IL-5/5R treatment, after adjusting for baseline OCS use, past-year exacerbations history, body mass index, sex, and disease duration. Moreover, higher FeNO levels were associated with the 4-domain CR in patients receiving anti-IL-4Rα treatment after adjustment for the same variables. Conclusion: The rates of 3-domain CR and 4-domain were 28-47% and 22-36%. Anti-IL-4Rα treatment may be effective for patients with severe asthma who have chronic rhinosinusitis and higher FeNO levels at baseline examination.

Tezepelumab is an anti-TSLP monoclonal antibody approved for the treatment of severe asthma. It has broad downstream anti-T2 effects, offering the prospect of biological remission. Real-world data on clinical remission rates with tezepelumab is lacking, and the relationship between clinical and biological remission is unclear. Finally, the effectiveness of tezepelumab in patients who have failed to respond to existing biologic therapies is unknown. Clinical and biomarker data from adults with severe asthma treated with tezepelumab in a real-world setting was analyzed. Clinical outcome measures including clinical remission were recorded along with rates of biological remission (defined as blood eosinophil count < 300 cells/mcL and FeNO < 25 ppb). One hundred seventy-five patients were included. 98/175 (56%) had switched from another biologic. Following tezepelumab initiation, the exacerbation rate decreased from 3.1 (2.5) to 0.8 (1.4), with 59% of patients remaining exacerbation-free at 1 year. 54% achieved an ACQ score < 1.5. Clinical remission at 1 year was observed in 36%, with a rate of 55% in T2-high patients versus 19% in T2 low patients. The clinical response in biologic-naïve and biologic switch patients was similar. FeNO declined from 41 ppb (24-76) to 24 ppb (16-38) and BEC fell from 300 cells/μL (60-610) to 180 cells/μL (105-320) (both p < 0.001). 38% achieved biological remission. 15% attained both clinical and biological remission. Tezepelumab led to substantial clinical improvements and clinical remission in up to 55% of T2-high patients with severe asthma. A disconnect between clinical and biological remission was observed. The long-term significance of residual T2 inflammation on tezepelumab is unknown.

Mucus Plug Score Predicts Clinical and Pulmonary Function Response to Biologic Therapy in Patients With Severe Asthma.

Background and Objectives: Asthma is a complex disease marked by chronic respiratory symptoms and inflammation. Recent advances in biologic therapies have improved symptom control in patients with severe asthma, raising interest in achieving clinical remission. This study aimed to evaluate the prevalence of clinical remission in severe asthma patients treated with biologics and identify factors associated with achieving remission. Methods: The study recruited 116 patients from a national severe asthma registry in Kuwait, focusing on patients who had been treated with biologic (omalizumab, mepolizumab, benralizumab and dupilumab) therapy for at least 12 months. Clinical remission was defined as the absence of exacerbations, no use of oral corticosteroids (OCS), an Asthma Control Test (ACT) score of ≥ 20, Asthma Control Questionnaire (ACQ-6) score of &amp;lt; 0.75 and forced expiratory volume in one second (FEV1) ≥80% predicted. Data were collected on demographic, clinical, and functional parameters, including biomarkers such as blood eosinophil count (BEC), total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO), as well as the polymorphism patterns of the interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) genes. Results: Patients with severe asthma were predominantly female (68.9%) with an average age of 54.09 years. Most had adult-onset asthma (67.3%), comorbid allergic rhinitis (81.03%), and experienced frequent exacerbations, with a median of four corticosteroid-requiring flare-ups per year. The allergic eosinophilic phenotype was common (74.14%), and a significant portion carried the CC genotype of the IL-4 gene (51.72%) or the GG genotype of the TNFα gene (57.76%). Biological therapy significantly improved asthma control, reducing exacerbations and oral corticosteroid use while improving lung function (p=0.001 for all). About 18.1% of patients achieved clinical remission after at least 12 months of biologic therapy, with dupilumab being the most effective, especially in treatment-naive patients. A multiple logistic regression analysis found that increasing age was negatively associated with remission (OR 0.95, p=0.02), while the CC genotype of the IL-4 gene (OR 4.57, p=0.008) and the use of dupilumab (OR 3.63, p=0.001) were strong positive predictors of clinical remission. Conclusion: This study suggested that clinical remission can be achieved in adorable portion of patients with severe asthma. However, biologic therapy, particularly dupilumab, offers a promising avenue for achieving disease remission rather than other biological treatment especially in younger patients with specific genetic profiles (CC genotype of the IL-4 gene)

Background and objectivesAsthma is a complex condition characterized by variable respiratory symptoms and chronic inflammation. In recent years, the use of biologics in severe asthma patients led to significant improvements in symptom control and disease outcomes. This has prompted healthcare providers to explore the possibility of achieving clinical remission (CR). This study aimed to evaluate the prevalence of clinical remission in severe asthma patients treated with biologics. Additionally, to identify factors associated with achieving clinical remission.MethodsThe study recruited 116 patients from a national severe asthma registry in Kuwait, focusing on patients who had been treated with biologic therapy for at least 12 months. CR was defined as the absence of exacerbations and oral corticosteroids (OCS) use, an Asthma Control Test (ACT) score of ≥ 20, Asthma Control Questionnaire (ACQ-6) score of ≤ 0.75 and forced expiratory volume in one second (FEV1) ≥ 80% predicted. Data were collected on demographics, clinical, and functional parameters; including biomarkers such as blood eosinophils count (BEC), total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO), as well as the polymorphism patterns of the interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) genes.ResultsPatients with severe asthma were predominantly female (68.9%) with an average age of 54.09 years. Most had adult-onset asthma (67.3%), comorbid allergic rhinitis (AR) (81.03%), and experienced frequent exacerbations, with a median of four corticosteroids-requiring flare-ups per year. The allergic eosinophilic phenotype was common (74.14%), and a significant portion carried the CC genotype of the IL-4 gene (51.72%) or the GG genotype of the TNFα gene (57.76%). Biologic therapy significantly improved asthma control, reduced exacerbations and OCS use while improved lung function (p = 0.001 for all). About 18.1% of patients achieved CR after at least 12 months of biologic therapy, with dupilumab being the most effective, especially in biologic-naive patients. A multiple logistic regression analysis found that increasing age was negatively associated with CR (OR 0.95, p = 0.02), while the CC genotype of the IL-4 gene (OR 4.57, p = 0.008) and the use of dupilumab (OR 3.63, p = 0.001) were strong positive predictors of CR.ConclusionThis study suggested that CR can be achieved in patients with severe asthma. However, biologic therapy, particularly dupilumab, offers a promising avenue for achieving CR in comparison to other biologics, especially in younger patients with specific genetic profiles (CC genotype of the IL-4 gene).

To investigate the rate of subclinical inflammation in patients with axial spondyloarthritis (axSpA) with nonsteroidal anti-inflammatory drug (NSAID)/anti-tumor necrosis factor (TNF)-α drug-induced clinical remission and to explore factors influencing clinical and imaging remission. One hundred twenty-five patients with axSpA followed up for at least 6months were enrolled in this prospective study and randomly divided into two groups. Ninety patients were treated with anti-tumor necrosis factor (TNF)-α or anti-TNF-α combined with nonsteroidal anti-inflammatory drugs (NSAIDs) (anti-TNF-α treatment group), and thirty-five patients were treated with only NSAIDs (non anti-TNF-α treatment group). The improvements in the clinical remission rate, imaging remission rate, and disease parameters before and after the different treatments were compared. Risk factors for clinical and imaging remission were analyzed by multivariate logistic regression analysis. The clinical and imaging remission rate was increased after treatment especially in the anti-TNF-α group (P < 0.001). The remission rate of imaging in the group with clinical remission was higher than that in the group with clinical non-remission (P < 0.05). After treatment, the remission rates of imaging in the clinical remission and non-remission group were significantly higher than those before treatment (P < 0.0001). The results of multivariate logistic regression analysis showed that higher CRP was a risk factor for failure of clinical remission in axSpA (OR = 2.034, 95% CI:1.595 ~ 2.617, P < 0.001), while higher ASDAScrp was a risk factor for failure of imaging remission (OR = 1.306, 95% CI:1.026 ~ 1.688, P < 0.05). Anti-TNF-α treatment was a protective factor for both clinical (OR = 0.234, 95% CI:0.091 ~ 0.605, P < 0.05) and imaging remission (OR = 0.511, 95% CI:0.286 ~ 0.914, P < 0.05). Even after regular treatment, some clinical remission patients continued to have evidence of subclinical inflammation. Higher CRP and ASDAScrp are risk factors for clinical and imaging non-remission in axSpA respectively, Continuous NSAID treatment (more than 1year) can effectively improve clinical and MRI inflammation in patients, but anti-TNF-α treatment is more beneficial for clinical and imaging remission. Key Points • Some patients achieving ASDAScrp remission status continue to have inflammation when assessed with objective imaging techniques. • MRI can sensitively measure bone marrow inflammation and may provide a more accurate assessment of remission. • Controlling inflammation, especially reducing CRP and ASDAScrp levels, is a key factor for achieving clinical and imaging remission in patients with axSpA.

Background Clinical remission has recently been proposed as a possible treatment goal even in severe asthma. In this real-world study, we aimed to assess the achievement rate and predictive factors of clinical remission using omalizumab in patients with severe asthma. Methods This retrospective observational study included patients with severe asthma initiated with omalizumab therapy and recruited from the asthma clinic of the Akdeniz University Hospital, Turkey. Clinical remission was defined as patients who received no oral corticosteroid (OCS) therapy; showed no exacerbations; showed an asthma control questionnaire score of ≤ 1, asthma control test (ACT) of ≥ 20, or both and, FEV1 of ≥ 80% predicted. Results A total of 58 patients were included in the study, with an average age of 56.4 ± 13.6 years. The mean duration of asthma was 23.5 ± 11.8 years and the mean duration of omalizumab treatment was 80.05 ± 35.04 months. Clinical remission rates were 25.9% in the first and second year, 34.0% in the third year, 34.1% in the fourth year and 47.4% in the fifth year. Pre-omalizumab ACT, FEV1 (%) and OCS use were significantly higher in patients with clinical remission at 1 year. Logistic regression analyses showed that none of the factors predicted clinical remission. Conclusion Omalizumab has the potential to induce disease remission in a significant proportion of people with severe asthma, and this is maintained and improved over time.

Background: Dupilumab, a monoclonal antibody targeting the IL-4/IL-13 receptor, has shown significant efficacy in improving asthma control and reducing exacerbations in patients with severe eosinophilic asthma. However, there is a lack of knowledge about real-world data on clinical remission rates and their predictors. Objective: This study aimed to evaluate clinical outcomes, remission rates, and predictive factors of remission in a real-life cohort of patients with severe eosinophilic asthma treated with dupilumab. Methods: We conducted a retrospective, bicentric, observational study including 52 patients with severe eosinophilic asthma treated with dupilumab. Clinical, functional, and biomarkers were assessed at baseline, 6 months, and 12 months. Statistical analyses included logistic regression to identify independent predictors of clinical remission. Results: After 12 months of treatment, 48.2% of patients achieved clinical remission. Dupilumab significantly improved asthma control and lung function (including FVC and FEF25-75), reduced exacerbation rates, and maintenance therapy. High blood eosinophil levels (>490 cells/µL), high FeNO levels (>25 ppb), a history of CRSwNP, and better baseline FEV1 were associated with asthma remission. Conversely, obesity (BMI > 30) and related comorbidities (such as GERD, OSAS, and hypertension) and bronchiectasis were associated with a lower likelihood of remission. Multivariate analysis confirmed higher baseline FEV1 (OR 2.94; IC 1.13-7.6), positive history of CRSwNP (OR 8.03; IC 1.41-45.5), and higher baseline blood eosinophils (OR 1.003 IC 1.001-1.006) as independent predictors of clinical remission. Conclusions: These results are in line with the known effectiveness of dupilumab in severe eosinophilic asthma and identified a history of CRSwNP, higher baseline FEV1, and elevated blood eosinophils as key predictors of clinical remission. These findings may contribute to a more personalized approach to treatment selection, emphasizing the importance of comorbidity assessment together with type 2 inflammation biomarkers. Further prospective studies are needed to validate these results.

Background/Objectives: In recent years, the concept of clinical remission under treatment in asthma has gained increasing attention. It is defined as the absence of exacerbations, asthma symptoms, and oral corticosteroid use for at least 12 months, together with improved or stable lung function. This study aimed to evaluate the clinical remission rates and associated factors in patients with severe asthma receiving biologic therapy with either omalizumab (anti-IgE) or mepolizumab (anti-IL-5). Methods: Adult patients with severe asthma and type 2 inflammation who started omalizumab or mepolizumab between January 2009 and December 2023 in our allergy clinic were retrospectively analyzed. Sociodemographic and clinical characteristics were reviewed. Clinical remission rates were assessed at the first and most recent years of maintenance therapy. Independent markers were identified using multivariable analyses. Results: A total of 160 patients were included (mean age 53.8 ± 14.6 years; 81.9% female). Of these, 85.6% received omalizumab and 14.4% mepolizumab. Remission rates at one year and at the latest follow-up were 60.0% and 43.7%, respectively. Patients achieving remission had higher total IgE levels. Psychiatric comorbidity negatively affected remission. The one-year remission rates were 91.3% in the mepolizumab group and 54.7% in the omalizumab group. Higher baseline blood eosinophil counts and Asthma Control Test (ACT) scores were positive markers, while psychiatric disease was inversely associated. Conclusions: Omalizumab and mepolizumab achieved meaningful clinical remission rates in severe asthma. Elevated ACT scores and eosinophil counts and absence of psychiatric comorbidities were independent markers, underscoring the need for individualized biologic therapy to achieve sustained remission.

Exploring factors associated with clinical remission in patients with severe asthma receiving anti-IL-4Rα, anti-IL-5/5R, or anti-IgE treatment.

IntroductionClinical remission as a multicomponent treatment goal in severe asthma is being explored in clinical practice. This post hoc analysis used data from the REDES study to assess the proportion of patients with severe eosinophilic asthma achieving our multicomponent definitions of clinical remission after 1 year of mepolizumab treatment.MethodsThe real-world, retrospective observational REDES study enrolled patients with severe eosinophilic asthma who were newly prescribed mepolizumab and with ≥12 months of medical records pre-enrolment. Multicomponent clinical remission was defined as: oral corticosteroid (OCS)-free; exacerbation-free; asthma control test (ACT) score ≥20; and with or without post-bronchodilator forced expiratory volume in 1 second ≥80%. Baseline characteristics were also assessed in those who did/did not achieve clinical remission.Results37% and 30% of patients with severe eosinophilic asthma met our proposed three- and four-component on-treatment clinical remission definitions; an increase from 2% and 3% at baseline. Most frequently achieved individual components of clinical remission were: OCS-free; ACT score ≥20. For patients fulfilling the multicomponent clinical remission definitions, at baseline we observed higher blood eosinophil counts, better ACT scores and lung function, lower maintenance OCS use, and a slightly lower rate of prior exacerbations versus those who did not.DiscussionClinical remission is a realistic target in clinical practice for a subset of patients with severe eosinophilic asthma receiving mepolizumab. Further studies are required to elucidate whether features linked to the underlying endotype can help predict treatment outcomes, increase rates of clinical remission, and potentially modify disease progression.