Oral Corticosteroid Dose Research Articles

Real-world mepolizumab treatment in eosinophilic granulomatosis with polyangiitis reduces disease burden in the United States.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, chronic inflammatory disease characterized by asthma and small/medium vessel vasculitis. Mepolizumab is approved for use in EGPA disease management alongside oral corticosteroids (OCS), but evidence of its real-world impact is limited. To compare real-world treatment patterns and health outcomes, particularly OCS use, EGPA-related hospitalizations/relapses, and asthma exacerbations pre- and post-mepolizumab initiation in US patients with EGPA. Patients with EGPA receiving ≥2 mepolizumab doses were identified using administrative claims data from Komodo Health's Comprehensive Dataset (December 2016-March 2020). Outcomes assessed pre- and post-mepolizumab initiation included corticosteroid/other medication use, EGPA-related hospitalizations/relapses, and asthma exacerbations. Overall, 114 patients were identified; of these, 60 (53%) received mepolizumab 300 mg at index. Average daily OCS dose per dispensing was significantly lower post- versus pre-mepolizumab initiation (21.2 vs 26.8 mg/day, 21% relative reduction, P<0.001); mean number of OCS bursts also decreased (0.9 vs 1.8, 50% relative reduction, P<0.001). Patients experienced significantly lower rates of EGPA-related hospitalization (0.86 vs 1.55 per person-year [PPY], 49% relative reduction, P=0.004) and EGPA relapse (3.18 vs 3.94 PPY, 19% relative reduction, P=0.004) post- versus pre-initiation. Most patients (91%) had an asthma diagnosis at baseline; among these patients, asthma exacerbation rates were significantly lower post- versus pre-initiation (1.05 vs 1.84 PPY, 42% relative reduction, P=0.004). Mepolizumab was associated with significant steroid-sparing benefits and significantly reduced rates of EGPA-related hospitalizations, EGPA relapses, and asthma exacerbations in this real-world study of US patients with EGPA, confirming the benefits of mepolizumab treatment seen in clinical trials.

Early treatment response to mepolizumab predicts clinical remission in severe eosinophilic asthma

Mepolizumab can induce an early response and clinical remission in people with severe eosinophilic asthma (SEA). We questioned whether early response to mepolizumab could predict future asthma remission, and sought to identify the best predictor of treatment response to mepolizumab for achieving remission. The Australian Mepolizumab Registry was used to investigate the early response to mepolizumab at 3 and 6 months and relate this to clinical remission at 12 months. Treatment response was assessed using the Asthma Control Questionnaire (ACQ)-5, oral corticosteroid (OCS) dose, exacerbation frequency, and post-bronchodilator FEV1. Clinical remission, assessed at 12 months, was defined as ACQ-5 ≤1.0 at 12 months, no exacerbations in the previous 6 months, and no OCS use for asthma in the previous 6 months. We estimated the optimism-corrected area under the curve (AUC) for internal validation. We analyzed 255 participants with SEA. Seventy-eight (30.6%) participants achieved clinical remission at 12 months. A prediction model including ACQ-5 score, exacerbation frequency, OCS dose, and post-bronchodilator FEV1 at 6 months was more predictive of achieving remission than measures at 3 months. ACQ-5 score at 6 months had the highest optimism-corrected AUC of 0.778 [95% CI: 0.719-0.833]. ACQ-5 score <1.5 at 6 months had a sensitivity of 85.9% for achieving clinical remission, while ACQ-5 score <0.75 had a specificity of 84.7%. ACQ-5 score at 6 months was the best predictor of achieving clinical remission at 12 months in people with SEA treated with mepolizumab. These results can be used to design a treat-to-target paradigm for asthma, where treatment response is assessed at 6 months to predict clinical remission.

Maintenance OCS Were Used More Frequently Than Biologics in Patients with Uncontrolled GINA 4/5 Asthma in Germany in 2019.

Asthma is affecting 4-5% of all adults (10% of children) in Germany, ≥ half are inadequately controlled. In 2019 up to 54 thousand patients suffered from severe uncontrolled asthma, 52% were treated/co-treated by pneumonologists. 45% of them had continuous oral corticosteroid (OCS)- and short-acting β2-agonist (SABA) overuse for ≥2 years. The aim of the current study was to analyze the main treatments, escalation schemes and the adherence to the GINA recommendations. Retrospective analysis in 2021 based on data from January to December 2019 in Germany, using the IQVIA™ LRx prescription database and the IQVIA™ Disease Analyzer database containing anonymized electronic medical records as the main data sources. In 2019 25,200 patients with severe, uncontrolled asthma treated in a pneumonologist´s practice in Germany received GINA 3 (0,4%), GINA 4 (76%) or GINA 5 therapy (24%) during the study year compared to 59% GINA 5 therapy in the 5-10% (1,500-3,000) co-treated in a specialized outpatient department. In Pneumonologists` practices the most frequent choice in GINA 5 was OCS in 69% of patients (biologicals 37%, long-acting muscarinic antagonist (LAMA) 20%) compared to 66% biologicals, 55% OCS, and 25% LAMA in the outpatient department. 54,958 of 613,000 GINA 4/5 patients were treated with OCS, 9,725 even with doses above the so called "Cushing threshold" for prednisolone of 2700 mg/year. After introduction of a biological treatment, patients reduced their SABA prescriptions by 28%, OCS by 55%, and OCS overall exposure by 40%, one-third did not need OCS anymore. In 75% of patients with uncontrolled asthma for ≥2 years therapy was not escalated beyond GINA 4 or low dose OCS was used as the most frequent add-on treatment in GINA 5 contradictory to treatment recommendations. Use of biologics reduced on demand rescue medication and OCS use.

Oral corticosteroid dosage and taper duration at onset in myelin oligodendrocyte glycoprotein antibody-associated disease influences time to first relapse

BackgroundWe sought to identify an optimal oral corticosteroid regimen at the onset of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), which would delay time to first relapse while minimising cumulative corticosteroid...

Efficacy and safety of benralizumab in eosinophilic granulomatosis with polyangiitis: A meta-analysis of eight studies.

Eosinophilic granulomatous polyangiitis (EGPA) is a rare autoimmune disease characterized by multisystemic inflammation, with eosinophils playing a central role in its pathogenesis. Traditional management relies heavily on corticosteroids and immunosuppressants, which are associated with significant side effects. The emergence of biologic agents, such as benralizumab, offers targeted therapeutic options by inhibiting the interleukin-5 receptor α, thereby reducing eosinophilic inflammation. This systematic review and meta-analysis comprehensively evaluate the efficacy and safety of benralizumab in EGPA patients, focusing on its ability to reduce oral corticosteroid (OCS) use, facilitate remission and spare immunosuppressants. We searched MEDLINE, LILACS and ISI Web of Science databases for relevant studies up to July 2024. Eight studies, including both randomized controlled trials (RCTs) and observational studies, were included in the meta-analysis, involving a total of 396 EGPA patients. The pooled analysis demonstrated a significant reduction in OCS dose, with an overall estimated effect of -8.25 mg/day (95% CI, -9.39 to -7.10). Complete remission was achieved in 56.8% of patients, and immunosuppressants were reduced or discontinued in 28.1% of cases. Adverse events (AEs) were reported in 21.9% of patients, with only one discontinuation due to an AE. These findings provide robust evidence supporting the use of benralizumab as an effective and well-tolerated treatment option for EGPA, significantly reducing OCS requirements and offering promising remission rates. Future research should focus on larger, multicentre RCTs to confirm these findings and further elucidate the long-term benefits and safety profile of benralizumab in EGPA.

Distinct trajectories of treatment response to mepolizumab toward remission in patients with severe eosinophilic asthma.

Patients with severe eosinophilic asthma, characterised by a high disease burden, benefit from mepolizumab, which improves symptoms and reduces exacerbations, potentially leading to clinical remission in a subgroup. This study aimed to identify treatment response trajectories to mepolizumab for severe eosinophilic asthma and to assess the achievement of clinical remission.Data from the Australian Mepolizumab Registry were used to assess treatment responses at 3, 6, and 12 months. The treatment response trajectories were identified using a group-based trajectory model. The proportions achieving clinical remission at 12 months, which was defined as well-controlled symptoms, no exacerbations, and no oral corticosteroid (OCS) use for asthma management, were compared between trajectories, and baseline predictors of the trajectories were identified using logistic regression analysis.We identified three trajectory groups: group 1, responsive asthma with less OCS use (n=170); group 2, responsive late-onset asthma (n=58); and group 3, obstructed and less responsive asthma (n=70). Groups 1 and 2 demonstrated higher proportions achieving clinical remission at 36.5% and 25.9%, respectively, compared to group 3 with 5.7% (p <0.001). Baseline predictors for assigned groups included lower OCS dose in group 1; greater FEV1% predicted, higher Asthma Quality of Life Questionnaire score, higher OCS dose, and nasal polyps in group 2; with group 3 as the reference.Treatment response to mepolizumab in severe eosinophilic asthma follows 3 trajectories with varying proportions achieving clinical remission and differing baseline characteristics. Treatment response variability may influence the achievement of clinical remission with mepolizumab therapy.

Ulcerative type 1 lepra reaction in borderline-tuberculoid leprosy

Introduction: leprosy is a chronic infectious disease caused by Mycobacterium leprae, characterized by a wide spectrum of clinical presentations. In India, borderline-tuberculoid leprosy is the most common form encountered in clinical practice. Type 1 lepra reaction in borderline- uberculoid leprosy usually presents as the development of erythema and/or edema in pre-existing skin lesions. Ulceration of skin lesions in type 1 lepra reaction is uncommon and occurs in severe reactions. Objective: to report an unusual presentation of borderline-tuberculoid leprosy with ulcerative type 1 lepra reaction in an immunocompetent patient. Case description: we present the case of a 65-yearold man with chief complaints of ulcerated plaque over his left thigh. He also had other skin lesions suggestive of borderline-tuberculoid leprosy over his trunk and limbs, as well asenlarged, mildly tender left ulnar and lateral popliteal nerves. A slit skin smear was negative, while a skin biopsy supported the diagnosis of borderline-tuberculoid leprosy. The patient responded to multibacillary multidrug therapy according recommended by World Health Organization and tapering doses of prednisolone, with complete healing of the ulceration at six weeks follow-up. Discussion: type 1 lepra reaction associated with borderline-tuberculoid leprosy usually presents with increased erythema and edema in pre-existing skin lesions. Ulceration in such skin lesions is not commonly seen except in cases with severe type 1 leprosy reactions. Administration of oral corticosteroids along with multibacillary multidrug therapy is the key to managing ulcerative type 1 lepra reaction. The ulceration heals rapidly with tapering doses of oral corticosteroids, limiting the duration of morbidity. Final consideration: the case emphasizes the need for dermatologists and leprologists to be aware of atypical presentations of leprosy reactions, ensuring timely diagnosis and effective management to achieve optimal patient outcomes.

Quantifying corticosteroid burden in chronic rhinosinusitis with nasal polyps: A retrospective US database study

BackgroundReal-world burden data on systemic corticosteroid (SCS) use in chronic rhinosinusitis with nasal polyps (CRSwNP) are limited. ObjectiveThis study's objective was to describe the real-world burden of SCS in CRSwNP. MethodsThis retrospective cohort study included commercial/Medicare Advantage with Part D health plan members from the Optum Research Database with a first medical claim (index) for CRSwNP (January 2015 to July 2020). Primary outcomes/variables included SCS use, healthcare resource utilization (HCRU) and costs during the 12-month follow-up period. Outcomes were analyzed overall (N=21,172) and stratified by baseline comorbid asthma status and sinus surgeries during follow-up. ResultsOverall, 64.7% and 41.0% of patients used all-cause and CRSwNP-related SCS respectively, and 36.0% had ≥1 oral corticosteroid (OCS) burst (≥20 mg for 3–28 days); SCS use was higher in patients with asthma and those with a NP-related surgery (1, 2, ≥3) versus without. The mean (SD) all-cause cumulative OCS dose was 303.3 (675.0) mg/year and 23.5% had a cumulative annual dose ≥400 mg; these values were higher (p<0.001) in patients with versus without comorbid asthma (514.9 [956.1] vs. 247.5 [567.0]; 36.9% vs. 19.9%). All-cause and CRSwNP HCRU and costs increased with increasing number of surgeries; mean (SD) all-cause total medical costs were $14,472 (38,915), $26,909 (40,800), $29,816 (41,677), and $31,558 (37,143) with 0, 1, 2, and ≥3 surgeries, respectively. ConclusionThese data highlight the significant burden of SCS use in CRSwNP, particularly in patients with comorbid asthma and suggest a need to reduce SCS exposure.

Rotation or change of biotherapy after TNF blocker treatment failure for axial spondyloarthritis: the ROC-SpA study, a randomised controlled study protocol

IntroductionAxial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate...

Polarization of circulating Follicular Helper T cells correlates with the severity of Bullous Pemphigoid.

T-follicular-helper (Tfh) cells form a distinct population of T-helper cells with different polarizations (type 1, type 2 and type 17) that regulates humoral responses and may participate in the pathophysiology of B-cell mediated autoimmune diseases, such as bullous pemphigoid (BP), a dermatosis mediated by auto-antibodies specific for hemidesmosomal proteins. The aim was to evaluate the impact of superpotent topical corticosteroid (TCS) treatment, which is more effective and safer than high doses of oral corticosteroids and recommended first-line treatment of BP, on circulating Tfh cells. We compared by flow cytometry the frequency, polarization and activation of blood Tfh cells from patients with BP at baseline and longitudinally after initiation of TCS treatment to age- and sex-matched healthy subjects. We observed that circulating Tfh cells were more frequent in patients with BP at baseline than in healthy subjects and exhibited an activated phenotype. We further showed a decrease of type 1 and an increase of type 17 Tfh cells in the blood of patients, which resulted in a higher (type 2+type 17) to type 1 Tfh cell ratio. This ratio correlated positively with disease severity as measured by the Bullous Pemphigoid Disease Area Index. Remarkably, along TCS treatment, although the frequency of Tfh cells returned to a level similar to control, the activated phenotype persisted. Interestingly serum IL-21 levels and the Tfh cell subset ratio, similarly to disease activity and serum anti-BP180 and anti-BP230 auto-antibodies, were decreased under the TCS treatment. Overall, our findings suggest an involvement of the polarization of Tfh cells in the pathophysiology of BP and open the door to a modulation of their activity for therapeutic purposes.

Prospective REALITI-A Study: 2-Year Real-World Benefits of Mepolizumab in Severe Asthma

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is of proven clinical benefit in severe asthma; prospective, long-term, real-world data in severe asthma are required. Research QuestionThis study aimed to assess the real-world benefit of 2 years’ mepolizumab treatment in severe asthma. Study Design and MethodsREALITI-A was a 2-year, international, prospective study enrolling adults with asthma, newly initiating mepolizumab 100 mg subcutaneously (physician decision). Outcomes in the 1-year pre-mepolizumab versus 2-year follow-up periods included rates of clinically significant asthma exacerbations (CSE; deterioration requiring systemic corticosteroids and/or emergency department [ED] visit/hospitalisation), exacerbations requiring ED visit/hospitalisation, exacerbations requiring hospitalisation, proportion of patients with no exacerbations, median daily maintenance oral corticosteroid (mOCS) dose, proportion of patients discontinuing mOCS completely, asthma control questionnaire (ACQ)-5 score, forced expiratory volume in 1s (FEV1) and adverse events (AEs). ResultsAfter 2 years’ follow-up, 73% of patients (n=599/822) had no record of mepolizumab discontinuation. During the 2-year follow-up versus pre-mepolizumab period (N=822), rates of CSEs, exacerbations requiring ED visit/hospitalisation, or hospitalisation only were reduced by 74%, 79% and 73%, respectively (odds ratio for no CSEs: 10.0; 95% confidence interval: 7.55, 13.25). Median (Q1, Q3) daily mOCS dose decreased from 10.0 (5.0, 14.7) mg at Week 0 (n=297) to 0.0 (0.0, 5.0) mg at Weeks 101–104 (n=168), and the proportion of patients discontinuing mOCS increased progressively to 43% at 1 year and 57% at 2 years. There was a 1.53-point reduction in ACQ-5 scores from baseline at 2 years. At Months 21–24, least square mean FEV1 improved by 142 mL from baseline. Ninety (11%) and 7 (<1%) patients experienced mepolizumab-related AEs and serious AEs during the follow-up period, respectively. InterpretationIn patients with severe asthma, real-world mepolizumab treatment for 2 years was well-tolerated, and was associated with sustained reductions in exacerbations and progressive reductions in mOCS use.

Real-World Effectiveness of Mepolizumab in Severe Asthma: Results from the Multi-country, Self-controlled Nucala Effectiveness Study (NEST).

The Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies. A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12months pre- and post-mepolizumab initiation. incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores). Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19-0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of -18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation. Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article.

Contemporary Concise Review 2023: Asthma.

Asthma research and management needs to meet the priorities of the end user-patients, carers and clinicians. A better understanding of the natural history of asthma and the progression of disease has highlighted the importance of early identification of patients with asthma and the potential role of early intervention. Management of mild asthma requires a consistent approach with the same detail and consideration used when managing severe disease. Evidence around treatable traits approaches continues to evolve, supporting the role of a personalized medicine in asthma. Oral corticosteroid (OCS) stewardship continues to be an urgent issue in asthma management. Strategies to taper OCS doses and the implementation of biologic therapies for their steroid sparing benefits will be important steps to address this problem. The concept of remission in asthma provides an ambitious target and treatment outcome.

Nodular posterior scleritis mimicking melanotic choroidal melanoma: A diagnostic dilemma.

To report a case of atypical nodular posterior scleritis mimicking as a melanotic choroidal melanoma. Descriptive case report. A 38-year-old female presented with sudden onset diminution of vision, severe pain and redness in her right eye. She was diagnosed to have choroidal melanoma in her left eye one year ago and underwent enucleation. On examination, conjunctiva was injected in right eye with cells in anterior vitreous face (AVF). Fundus examination revealed a large pigmented choroidal mass temporal to macula with exudative retinal detachment. Systemic evaluation and multimodal imaging ruled out the possibility of a choroidal melanoma or metastasis, with a presumptive diagnosis of nodular posterior scleritis. Three cycles of intravenous methyl prednisolone (IVMP) with a tapering dose of oral corticosteroids showed drastic improvement in symptoms with resolution of choroidal mass - further confirming the diagnosis. In cases of choroidal mass with an inflammatory component, a trial of steroids is worthwhile to prevent clinical misjudgement and devastating treatment outcomes including enucleation.

Real-world unified airway benefits of mepolizumab: Effectiveness in patients with asthma and comorbid nasal polyps

BackgroundNasal polyps (NPs) are commonly associated with chronic rhinosinusitis (CRS). In keeping with the unified airway hypothesis, asthma and CRS with NP (CRSwNP) frequently co-occur, share a similar pathophysiology, and are often treated with oral corticosteroids (OCS); however, a need for alternative treatment options for patients with comorbid asthma and CRSwNP remains. ObjectiveTo characterize the short- and long-term dual airway effectiveness of the anti–interleukin-5 monoclonal antibody, mepolizumab, in real-world patients with asthma and comorbid NP. MethodsAdult patients with CRSwNP who initiated mepolizumab from November 1, 2014, to September 30, 2021, were identified from 2 Merative MarketScan Research Databases. Outcomes were compared for the 12 months pre- and post-mepolizumab initiation and a variable follow-up period. Primary outcomes included the following: annual rate and proportion of patients with NP- and asthma-related exacerbations; NP surgery occurrences; all-cause OCS claims, number of OCS bursts, and daily OCS dose; all-cause and NP-related health care resource utilization. ResultsDuring the 12 months post-index, patients experienced fewer NP- and asthma-related exacerbations, required fewer sinus surgeries, and reduced use of OCS, with fewer all-cause OCS claims and OCS bursts. Significant reductions in asthma exacerbation-related and NP-related health care resource utilization were also observed. ConclusionThis study illustrated the near- and long-term real-world effectiveness of mepolizumab treatment, with a focus on dual lower and upper airway benefit from single-agent add-on therapy. These results may aid physicians in clinical decision-making for patients with asthma and comorbid CRSwNP with complex care needs.

The long-term outcomes of mepolizumab treatment at 100 mg dose on idiopathic chronic eosinophilic pneumonia: A real-life experience.

Background: The standard therapeutic regimen for idiopathic chronic eosinophilic pneumonia (ICEP) involves the administration of oral corticosteroids (OCS). However, a notable proportion of individuals experience recurrent episodes after the tapering or cessation of OCS during the course of ICEP. There has been a growing interest in exploring alternative treatment modalities for patients with ICEP at heightened risk of relapse. Objective: The aim of this study was to assess the efficacy of mepolizumab at a dose of 100 mg administered every 4 weeks in preventing relapses of ICEP and its impact on the clinical outcomes. Methods: This retrospective clinical observational study used real-world data to assess the impact of mepolizumab on patients diagnosed with ICEP accompanied by severe asthma. Demographic information and clinical characteristics were extracted from medical records. The study examined the effect of mepolizumab on the annual relapse rate, OCS dose, eosinophil count, and respiratory function parameters. Results: All patients included in the study, with a median (range) follow-up period of 19 months (4-40 months), the annual relapse rate decreased from 0.33 to 0 after the initiation mepolizumab. In addition, the maintenance OCS dose, expressed in methylprednisolone equivalents, declined from 4 mg/day to 0 mg/day. A reduction in the blood eosinophil count was observed, alongside a partial improvement in respiratory function test results among the patients. Conclusıon: A dose regimen of 100 mg of mepolizumab administered every 4 weeks emerges as a promising and well-tolerated therapeutic approach for averting relapses of ICEP.

Comparison of the Efficacy of Omalizumab and Mepolizumab in Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease

Introduction: Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is heterogeneous in both phenotypes and endotypes. Due to insufficient head-to-head comparison studies, it is hard to decide which biological to initiate. This study aimed to compare the efficacy of omalizumab and mepolizumab which can be used in the treatment of patients with severe eosinophilic asthma diagnosed with N-ERD. Methods: The population of this observational, cross-sectional study comprised of N-ERD patients who received omalizumab or mepolizumab for at least 6 months for severe asthma. Outcomes included the asthma control test (ACT), and sino-nasal outcome test scores (SNOT-22), blood eosinophil counts at initiation of biological treatment (T0, baseline) and at the end of 6th months (T6). Adverse effects related to biological treatment and changes of oral corticosteroids dose was recorded. Results: The study included a total of 22 patients, of whom 11 received mepolizumab and 11 received omalizumab. The change in ACT, SNOT-22, eosinophil counts, and adverse effects related to biologicals were similar at T6 (p = 0.606, p = 0.168, p = 0.05, p = 0.053, respectively). However, when examining the SNOT-22 and ACT based on the cumulative distribution curve (SUCRA), mepolizumab (SUCRA value: 0.61, 0.72, respectively) demonstrated greater efficacy compared to omalizumab (SUCRA value: 0.19, 0.35, respectively). The oral corticosteroids discontinuation rate was similar between the two groups (p = 0.05). Conclusion: We found both omalizumab and mepolizumab to be effective in treatment; however, we determined that mepolizumab may have a potential superiority in efficacy.

Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis

AbstractBackground and ObjectiveSeveral randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on‐treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on‐treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP).MethodsThroughout 2 years of treatment with benralizumab, a four‐component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function.ResultsThe present study recruited 164 patients suffering from SEA. After 24 months of add‐on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on‐treatment (exacerbation rate = 0, OCS dose = 0, pre‐bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT‐22 &lt; 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post‐bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on‐treatment (OR = 2.32, p &lt; 0.05 and OR = 5.59, p &lt; 0.01, respectively).ConclusionTaken together, the results of this real‐life clinical investigation indicate that benralizumab can induce a sustained remission on‐treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.image

Anti–IL-4R versus anti–IL-5/5R after anti–IL-5/5R failure in asthma: An emulated target trial

BackgroundSwitching biologics is now common practice in severe eosinophilic asthma. After insufficient response to anti-interleukin 5 or 5 receptor (anti-IL-5/5R), the optimal switch between an anti-IL-4R monoclonal antibody (mAb) (inter-class) or another anti-IL-5/5R drug (intra-class) remains unknown. ObjectiveWe compared the effectiveness of these two strategies on asthma control in patients with severe eosinophilic asthma and insufficient response to an anti-IL-5/5R mAb. MethodsWe emulated a target randomized trial using observational data from the RAMSES Cohort. Eligible patients were switched to an anti-IL-4R mAb or another anti-IL-5/5R drug after insufficient response to an anti-IL-5/5R mAb. The primary outcome was the change in Asthma Control Test (ACT) score at 6 months. ResultsAmong the 2046 patients in the cohort, 151 were included in the study: 103 switched to an anti-IL-4R mAb and 48 to another anti-IL-5/5R. At 6 months, the difference in ACT score improvement was not statistically significant (mean difference groups, 0.82 [-0.47,2.10], p=0.213). The inter-class group exhibited greater cumulative reduction in oral corticosteroids dose (Pinter-intra -1.05g [-1.76, -0.34], p=0.041). The inter-class group had a better effect, although not significantly, on reducing exacerbations (Δinter-intra -0.37 [-0.77, 0.02], p=0.124) and increasing lung function (FEV1) (126.8 ml [-12.7, 266.4], p=0.124). ConclusionAfter anti-IL-5/5R mAb insufficient response, switching to dupilumab demonstrated similar improvement in ACT scores compared to intra-class switching. However, it appeared more effective in reducing oral corticosteroid use. Larger studies are warranted to confirm these results.

Real-World Data on Tezepelumab in Patients With Severe Asthma in Germany

Tezepelumab is a novel biologic blocking thymic stromal lymphopoetin, approved for severe asthma irrespective of biomarker levels or phenotype. To characterize a real-world tezepelumab patient cohort and the efficacy among various asthma phenotypes. We performed a retrospective, multicenter study on patients with severe asthma initiating tezepelumab. Clinical response was evaluated at 3 and 6 months. We included 129 patients with an average age of 52.5 ± 13.1 years, 59.7% were female. The majority (86.0%) had increased type 2 (T2) biomarkers, 68.2% an allergic and 31.8% an eosinophilic phenotype. 23.3% of patients were biologic-naive. 22 (18.2%) patients discontinued tezepelumab therapy owing to suspected side effects or insufficient efficacy. At 6 months' follow-up, median reduction in annualized exacerbation rate was-1 [25th percentile; 75% percentile {-2.9; 0.0}], the reduction of oral corticosteroid dose among patients with long-term oral corticosteroid therapy was -5 mg [-10; 0] and the Asthma Control Test (ACT) improved by 2 [0; 5] points. A treatment response according to Biologic Asthma Response Score of 80.8% was demonstrated. There were no significant differences in treatment response between T2-high versus T2-low, early- versus adult-onset and eosinophilic versus non-eosinophilic asthma. Prior treatment with other biologics was associated with inferior treatment response. In this real-life cohort, including a large proportion of patients with history of previous biologic use and encompassing various subgroups, the majority responded to tezepelumab. Our data further suggest a steroid-sparing effect of tezepelumab.