Global variability in administrative approval prescription criteria for biologic therapy in severe asthma

Background Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine. Objective To compare global differences in ease of access to biologics. Methods In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access. Results Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti–IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower. Conclusions Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world

Predictors of response to therapy with omalizumab in patients with severe allergic asthma–a real life study

Objectives: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab. Methods: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician’s global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders. Results: Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV1 and FEV1/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV1 (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709). Conclusion: Lower baseline FEV1 and higher IL-13 levels in induced sputum supernatant were predictors of response to omalizumab. Patients with higher baseline serum IgE levels, shorter disease duration and higher blood eosinophils may experience a late response and might benefit from a more prolonged treatment before being characterized as non-responders. © 2017 Informa UK Limited, trading as Taylor & Francis Group

Vedolizumab-induced acute interstitial lung injury in a 39-year-old male with ulcerative colitis

Vedolizumab, an anti-integrin antibody, is effective for moderate to severe ulcerative colitis and Crohn's disease treatment with a good safety profile due to its gut selective mechanism of action. Upper respiratory tract vedolizumab adverse events are common; however, they are mild and do not require treatment withdrawal. Herein, we present a 39-year-old patient under vedolizumab treatment for ulcerative colitis who presented acute severe interstitial lung injury that necessitated vedolizumab withdrawal and systemic steroids administration. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved

Mycophenolate mofetil as an alternative treatment in sarcoidosis

Introduction: In sarcoidosis although no better drug therapy than corticosteroids (CS) has emerged, alternative immunosuppressive agents are used when indicated. Mycophenolate mofetil (MMF) presents rapid action, a considerable safety profile and absence of lung toxicity. Few data exist so far on its use in patients with sarcoidosis. This is a retrospective study on the effectiveness and safety of MMF in patients with sarcoidosis. Materials and methods: All patients with biopsy proven sarcoidosis treated for at least 1 year with MMF from 2008 to 2017 in our department are evaluated. Results: Eight patients with both pulmonary and extrapulmonary disease are included in the analysis. During follow-up, symptoms and chest radiological findings improved in all. A statistically significant improvement of FEV1 and FVC is reported (p = 0.010 and p = 0.021 respectively). Cardiac and renal disease resolved during treatment while dermal disease significantly improved. MMF permitted CS dose reduction from 15.0 (10.0, 35.0) to 2.5 (0.0, 5.0) mg prednisolone (or equivalent), p = 0.016. All patients but one, tolerated well MMF. Conclusion: MMF as an alternative drug in systemic sarcoidosis, proved safe and effective, permitting the reduction of the dose of oral CS and leading to clinical, functional and radiological improvement. © 2019 Elsevier Lt

Prevalence, distribution and clinical significance of joints, muscles and bones in sarcoidosis: an 18F-FDG-PET/CT study

Objectives: In Sarcoidosis joints-muscles-bones (JMBs) localizations are of the least common. 18F-FDG-PET/CT imaging revolutionized detection of JMBs involvement by adding metabolic activity information and allowing for a comprehensive, whole-body mapping of the disease. Aim and methods: This study investigated prevalence, distribution, and clinical significance of JMBs sarcoidosis in 195 consecutive patients that underwent 18F-FDG PET/CT examination. Results: Joint and bone involvement were encountered in 15% of patients with a mean of the maximum-standardized-uptake-value (SUVmax) of 6.1. Most common location was the axial skeleton. Hypercalciuria was significantly more frequent in patients with osseous involvement (p = 0.003). Muscle activity (SUVmax = 2.4) was encountered in 20% of the patients, most frequently in treatment-naïve (p = 0.02). The muscles of the lower extremities were affected the most. Muscle and bone localization coexist in 50% of the cases. JMBs disease was almost asymptomatic, not related to chronicity but to pulmonary, nodal, and systemic disease. Long-term follow-up and treatment response of affected patients confirmed sarcoidosis. Conclusion: 18F-FDG-PET/CT revealed JMBs localizations and coexistence with other organ sites supporting the concept that sarcoidosis is a systemic disease. By allowing an integrative interpretation of multi-organ involvement in the context of a pattern highly suggestive of sarcoidosis, it strongly keeps-off the diagnosis of malignancy. © 2020 Informa UK Limited, trading as Taylor & Francis Group

Mepolizumab in Severe Eosinophilic Asthma: A 2-Year Follow-Up in Specialized Asthma Clinics in Greece: An Interim Analysis

Mepolizumab is a monoclonal antibody against IL-5 for the treatment of severe eosinophilic asthma. The aim of the current study was to present a predesigned interim analysis of the data of patients who have completed 1 year of therapy with mepolizumab. Methods: This study is a prospective multicenter, noninterventional 2-year observational study and aims to describe the clinical benefit and safety profile of mepolizumab in patients with severe eosinophilic asthma. Results: Compared to the year preceding the initiation of treatment, the annual rate of exacerbations decreased significantly, from 4.3 ± 2.3 to 1.3 ± 1.8; p < 0.0001. Forty-two patients received maintenance dose of oral corticosteroids (OCS) at baseline. From these patients at the end of 1 year of therapy with mepolizumab, 17 patients (40%) had achieved OCS discontinuation. A reduction in the median dose of OCS was also achieved. After 1 year of treatment with mepolizumab, the asthma control test score significantly increased from 16.3 ± 3.7 to 21.2 ± 3.8 (p < 0.0001). This marked clinical improvement was paralleled by a significant reduction of blood eosinophil count. All patients showed a considerable improvement of airflow limitation. In respect to adverse events of treatment with mepolizumab, 19 patients (27%) were recorded to have at least one such occurrence during their 1-year treatment. Conclusions: We have shown that in patients with severe eosinophilic asthma, 1 year of treatment with mepolizumab was safe, resulted in significant reduction of the annual exacerbation rate, reduction (or even discontinuation) of the needed dose of OCS, and improvements of asthma control and lung function. © 202

Autoimmune pulmonary alveolar proteinosis in children

In childhood, a multitude of causes lead to pulmonary alveolar proteinosis (PAP), an excessive surfactant accumulation in the alveolar space, limiting gas exchange. Autoantibodies against granulocyte–macrophage colony-stimulating factor (GM-CSF) causing autoimmune PAP, the principal aetiology in adults, are rare. In this first case series on autoimmune PAP, we detail the presentation and management issues of four children. Whereas three children presented insidiously with progressive dyspnoea, one was acutely sick with suspected pneumonia. During management, one patient was hospitalised with coronavirus disease 2019, noninvasively ventilated, and recovered. All treatment modalities known from adults including whole-lung lavage, augmentation of GM-CSF by inhaled GM-CSF, removal of neutralising antibody by plasmapheresis and interruption of antibody production using rituximab were considered; however, not all options were available at all sites. Inhaled GM-CSF appeared to be a noninvasive and comfortable therapeutic approach. The management with best benefit-to-harm ratio in autoimmune PAP is unknown and specialised physicians must select the least invasive and most effective treatment. To collect this cohort in a rare condition became feasible as patients were submitted to an appropriate registry. To accelerate the authorisation of novel treatments for autoimmune PAP, competent authorities should grant an inclusion of adolescents into trials in adults. © The authors 2022