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Pulmonary – Treatable traits
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
The targets for biological agents are shown in Figure 2.7 and their clinical effects and effects on biomarkers are summarised in Table 2.6. Monoclonal antibodies inhibiting the effect of IL-5 (Mepolizumab, Reslizumab and Benralizumab), IL-4 and IL-13 (Dupilumab, which inhibits both cytokines by targeting the common IL-4 receptor alpha), TSLP (Tezepelumab) and IgE (Omalizumab) are available for use in patients with severe asthma who continue to have asthma attacks despite optimum inhaled treatment with inhaled corticosteroids and LABA. Their effects are greater in subgroups identified using biomarkers and to a large extent, the most predictive biomarker is that most closely associated with the cytokine that is being blocked (i.e. blood eosinophils for anti-IL-5 and FeNO for anti-IL-4/13).
The Pharmacotherapy of Rhinitis and Asthma
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Amanda Grippen Goddard, Harold S. Nelson, Rohit Katial, Flavia Hoyte
Since most of the Th2-low patients have a poor response to oral steroids, other pharmacologic therapies have shown promise in reducing exacerbations and improving symptoms. Azithromycin used as add-on therapy in patients with uncontrolled, persistent asthma on medium-to-high ICS plus LABA has shown significant reductions in asthma exacerbations and improved asthma-related quality of life compared to a placebo (Gibson et al. 2017). Tiotropium and bronchial thermoplasty can provide benefit for asthma patients, regardless of the type of inflammation driving their disease. Other interventions targeting non-type-2 inflammation in asthma including IL-17 and CXCR2 have been disappointing in clinical trials (Busse et al. 2013, O’Byrne et al. 2016). IL-6 and CRP have been shown to be elevated in Th2-low asthmatics, particularly those with obesity. There have been promising reductions in neutrophil recruiting cytokines/chemokines and allergen-induced airway inflammation in mice using antibody-mediated neutralization of IL-6 (Chu et al. 2015). Tezepelumab (anti-TSLP monoclonal antibody) has shown, small but significant exacerbation reduction in patients with low FeNO in phase 2 clinical trials suggesting it may be beneficial in Th2-low inflammation patients (Corren et al. 2017).
Bronchus-associated lymphoid tissue and immune-mediated respiratory diseases
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Dale T. Umetsu, Bart Lambrecht
Tezepelumab/AMG157 (Amgen) has been shown to reduce airway changes following allergen challenge in patients with mild to moderate asthma, suggesting an important role for TSLP in asthma. Tezepelumab is currently being studied in patients with asthma and with atopic dermatitis.
Cost-effectiveness of tezepelumab in Canada for severe asthma
Published in Journal of Medical Economics, 2023
Mara Habash, Hannah Guiang, Irvin Mayers, Anna Quinton, Vivian Vuong, Aidan Dineen, Sumeet Singh, Danny Gibson, Adrian P. Turner
Although severe asthma affects a minority of the population with asthma, it is associated with disproportionate humanistic and economic burden, accounting for 50% of total asthma direct costs2. Currently available biologics in Canada for severe asthma target specific phenotypes, potentially leaving other pathways of airway inflammation wholly unaddressed. Eligibility for current biologics is dependent on biomarker profile; however, studies have demonstrated that approximately half of patients with severe asthma have been shown to change phenotypes in one year6. Furthermore, up to 49% of severe asthma patients exhibit multiple drivers of inflammation4,61,62. In addition, there are no biologics indicated for patients with severe, non-allergic, non- EOS asthma. Hence, there remains significant unmet need for patients with severe asthma. Tezepelumab has been demonstrated to be an effective treatment that reduces exacerbations and provides effective asthma control across inflammatory phenotypes, regardless of biomarker status, and will help address these unmet needs that remain in severe asthma.
An overview of the preclinical discovery and development of tezepelumab for the treatment of asthma
Published in Expert Opinion on Drug Discovery, 2023
Maria Gabriella Matera, Josuel Ora, Paola Rogliani, Mario Cazzola
The critical role of TSLP, which is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses, and other airborne particles, prompted the development of tezepelumab, which is a mAb capable of blocking TSLP at the top of the inflammation cascade, thereby preventing the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved disease control. An extensive clinical development program has shown that tezepelumab can improve all key primary and secondary endpoints in patients with severe asthma, compared to placebo, when added to standard therapy. Of particular importance is the favorable impact of this biological drug on exacerbation rates and lung function in patients with uncontrolled severe asthma regardless of the T2 endotype. Furthermore, tezepelumab is a safe drug and can be ‘self-administered’ using a pre-filled, disposable pen.
One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study
Published in Journal of Asthma, 2023
Masaharu Shinkai, Motohiro Ebisawa, Yasushi Fukushima, Satomi Takeuchi, Hiroshi Okada, Tatsuro Tokiyo, Nobuya Hayashi, Mami Takikawa, Gene Colice, Gun Almqvist
AESIs reported during the on-treatment period are described in Supplementary Table 4. Severe infections were reported in nine (13.8%) patients during the on-treatment period and included herpes zoster and oral herpes (two [3.1%] patients each), and viral gastroenteritis, genital herpes simplex, influenza, lung abscess, and tonsillitis (one [1.5%] patient each). None of these events were assessed by the investigator as causally related to tezepelumab. Injection site reactions occurred in two patients (3.1%) and were classed as mild, non-serious AEs of injection site erythema on the abdominal wall, which were assessed by the investigator to be causally related to tezepelumab administration. During the study, no AESIs of opportunistic infection, helminth infection, anaphylactic reaction, hypersensitivity, malignancy, or Guillain–Barré syndrome were reported, and no patient had confirmed immune complex disease. The male patient had a mild, non-serious AE of drug-induced liver injury on Day 171, but this was attributed to bepridil hydrochloride monohydrate that was used to treat an AE of atrial fibrillation and was assessed by the investigator to be unrelated to tezepelumab.