-
American Family Physician Apr 2022Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and... (Review)
Review
Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and a family history of ulcerative colitis. Diagnosis is suspected based on symptoms of urgency, tenesmus, and hematochezia and is confirmed with endoscopic findings of continuous inflammation from the rectum to more proximal colon, depending on the extent of disease. Fecal calprotectin may be used to assess disease activity and relapse. Medications available to treat the inflammation include 5-aminosalicylic acid, corticosteroids, tumor necrosis factor-alpha antibodies, anti-integrin antibodies, anti-interleukin-12 and -23 antibodies, and Janus kinase inhibitors. Choice of medication and method of delivery depend on the location and severity of mucosal inflammation. Other treatments such as fecal microbiota transplantation are considered experimental, and complementary therapies such as probiotics and curcumin have mixed data. Surgical treatment may be needed for fulminant or refractory disease. Increased risk of colorectal cancer and use of immunosuppressive therapies affect the preventive care needs for these patients.
Topics: Antibodies, Anti-Idiotypic; Colitis, Ulcerative; Fecal Microbiota Transplantation; Humans; Inflammation; Leukocyte L1 Antigen Complex
PubMed: 35426646
DOI: No ID Found -
International Journal of Molecular... May 2023Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE... (Review)
Review
Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), and anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) and real-life studies have been conducted to define their efficacy and identify baseline patients' characteristics potentially predictive of favorable outcomes. Switching to another monoclonal antibody is recommended in case of a lack of benefits. The aim of this work is to review the current knowledge on the impact of switching biological therapies in severe asthma as well as on predictors of treatment response or failure. Almost all of the information about switching from a previous monoclonal antibody to another comes from a real-life setting. In the available studies, the most frequent initial biologic was Omalizumab and patients who were switched because of suboptimal control with a previous biologic therapy were more likely to have a higher baseline blood eosinophil count and exacerbation rate despite OCS dependence. The choice of the most suitable treatment may be guided by the patient's clinical history, biomarkers of endotype (mainly blood eosinophils and FeNO), and comorbidities (especially nasal polyposis). Due to overlapping eligibility, larger investigations characterizing the clinical profile of patients benefiting from switching to different monoclonal antibodies are needed.
Topics: Humans; Omalizumab; Asthma; Antibodies, Monoclonal; Biological Therapy; Eosinophils; Anti-Asthmatic Agents
PubMed: 37298514
DOI: 10.3390/ijms24119563 -
World Journal of Gastroenterology Aug 2022Celiac disease (CeD) is a chronic gluten-induced enteropathy with plethoric manifestations. The typical manifestations of CeD such as chronic diarrhea and malabsorption... (Review)
Review
Celiac disease (CeD) is a chronic gluten-induced enteropathy with plethoric manifestations. The typical manifestations of CeD such as chronic diarrhea and malabsorption are widely recognized, however, many patients have atypical manifestations like iron deficiency anemia, idiopathic short stature, hypertransaminesemia or infertility, These patients often present to the primary care physicians and/or non-gastrointestinal specialties. However, due to a lack of awareness among the healthcare professionals about the various atypical manifestations, many patients are not screened for CeD. In this review, we have summarized the available literature about the prevalence of CeD in various gastrointestinal (chronic diarrhea) and non-gastrointestinal conditions (iron deficiency anemia, short stature, cryptogenic hypertransaminesemia, cryptogenic cirrhosis or idiopathic ataxia ) where the diagnosis of CeD should be con-sidered. In addition, we also discuss special scenarios where screening for CeD should be considered even in absence of symptoms such as patients with type 1 diabetes, Down's syndrome, and first-degree relatives of patients with CeD. Further, we discuss the diagnostic performance and limitations of various screening tests for CeD such as IgA anti-tissue transglutaminase antibodies, anti-endomysial antibodies and anti-deamidated gliadin antibodies. Based on the current recommendations, we propose a diagnostic algorithm for patients with suspected CeD.
Topics: Anemia, Iron-Deficiency; Antibodies, Anti-Idiotypic; Autoantibodies; Celiac Disease; Delivery of Health Care; Diarrhea; Gliadin; Humans; Immunoglobulin A; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases
PubMed: 36157923
DOI: 10.3748/wjg.v28.i32.4493 -
Medicina Clinica Nov 2023Urticaria is a skin-condition characterized by sudden-onset pruritic wheals with/without angioedema. Urticaria can be acute or chronic. Chronic urticaria may be... (Review)
Review
Urticaria is a skin-condition characterized by sudden-onset pruritic wheals with/without angioedema. Urticaria can be acute or chronic. Chronic urticaria may be spontaneous or inducible, based on absence/presence of specific triggers. Chronic spontaneous urticaria is most frequent (∼80%). Urticaria is primarily a mast-cell mediated histaminergic-disorder. Recently, other inflammatory cells and pro-inflammatory cytokines have been implicated. Deeper understanding has unmasked two endotypes - IgE-mediated type I autoimmunity/autoallergy and IgG-mediated type IIb autoimmunity. Current treatment recommendation involving second-generation H1-antihistamines, omalizumab and cyclosporine is effective in 60-80% patients. So, newer treatment options are being explored based on emerging targets. Despite being non-lethal, urticaria considerably impairs patient's quality-of-life and may be associated with extra-cutaneous comorbidities. Several "patient reported outcome measures" have been proposed to evaluate disease-activity, impact and control, for effective treatment modulation till complete disease control. This review discusses the current understanding about urticaria and its future directions, to facilitate optimum evidenced-based care.
Topics: Humans; Chronic Disease; Urticaria; Angioedema; Omalizumab; Skin
PubMed: 37537021
DOI: 10.1016/j.medcli.2023.06.026 -
The Journal of Allergy and Clinical... Sep 2020Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by IgE hyperproduction and eosinophilic inflammation. The anti-IgE antibody, omalizumab, has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by IgE hyperproduction and eosinophilic inflammation. The anti-IgE antibody, omalizumab, has demonstrated efficacy in patients with CRSwNP and comorbid asthma previously.
OBJECTIVE
Our aim was to determine omalizumab safety and efficacy in CRSwNP in phase 3 trials (POLYP 1 and POLYP 2).
METHODS
Adults with CRSwNP with inadequate response to intranasal corticosteroids were randomized (1:1) to omalizumab or placebo and intranasal mometasone for 24 weeks. Coprimary end points included change from baseline to week 24 in Nasal Polyp Score (NPS) and Nasal Congestion Score. Secondary end points included change from baseline to week 24 in Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test, sense of smell, postnasal drip, runny nose, and adverse events.
RESULTS
Patients in POLYP 1 (n = 138) and POLYP 2 (n = 127) exhibited severe CRSwNP and substantial quality of life impairment evidenced by a mean NPS higher than 6 and SNOT-22 score of approximately 60. Both studies met both the coprimary end points. SNOT-22 score, University of Pennsylvania Smell Identification Test score, sense of smell, postnasal drip, and runny nose were also significantly improved for omalizumab versus placebo. In POLYP 1 and POLYP 2, the mean changes from baseline at week 24 for omalizumab versus placebo were as follows: NPS, -1.08 versus 0.06 (P < .0001) and -0.90 versus -0.31 (P = .0140); Nasal Congestion Score, -0.89 versus -0.35 (P = .0004) and -0.70 versus -0.20 (P = .0017); and SNOT-22 score, -24.7 versus -8.6 (P < .0001) and -21.6 versus -6.6 (P < .0001). Adverse events were similar between groups.
CONCLUSION
Omalizumab significantly improved endoscopic, clinical, and patient-reported outcomes in severe CRSwNP with inadequate response to intranasal corticosteroids, and it was well tolerated.
Topics: Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Omalizumab; Rhinitis; Sinusitis; Treatment Outcome
PubMed: 32524991
DOI: 10.1016/j.jaci.2020.05.032 -
The Journal of Allergy and Clinical... Mar 2021Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend the use of the IgE-targeted biologic omalizumab in patients with antihistamine-refractory... (Review)
Review
Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend the use of the IgE-targeted biologic omalizumab in patients with antihistamine-refractory disease. The rationale for this is supported by the key role of IgE and its high-affinity receptor, FcεRI, in the degranulation of skin mast cells that drives the development of the signs and symptoms of CSU, itchy wheals, and angioedema. Here, we review the current understanding of the pathogenesis of CSU and its autoimmune endotypes. We describe the mechanisms of action of omalizumab, the only biologic currently approved for CSU, its efficacy and ways to improve it, biomarkers for treatment response, and strategies for its discontinuation. We provide information on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. Finally, we discuss targets for novel biologics and where we stand with their clinical development. These include IgE/ligelizumab, IgE/GI-310, thymic stromal lymphopoietin/tezepelumab, C5a receptor/avdoralimab, sialic acid-binding Ig-like lectin 8/lirentelimab, CD200R/LY3454738, and KIT/CDX-0159. Our aim is to provide updated information and guidance on the use of biologics in the treatment of patients with CSU, now and in the near future.
Topics: Anti-Allergic Agents; Biological Products; Chronic Disease; Chronic Urticaria; Humans; Omalizumab; Urticaria
PubMed: 33685605
DOI: 10.1016/j.jaip.2020.11.043 -
The Journal of Allergy and Clinical... Mar 2023Severe asthma in childhood confers substantial patient- and society-level burdens. Although biologics have been available for the management in adults and adolescents... (Review)
Review
Severe asthma in childhood confers substantial patient- and society-level burdens. Although biologics have been available for the management in adults and adolescents for nearly 20 years, research on the efficacy and safety of biologics in children and adolescents has lagged. Fortunately, more recent research specifically in children has provided an evidence base for biologic use in this age group. Most children with severe asthma demonstrate a type 2 inflammatory phenotype, the primary target of currently approved biologics. Three biologics, omalizumab, mepolizumab, and duplilumab, are Food and Drug Administration-approved for children as young as 6 years, whereas benralizumab and tezepelumab are approved for adolescents older than 12 years. All these agents reduce the rates of severe asthma exacerbations, whereas their effects on pulmonary function vary across agents. Safety profiles are reassuring, although additional long-term safety data in children are still needed. The choice of a biologic agent follows a careful assessment of other factors that contribute to uncontrolled asthma and includes biomarkers of blood eosinophils, fractional exhaled nitric oxide, allergic sensitization, and IgE levels. This review focuses on the underlying pathophysiology of childhood asthma, an approach to phenotyping patients, and the efficacy, safety, and use of biologics in children and adolescents with severe asthma.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Omalizumab; Biological Factors; Biological Products
PubMed: 36702649
DOI: 10.1016/j.jaci.2023.01.002 -
The New England Journal of Medicine Oct 2019In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose-response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H-antihistamines at approved or increased doses, alone or in combination with H-antihistamines or leukotriene-receptor antagonists.
METHODS
In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose-response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial.
RESULTS
A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose-response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged.
CONCLUSIONS
A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.).
Topics: Adult; Aged; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Immunoglobulin E; Male; Middle Aged; Omalizumab; Patient Acuity; Remission Induction; Urticaria; Young Adult
PubMed: 31577874
DOI: 10.1056/NEJMoa1900408 -
The Journal of Allergy and Clinical... Jan 2023Management of asthma in adults has advanced in the past 10 years. Central to these advances has been further clarification of type (T) 2 mechanisms of airway...
Management of asthma in adults has advanced in the past 10 years. Central to these advances has been further clarification of type (T) 2 mechanisms of airway inflammation and utilization of T2 biomarkers, that is, eosinophils and fractional exhaled nitric oxide. In addition, epithelial cells are emerging as significant contributors to inflammation through generation of alarmins to initiate local injury as well as downstream pathways. Five new biologics, mepolizumab, benralizumab, reslizumab, dupilumab, and tezepelumab, were approved to join omalizumab and revolutionize severe asthma treatment. These biologics significantly prevent exacerbations to spare systemic corticosteroids use and their side effects. Guidelines attest to the effectiveness of inhaled corticosteroids/long-acting β-agonists (formoterol) for both maintenance and rescue therapy. Focused updates to the Expert Panel Report addressed limited but specific questions relevant to asthma control. Future guidelines should include phenotype/endotype-directed therapeutics to gain more precision-directed treatment.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Omalizumab; Biological Products; Adrenal Cortex Hormones
PubMed: 36283607
DOI: 10.1016/j.jaip.2022.10.015 -
The Journal of Allergy and Clinical... May 2023Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. (Clinical Trial)
Clinical Trial
BACKGROUND
Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness.
OBJECTIVE
Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma.
METHODS
We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV value over 12 months of follow-up.
RESULTS
In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab.
CONCLUSIONS
Among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV value than omalizumab and mepolizumab.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Immunoglobulin E; Omalizumab; Comparative Effectiveness Research
PubMed: 36740144
DOI: 10.1016/j.jaci.2023.01.020