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Allergy Aug 2021This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed,...
This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.
Topics: Adult; Biological Products; Humans; Nasal Polyps; Omalizumab; Quality of Life; Sinusitis
PubMed: 33683704
DOI: 10.1111/all.14809 -
Current Medical Research and Opinion Nov 2020We conducted a systematic literature review (SLR) to determine the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyps (CRSwNP) and to describe...
OBJECTIVES
We conducted a systematic literature review (SLR) to determine the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyps (CRSwNP) and to describe how the addition of biologics has affected outcomes for patients with CRSwNP.
METHODS
The SLR adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase, MEDLINE, and Evidence-Based Medicine Reviews databases were searched using OVID. Relevant studies published between 1 January 2008 and 8 February 2019, for epidemiology, and 1 January 2008 and 16 February 2019, for clinical burden, and relevant conference abstracts from 1 January 2017 to 7 March 2019, for epidemiology and 1 January 2017-16 February 2019 for clinical burden were included.
RESULTS
For the epidemiology and clinical burden SLR, 147 and 119 records, respectively, met the inclusion criteria. We found the prevalence of CRSwNP was 1-2.6% and was greater in men. Asthma, allergy, and allergic rhinitis were the most common comorbidities identified. Reported risk factors included asthma, gene polymorphisms, age, and eosinophilia. Studies indicated that dupilumab, mepolizumab, and omalizumab each improved different clinical outcomes. Non-biologics (drugs such as corticosteroids or antibiotics, surgery, or aspirin desensitization) improved clinical outcomes as well.
CONCLUSIONS
CRSwNP is fairly prevalent in the general population. Despite the significant efficacy of existing treatments, several unmet needs remain. The high burden of uncontrolled symptoms, frequent recurrence of nasal polyps after surgery, and long-term adverse effects of oral corticosteroids indicate that new therapies addressing these unmet needs should be developed. Although data on biologics from randomized controlled trials look promising, the efficacy of biologics in the real world has yet to be established. The SLR of the epidemiology and clinical burden of CRSwNP revealed key gaps in the literature. There was a paucity of prevalence data across many geographic areas, and no prevalence projections could be determined. Studies showed varying efficacy of non-biologics and no studies directly compared biologics for efficacy. Data regarding clinical efficacy of agents for eosinophilic CRSwNP or severe CRSwNP were lacking, and these patient populations would be served by more trials.
Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Chronic Disease; Humans; Nasal Polyps; Omalizumab; Prevalence; Rhinitis; Risk Factors; Sinusitis; Treatment Outcome
PubMed: 32847417
DOI: 10.1080/03007995.2020.1815682 -
Allergy Jan 2021This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for...
This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CSU-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Ten RCTs including 1620 subjects aged 12 to 75 years old treated with omalizumab for 16 to 40 weeks were evaluated. Omalizumab 150 mg does not result in clinically meaningful improvement (high certainty) of the urticaria activity score (UAS)7 (mean difference (MD) -5; 95%CI -7.75 to -2.25), and the itch severity score (ISS)7 (MD -2.15; 95% CI -3.2 to -1.1) does not increase (moderate certainty) quality of life (QoL) (Dermatology Life Quality Index (DLQI); MD -2.01; 95%CI -3.22 to -0.81) and decreases (moderate certainty) rescue medication use (MD -1.68; 95%CI -2.95 to -0.4). Omalizumab 300 mg results in clinically meaningful improvements (moderate certainty) of the UAS7 (MD -11.05; 95%CI -12.87 to -9.24), the ISS7 (MD -4.45; 95%CI -5.39 to -3.51), and QoL (high certainty) (DLQI; MD -4.03; 95% CI -5.56 to -2.5) and decreases (moderate certainty) rescue medication use (MD -2.04; 95%CI -3.19 to -0.88) and drug-related serious AEs (RR 0.77; 95%CI 0.20 to 2.91).
Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Biological Products; Child; Chronic Urticaria; Humans; Middle Aged; Omalizumab; Quality of Life; Urticaria; Young Adult
PubMed: 32767573
DOI: 10.1111/all.14547 -
Dermatologic Therapy Nov 2020To examine the effectiveness of omalizumab on disease activity and quality of life in patients with cholinergic urticaria (CholU). Further, a systematic review of the...
To examine the effectiveness of omalizumab on disease activity and quality of life in patients with cholinergic urticaria (CholU). Further, a systematic review of the literature was performed to identify all studies of use of omalizumab in CholU. A total of 23 patients (63.9%) were refractory to updosed non-sedating antihistamines and initiated omalizumab in the observation period. Among these, an improvement of 10.8 UAS7 points (4.6-17.0), P = .002, was seen at 6 months follow up. DLQI and disease bother score VAS also improved significantly from before initiating treatment with omalizumab to follow-up; 7.0 points (3.6-10.3), P < .001 and 3.1 points (1.5-4.8), P = .001, respectively. The overall mean drug survival time for omalizumab (discontinued due to any cause) was 30.6 months (22.2-39.0). A total of five patients (21.7%) reported suspected side effects (headache, muscle pain, fatigue and injection site reactions) during treatment with omalizumab until 6 months follow-up. The systematic literature review identified 58 additional antihistamine refractory patients with CholU treated with omalizumab. The available studies reported that omalizumab is effective in patients with CholU and improves their disease-related quality of life. Omalizumab is safe, reduces disease activity and improves disease-related quality of life in patients with CholU.
Topics: Anti-Allergic Agents; Cholinergic Agents; Chronic Disease; Humans; Omalizumab; Prospective Studies; Quality of Life; Treatment Outcome; Urticaria
PubMed: 32654349
DOI: 10.1111/dth.14010 -
Clinical and Experimental Dermatology Dec 2020This review forms part of an annual update series on atopic eczema (AE), where systematic reviews (SRs) are gathered and appraised to provide a summary of key recent... (Comparative Study)
Comparative Study
This review forms part of an annual update series on atopic eczema (AE), where systematic reviews (SRs) are gathered and appraised to provide a summary of key recent research findings. The focus of this article is systemic therapies used in AE, while a review on prevention and topical therapies is provided in Part 1. In total, 17 SRs on various systemic treatments used in AE were first published or indexed in 2018. There is a lack of evidence to support vitamin D supplementation, montelukast and naltrexone in AE treatment. The adverse effects of systemic corticosteroids are the main barrier to their use, and there is also a lack of data to determine the optimal delivery and duration of treatment with them. Of other immunosuppressants, ciclosporin has the most robust evidence of efficacy. Biologic therapies in AE treatment are being increasingly investigated, and to date, the greatest quantity of data and evidence of efficacy relates to dupilumab. The most commonly reported adverse effects are injection-site reactions and conjunctivitis. Other biologics showing some evidence of efficacy include nemolizumab, lebrikizumab and tralokinumab, although further data are needed. There are currently insufficient data on oral small molecules, including Janus kinase inhibitors, in the treatment of AE. A Cochrane review on probiotics showed no significant benefit, and SRs and meta-analyses on complementary and alternative medicines, including probiotics, in paediatric AE demonstrated significant heterogeneity, thereby limiting their interpretation. This summary of recent SRs provides up-to-date evidence for clinicians on systemic therapies in AE.
Topics: Acetates; Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Therapy; Child; Complementary Therapies; Cyclopropanes; Cyclosporine; Cytochrome P-450 CYP1A2 Inducers; Dermatitis, Atopic; Eczema; Humans; Immunosuppressive Agents; Janus Kinase Inhibitors; Naltrexone; Narcotic Antagonists; Omalizumab; Placebo Effect; Probiotics; Quinolines; Sulfides; Ustekinumab; Vitamin D
PubMed: 32568435
DOI: 10.1111/ced.14304 -
The Journal of Allergy and Clinical... Oct 2020Symptomatic dermographism (SD), the most common form of chronic inducible urticaria, presents with transient wheals accompanied by itching in response to scratching.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Symptomatic dermographism (SD), the most common form of chronic inducible urticaria, presents with transient wheals accompanied by itching in response to scratching. Little is known about available treatment options and their efficacy in SD.
OBJECTIVE
To systematically review the efficacy of treatment options for patients with SD.
METHODS
Using predefined search terms, we searched for relevant literature published until September 2019. The systematic review process was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations.
RESULTS
The 23 studies identified included 15 randomized controlled trials; 22 and 17 assessed treatment responses in patients with SD by provocation/threshold testing and patient/physician clinical assessment, respectively. Thirteen different treatments were investigated in a total of 430 adult patients. The most frequently studied therapy, first-generation H-antihistamines, showed variable efficacy and significant side effects. In contrast, second-generation H-antihistamines (2AH), in all studies, were effective and well tolerated. Monotherapy with an H-antihistamine (AH) was not effective, whereas adding an AH increased the efficacy of treatment with an H-antihistamine (AH). SD improved with omalizumab. All other treatments were only investigated in small, unrepeated, and/or uncontrolled studies. There are no studies on updosing of 2AH.
CONCLUSIONS
The available SD studies are heterogeneous, mostly monocentric, old, small, and unrepeated, pointing to a high need for more and better studies. We suggest that 2AH should be the first-line treatment. In uncontrolled cases, the combination of AH and AH may be tried. Even though there is no evidence of its efficacy over standard dosage, updosing of 2AH may be considered based on the extrapolation of evidence from chronic spontaneous urticaria; omalizumab should be added in recalcitrant patients.
Topics: Adult; Chronic Disease; Chronic Urticaria; Histamine Antagonists; Histamine H1 Antagonists; Humans; Omalizumab; Urticaria
PubMed: 32473421
DOI: 10.1016/j.jaip.2020.05.016 -
Revista Alergia Mexico (Tecamachalco,... 2020Omalizumab is effective in the treatment of severe persistent allergic asthma that is not controlled with long-acting beta-agonists/ high-dose inhaled corticosteroids. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Omalizumab is effective in the treatment of severe persistent allergic asthma that is not controlled with long-acting beta-agonists/ high-dose inhaled corticosteroids.
OBJECTIVE
To conduct a systematic exploratory review and meta-analysis of studies with omalizumab in Latin America.
METHODS
A search of real-life studies on the effectiveness of omalizumab in asthma control conducted in Latin America was carried out. The average of the aggregate effectiveness of omalizumab in asthma control (Pooled Analysis) was estimated by using a random effects model.
RESULTS
Nine open uncontrolled observational studies were identified; these studies included a total of 1 118 patients with severe uncontrolled asthma. The average of the estimated aggregate effectiveness of omalizumab in the good control of severe asthma was of 80.6 % in children and 78.9 % in adults.
CONCLUSIONS
The average of the estimated aggregate effectiveness of omalizumab in the control of severe asthma in both children and adults in Latin America was over 78 %. Randomized controlled studies are required in order to establish the efficacy and effectiveness of omalizumab in the control of severe asthma and in the different subgroups by level of eosinophils.
Topics: Anti-Asthmatic Agents; Asthma; Humans; Latin America; Omalizumab; Severity of Illness Index; Treatment Outcome
PubMed: 32447864
DOI: 10.29262/ram.v67i1.701 -
American Journal of Therapeutics 2020Omalizumab has been proposed as a possible effective treatment of chronic spontaneous urticaria (CSU). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Omalizumab has been proposed as a possible effective treatment of chronic spontaneous urticaria (CSU).
STUDY QUESTION
We aimed to access the efficacy and safety of omalizumab in the treatment of CSU based on qualified, randomized controlled trials (RCTs).
DATA SOURCES
PubMed, the Cochrane library, and Embase databases.
STUDY DESIGN
Computerized search by index words was performed to identify qualified RCTs, and relevant literature sources were also searched.
RESULT
Nine RCTs were included in the meta-analysis with 1612 patients in the omalizumab group and 1251 patients in the placebo group. Compared with the placebo group, omalizumab significantly decreased the weekly itch score after therapy [Weighted Mean Difference (WMD), -3.94; 95% confidence interval (CI), -4.64 to -3.24], the weekly hive score (WMD, -5.27; 95% CI, -6.17 to -4.38), the dermatology life quality index (DLQI; WMD, -3.58; 95% CI, -4.66 to -2.50), and the urticaria activity score over 7 days (UAS7; WMD, -9.51; 95% CI, -10.94 to -8.08). There was no significant difference in the incidence of adverse events (AE) [relative risk (RR), 1.01; 95% CI, 0.91-1.12], serious AE (RR, 0.85; 95% CI, 0.57-1.27), and severe AE (RR, 0.83; 95% CI, 0.60-1.14) between the 2 groups. Compared with the placebo, omalizumab significantly decreased the weekly itch score and weekly hive score after therapy in patients receiving 75, 150, and 300 mg omalizumab, respectively. DLQI was significantly reduced in patients receiving 150 and 300 mg of omalizumab, respectively. In all the subgroup of UAS7, omalizumab significantly decreased the score compared with the placebo. Only patients receiving 600-mg omalizumab had a significantly higher AE incidence versus placebo. There was no significant difference in serious and severe AE between the 2 groups.
CONCLUSION
Omalizumab caused a significantly greater reduction in weekly itch score, weekly hive score, DLQI, and UAS7 in CSU patients than the placebo. However, high-quality, multicenter RCTs with a larger sample size are needed to confirm the safety of omalizumab, and whether AEs are caused by omalizumab or other factors.
Topics: Anti-Allergic Agents; Chronic Urticaria; Humans; Omalizumab; Pruritus; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 32427616
DOI: 10.1097/MJT.0000000000000912 -
Allergy Jan 2021Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of...
Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.
Topics: Asthma; Biological Factors; Biological Products; Dermatitis, Atopic; Female; Humans; Infant, Newborn; Multicenter Studies as Topic; Omalizumab; Pregnancy
PubMed: 32189356
DOI: 10.1111/all.14282 -
The Journal of Allergy and Clinical... Jun 2020Delayed pressure urticaria (DPU) is characterized by recurrent erythematous and often painful swelling after the skin is exposed to sustained pressure. Treatment is...
BACKGROUND
Delayed pressure urticaria (DPU) is characterized by recurrent erythematous and often painful swelling after the skin is exposed to sustained pressure. Treatment is challenging. Antihistamines, the first-line and only approved treatment, are often not effective.
OBJECTIVE
To systematically review the treatment options for DPU.
METHOD
A literature search of electronic databases for all relevant articles published till April 29, 2019, was conducted using the search terms "delayed pressure urticaria" and "pressure urticaria." This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.
RESULTS
Twenty-one studies (8 randomized controlled trials [RCTs], 10 retrospective cohort studies, and 3 open-label prospective studies) were included. Second-generation H antihistamines (sgAHs) were effective in 3 RCTs. The combination of an sgAH and montelukast (2 RCTs) or an sgAH and theophylline (1 non-RCT) was more effective than the sgAH alone. The disease improved with omalizumab (4 non-RCTs), sulphones (3 non-RCTs), oral prednisolone (1 RCT and 2 non-RCTs), intravenous immunoglobulin (1 non-RCT), and gluten-free diet (1 non-RCT). There are no studies on updosing of antihistamines over standard dosage in DPU.
CONCLUSIONS
Overall, the quality of studies on DPU is low. Because of the lack of other evidence, antihistamines remain the first-line therapy. Updosing of sgAHs could be considered in patients with uncontrolled symptoms on the basis of the extrapolation of evidence from chronic spontaneous urticaria, even though there is no evidence of its efficacy over standard dosage. Addition of montelukast may be considered. Omalizumab or sulphones may be used in treatment-resistant patients. High-quality DPU studies should be conducted.
Topics: Anti-Allergic Agents; Chronic Disease; Chronic Urticaria; Histamine Antagonists; Humans; Omalizumab; Urticaria
PubMed: 32179196
DOI: 10.1016/j.jaip.2020.03.004