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Pediatric Rheumatology Online Journal Mar 2016Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition with an unclear pathophysiological mechanism affecting different parts of the... (Review)
Review
BACKGROUND
Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition with an unclear pathophysiological mechanism affecting different parts of the body. If untreated, the disease can lead to fibrosis and irreversible organ damage. IgG4-RD mostly has been described in adults, hence it is generally unknown among pediatricians. This systematic search of the literature provides an overview of all reports published on IgG4-RD in children in order to create awareness of IgG4-RD in pediatrics and to emphasize the broad clinical presentation of this disease.
METHODS
A systematic literature search of Embase, Medline, Web-of-Science, PubMed publisher, Cochrane and Google Scholar was performed for case reports on IgG4-RD in children.
RESULTS
Of total 740 articles identified by the search, 22 case reports including 25 cases of IgG4-RD in children were found. The median age of the children was 13 years, of which 64 % were girls. IgG4-related orbital disease (44 %) and autoimmune pancreatitis type 1/IgG4-related pancreatitis (12 %) predominantly occurred. Less frequently, other manifestations as pulmonary manifestation, cholangitis and lymphadenopathy were also found. Almost all cases were histologically proven. Prednisone was the first choice of treatment leading to favorable clinical response in 83 % of the cases. Maintenance therapy with steroid sparing agents was required in 43 % of the cases needing therapy. Rituximab was successful in all 4 cases, whereas, the disease modifying rheumatic drugs (DMARDs) mycophenolate mofetil, azathioprine and methotrexate were effective in almost 50 % of the cases.
CONCLUSION
IgG4-RD in children is a generally unknown disease among pediatricians, but several pediatric cases have been described. Prednisone is the first choice of treatment leading to disease remission in the majority of the cases. DMARDs and rituximab are alternative effective steroid sparing agents with more positive evidence for the latter.
Topics: Adolescent; Antibodies, Anti-Idiotypic; Autoimmune Diseases; Autoimmunity; Child; Humans; Immunoglobulin G; Inflammation
PubMed: 27012661
DOI: 10.1186/s12969-016-0079-3 -
American Journal of Rhinology & Allergy 2015Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and asthma are strongly associated, and patients suffering from both diseases are often difficult to treat.... (Review)
Review
BACKGROUND
Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and asthma are strongly associated, and patients suffering from both diseases are often difficult to treat. However, no guidelines about the management of patients with CRS and coexisting asthma exist.
OBJECTIVE
The purpose of this systematic review was to evaluate the management of CRSwNP and coexisting asthma.
METHODS
We systematically searched electronic databases and included clinical trials in which the clinical outcomes after medical or surgical treatment of patients with CRSwNP and asthma were assessed. The strength of the evidence for each outcome was graded on the basis of study quality and consistency in findings.
RESULTS
We included seven trials in which the effect of montelukast, omalizumab, erythromycin, and functional endoscopic sinus surgery (FESS) were studied in 317 adults with CRSwNP and asthma. All the interventions improved the majority of subjective and objective nasal outcomes significantly. However, few studies found significant effects on pulmonary function tests. The strength of the evidence was low overall.
CONCLUSION
Both FESS and medical interventions with systemic anti-inflammatory drugs improved nasal outcomes, although their efficacy in relation to the lower airways remains unclear. A low number of studies met inclusion criteria for this systematic review, which emphasizes the need for high-quality trials to explore the treatment of patients with CRSwNP and coexisting asthma.
Topics: Acetates; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Endoscopy; Humans; Leukotriene Antagonists; Nasal Polyps; Omalizumab; Quality of Life; Quinolines; Rhinitis; Sinusitis; Sulfides
PubMed: 25975250
DOI: 10.2500/ajra.2015.29.4178 -
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 -
The Cochrane Database of Systematic... Mar 2018Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere.
OBJECTIVES
To assess the effects of pharmacotherapy and behavioural interventions enacted in anticipation of school return during autumn that are designed to reduce asthma exacerbations in children during this period.
SEARCH METHODS
We searched the Cochrane Airways Group Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, reference lists of primary studies and existing reviews, and manufacturers' trial registries (Merck, Novartis and Ono Parmaceuticals). We searched databases from their inception to 1 December 2017, and imposed no restriction on language of publication.
SELECTION CRITERIA
We included all randomised controlled trials comparing interventions aimed specifically at reducing autumn exacerbations with usual care, (no systematic change in management in preparation for school return). We included studies providing data on children aged 18 years or younger.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently screened records identified by the search and then extracted data and assessed bias for trials meeting the inclusion criteria. A third review author checked for accuracy and mediated consensus on disagreements. The primary outcome was proportion of children experiencing one or more asthma exacerbations requiring hospitalisation or oral corticosteroids during the autumn period.
MAIN RESULTS
Our searches returned 546 trials, of which five met our inclusion criteria. These studies randomised 14,252 children to receive either an intervention or usual care. All studies were conducted in the Northern Hemisphere. Three interventions used a leukotriene receptor antagonist, one used omalizumab or a boost of inhaled corticosteroids, and the largest study, (12,179 children), used a medication reminder letter. Whilst the risk of bias within individual studies was generally low, we downgraded the evidence quality due to imprecision associated with low participant numbers, poor consistency between studies, and indirect outcome ascertainment.A US study of 513 children with mild/severe asthma and allergic sensitisation was the only study to provide data for our primary outcome. In this study, the proportion of participants experiencing an exacerbation requiring oral corticosteroids or hospital admission in the 90 days after school return was significantly reduced to 11.3% in those receiving omalizumab compared to 21.0% in those receiving placebo (odds ratio 0.48, 95% confidence interval 0.25 to 0.92, moderate-quality evidence). The remaining studies used alternative exacerbation definitions. When data from two leukotriene receptor antagonist studies with comparable outcomes were combined in a random-effects model, there was no evidence of an effect upon exacerbations. There was no evidence that a seasonal medication reminder letter decreased unscheduled contacts for a respiratory diagnosis between September and December.Four studies recorded adverse events. There was no evidence that the proportion of participants experiencing at least one adverse event differed between intervention and usual care groups. Lack of data prevented planned subgroup and sensitivity analyses.
AUTHORS' CONCLUSIONS
Seasonal omalizumab treatment from four to six weeks before school return might reduce autumn asthma exacerbations. We found no evidence that this strategy is associated with increased adverse effects other than injection site pain, but it is costly. There were no data upon which to judge the effect of this or other seasonal interventions on asthma control, quality of life, or asthma-related death. In future studies definitions of exacerbations should be provided, and standardised where possible. To investigate possible differential effects according to subgroup, participants in future trials should be well characterised with respect to baseline asthma severity and exacerbation history in addition to age and gender.
Topics: Acetates; Adrenal Cortex Hormones; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Behavior Therapy; Child; Chromones; Cyclopropanes; Disease Progression; Humans; Leukotriene Antagonists; Omalizumab; Quinolines; Randomized Controlled Trials as Topic; Seasons; Sulfides
PubMed: 29518252
DOI: 10.1002/14651858.CD012393.pub2 -
Medicine May 2019A wide range of pharmacological and nonpharmacological interventions for chronic urticaria (CU) have been evaluated in systematic reviews (SRs). We conducted an umbrella... (Comparative Study)
Comparative Study
A wide range of pharmacological and nonpharmacological interventions for chronic urticaria (CU) have been evaluated in systematic reviews (SRs). We conducted an umbrella review of SRs of the effectiveness and safety of pharmacological and nonpharmacological interventions for CU, which allow the findings of separate reviews to be compared and contrasted and thereby provide decision makers in healthcare with the evidence they need.We included SRs evaluating pharmacological and nonpharmacological interventions for CU. Comprehensive searches were conducted in 7 bibliographic databases, relevant journals up to July 2018. Two reviewers independently assessed the studies' relevance and quality. The assessment of multiple systematic reviews tool and grading of recommendations assessment, development and evaluation method was used to assess the methodological quality of the SRs and classify the quality of the outcomes.In total, 41 SRs were included. Thirty-seven reviews performed quantitative research syntheses, and 4 reviews performed qualitative research syntheses. The majority of SRs evaluated interventions based on combination therapies, antihistamines, traditional Chinese medicines, autohemotherapy, omalizumab, acupuncture, cyclosporine, and leukotriene receptor antagonist. Positive intervention outcomes were reported in the majority (75.32%) of the reviews. However, the methodological quality and evidence quality of the reviews were generally poor.There is some evidence to support a variety of interventions for CU. However, there was much heterogeneity in evidence quality among SRs. Many of the SRs had methodological weaknesses that make them vulnerable to bias. Moreover, there remained little information on the relative effectiveness of one intervention compared with another. Therefore, further SRs that adherence to strict scientific methods are necessary, and primary studies make comparisons between the different treatment options directly.
Topics: Acupuncture Therapy; Anti-Allergic Agents; Chronic Disease; Cyclosporine; Decision Making; Female; Histamine Antagonists; Humans; Immunosuppressive Agents; Leukotriene Antagonists; Male; Medicine, Chinese Traditional; Omalizumab; Quality Improvement; Treatment Outcome; Urticaria
PubMed: 31096521
DOI: 10.1097/MD.0000000000015711 -
Pharmacotherapy Apr 2017Omalizumab is recombinant humanized monoclonal antibody to immunoglobulin E. Guidelines for the treatment of chronic idiopathic urticaria (also known as chronic... (Review)
Review
Omalizumab is recombinant humanized monoclonal antibody to immunoglobulin E. Guidelines for the treatment of chronic idiopathic urticaria (also known as chronic spontaneous urticaria) recommend the use of omalizumab as third-line therapy in addition to high doses of histamine receptor type 1 (H ) antihistamines when they are unsuccessful as first- and second-line therapy. We performed a systematic review of the literature to identify studies that evaluated the efficacy of omalizumab for the treatment of chronic idiopathic urticaria, in both controlled and real-world settings, to assess its potential role as a preferred therapy. The PubMed, ScienceDirect, LILACS (Latin American and Caribbean Health Sciences Literature), and Google Scholar databases were searched between January 1, 2000, and November 21, 2016. The search was limited to articles published in peer-reviewed journals in the English language, and 29 studies were included in this review. Omalizumab 300 mg administered every 4 weeks appears to be the most effective and safe dosage, with a rapid response time, for the treatment of chronic idiopathic urticaria, with few minor adverse effects, and appears to be safe in the offspring of pregnant patients who received the drug. However, as published studies of omalizumab are sparse, future studies are warranted. When findings are confirmed in larger studies, due to its efficacy, safety, and increased benefit/cost ratio, omalizumab could become the preferred method of treatment for chronic idiopathic urticaria in patients unresponsive to H antihistamines.
Topics: Anti-Allergic Agents; Chronic Disease; Dose-Response Relationship, Drug; Humans; Immunoglobulin E; Omalizumab; Urticaria
PubMed: 28226418
DOI: 10.1002/phar.1915 -
American Journal of Otolaryngology 2022The management of chronic rhinosinusitis with nasal polyps (CRSwNP) is challenging due to disease recurrence and adverse effects. Both surgical and medical treatment... (Review)
Review
The management of chronic rhinosinusitis with nasal polyps (CRSwNP) is challenging due to disease recurrence and adverse effects. Both surgical and medical treatment modalities impact the quality of patients' lives. Monoclonal antibody treatment has recently been used successfully in CRS with limited reported adverse events. We aimed to review the literature to shed more light on the safety and adverse events associated with the biological therapy of CRSwNP. A comprehensive systematic review was conducted on the safety of different biological treatments when used for managing CRSwNP. We have included 13 studies in the present systematic review, including 12 randomized controlled trials (RCTs) and one cross-sectional study. The total sample size for the included studies was 2282 patients. Six studies investigated the safety and adverse events of dupilumab; three investigated omalizumab, three investigated mepolizumab, and only one investigated reslizumab. Some studies have reported that adverse events were common with these types of drugs. However they were not specific and self-limited. Headaches, injection site reactions, and pharyngitis were the most common adverse events found among the reported adverse events. The Dupilumab trial reported pharyngitis in 225 patients (22.4 %) followed by erythema in 9.4 %, headache in 8.1 %, epistaxis in 5.1 %, and asthma in 1.7 % of patients. Trials which used omalizumab reported headaches, nasal pharyngitis, injection-site reactions to be the most common adverse events with estimated prevalence rates of 8.1 %, 5.9 %, and 5.2 %, respectively. Mepolizumab and reslizumab studies reported that 40 % of patients were complicated by nasal polyps/congestion/pharyngitis/infections, 14 had a headache (15.5 %), two developed asthma (2.2 %), and only one patient (1.1 %) had epistaxis as an adverse event. Although the literature's current investigations indicate the safety of the biologic treatment modalities, further studies are needed as some uncertainty among the trials have been reported.
Topics: Humans; Nasal Polyps; Rhinitis; Omalizumab; Epistaxis; Sinusitis; Chronic Disease; Biological Therapy; Asthma; Antibodies, Monoclonal; Biological Products; Headache; Pharyngitis; Quality of Life
PubMed: 36057193
DOI: 10.1016/j.amjoto.2022.103615 -
Dermatologic Therapy Dec 2022This meta-analysis aimed to assess the efficacy of omalizumab in the treatment of refractory-to-antihistamines chronic induced urticaria (CIndU) in comparison with that... (Meta-Analysis)
Meta-Analysis Review
This meta-analysis aimed to assess the efficacy of omalizumab in the treatment of refractory-to-antihistamines chronic induced urticaria (CIndU) in comparison with that of refractory-to-antihistamines chronic spontaneous urticaria (CSU). We retrieved interventional studies and observational studies on omalizumab efficacy to CIndU patients and efficacy comparison between CSU and CIndU both refractory to H1-antihistamines in electronic databases (accessed till May 2022). The odd ratio (OR) and 95% confidence interval (CI) was calculated with a random-effect model in this meta-analysis. The majority of patients with different CIndU subtypes gained complete or partial response and good safety after omalizumab treatment. A total of five studies with 355 CSU patients and 103 CIndU patients were included for the meta-analysis. There was no significant difference in the efficacy of omalizumab in the treatment of CSU and CIndU (OR -0.83, 95% CI [0.84, 2.21], P > 0.05). Based on the validity of omalizumab in the treatment of various CIndU subtypes and non-differential efficacy between CSU and CIndU, it is reasonable to list omalizumab as a third-line treatment of refractory CIndU.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Urticaria; Chronic Disease; Chronic Urticaria; Histamine Antagonists; Treatment Outcome
PubMed: 36222320
DOI: 10.1111/dth.15928 -
Rhinology Dec 2021Allergic rhinitis (AR), an IgE mediated inflammatory disease, significantly impacts quality of life of a considerable proportion of the general population. Omalizumab, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allergic rhinitis (AR), an IgE mediated inflammatory disease, significantly impacts quality of life of a considerable proportion of the general population. Omalizumab, a humanized monoclonal antibody against IgE, has been evaluated for both seasonal and perennial AR. We aimed to assess the efficacy and safety of omalizumab in randomized controlled trials (RCTs) in inadequately controlled AR.
METHODS
We conducted a systematic literature search of RCTs evaluating the safety and efficacy of omalizumab in AR. We synthesized evidence for clinical improvement of AR symptoms, quality of life, reduction of the use of rescue medication, and adverse events.
RESULTS
The systematic search returned 289 articles, of which 12 RCTs were eligible for data extraction and meta-analysis. Omalizumab reduced the Daily Nasal Symptom Severity Score (DNSSS) by a summary standardized mean difference of -0.41 points with large heterogeneity; omalizumab significantly reduced the DNSSS both in the 3 cedar pollen-induced AR trials by -0.97 points and to a lower extent in the remaining five non-cedar trials by -0.19 points. Omalizumab also improved the Daily Ocular Symptom Severity Score (DOSSS) by a summary standardized mean difference of -0.30 points with large heterogeneity; the Rhino-conjunctivitis Quality of Life Questionnaire by a summary standardized mean difference of -0.45 points with no heterogeneity and the mean daily consumption of rescue antihistamines by a summary standardized mean difference of -0.21 with large heterogeneity. No statistically significant difference in the occurrence of adverse events was observed between omalizumab and placebo.
CONCLUSION
Our findings further support the efficacy and safety of omalizumab in the management of patients with allergic rhinitis inadequately controlled with a conventional treatment.
Topics: Antibodies, Monoclonal, Humanized; Humans; Nose; Omalizumab; Rhinitis, Allergic; Treatment Outcome
PubMed: 34714895
DOI: 10.4193/Rhin21.159 -
Journal of Cutaneous Medicine and... 2022Bullous pemphigoid (BP) is an autoimmune blistering skin disease. Current treatment strategies are limited by their efficacy and/or side effect profile and the need for...
Bullous pemphigoid (BP) is an autoimmune blistering skin disease. Current treatment strategies are limited by their efficacy and/or side effect profile and the need for safer and effective alternatives is undeniable. We aimed to conduct a systematic review focusing on the efficacy and safety of omalizumab in BP patients. Embase, PubMed, Cochrane, and clinicaltrials.gov were searched for English and French articles published from inception to July 1, 2021, using search terms "omalizumab" OR "Xolair" OR "IGE025" OR "olizumab" AND "bullous pemphigoid." Screening and data extraction was performed by two raters independently. The primary outcome was complete response (CR), and secondary outcomes were partial response (PR), flare-ups, adverse events/vital status. In total, 22 articles were included, with a total of 56 patients. All patients had a refractory BP with mean disease duration of 13.5 ± 20.2 months (Standard Deviation (SD)) and failed 3.1 ± 1.6 therapies and many remained corticosteroids dependent. Overall, 87.5% of patients responded to treatment (55.4% CR and 32.1% PR), 7.1% discontinued the protocol and only 5.4% were non responders. A third of patients were able to discontinue all other therapies and most others were able to discontinue or taper systemic corticosteroids to <10 mg daily. Flare-ups occurred in 57.7% of patients upon discontinuation of omalizumab and/or steroid tapering, most patients recaptured response thereafter. Omalizumab was well tolerated by most patients. Omalizumab appears to be a promising treatment for BP with a good response rate and safety profile. However, several limitations were identified in current literature, and highlight the need for randomized controlled trials of omalizumab in BP.
Topics: Autoimmune Diseases; Humans; Omalizumab; Pemphigoid, Bullous
PubMed: 35379011
DOI: 10.1177/12034754221089267