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Health Technology Assessment... Jan 2024Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus).
OBJECTIVES
To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib).
DATA SOURCES
Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review.
METHODS
A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources.
RESULTS
Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost.
CONCLUSIONS
The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations.
FUTURE WORK AND LIMITATIONS
The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42021266219.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in ; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.
Topics: Child; Adult; Adolescent; Humans; Child, Preschool; Dermatitis, Atopic; Cyclosporine; State Medicine; Treatment Outcome; Cost-Benefit Analysis; Eczema; Antibodies, Monoclonal; Purines; Heterocyclic Compounds, 3-Ring; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38343072
DOI: 10.3310/LEXB9006 -
Biomolecules Mar 2024Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to... (Review)
Review
Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to in our daily lives can alter sterol biosynthesis. These also encompass various classes of FDA-approved medications, including (but not limited to) commonly used antipsychotic, antidepressant, antifungal, and cardiovascular medications. These medications can interfere with various enzymes of the post-lanosterol biosynthetic pathway, giving rise to complex biochemical changes throughout the body. The consequences of these short- and long-term homeostatic disruptions are mostly unknown. We performed a comprehensive review of the literature and built a catalogue of chemical agents capable of inhibiting post-lanosterol biosynthesis. This process identified significant gaps in existing knowledge, which fall into two main areas: mechanisms by which sterol biosynthesis is altered and consequences that arise from the inhibitions of the different steps in the sterol biosynthesis pathway. The outcome of our review also reinforced that sterol inhibition is an often-overlooked mechanism that can result in adverse consequences and that there is a need to develop new safety guidelines for the use of (novel and already approved) medications with sterol biosynthesis inhibiting side effects, especially during pregnancy.
Topics: Animals; Humans; Biosynthetic Pathways; Cholesterol; Lanosterol; Sterols
PubMed: 38672427
DOI: 10.3390/biom14040410 -
Patient Preference and Adherence 2020Medication-induced oral hyperpigmentation is an oral condition that impacts patients' quality of life and has been linked to many systemic therapeutic agents. The exact... (Review)
Review
BACKGROUND
Medication-induced oral hyperpigmentation is an oral condition that impacts patients' quality of life and has been linked to many systemic therapeutic agents. The exact pathogenesis of tissue pigmentation varies greatly and is not completely known. This systematic review aimed to present data on the causal association between medications and the development of oral/mucosal pigmentation as an adverse drug reaction.
METHODS
A systematic review and analysis of literature were conducted using the following databases: PubMed, Science Direct, ProQuest, Web of Science, and Scopus. The systematic review included original articles written in English and published between January 1982 and June 2020. Following the PRISMA statement, eligible articles were systematically reviewed, and data were extracted from eligible studies and analyzed.
RESULTS
A total of 235 articles were identified, of which 57 met the inclusion criteria and were included in this review. The mean age of included patients was 46.2±16.38 years (range: 10-90 years) with a male to female ratio of 1:1.45. Oral mucosal hyperpigmentation was reported following the use of several classes of medications such as antiviral (eg, zidovudine), antibiotic (eg, minocycline), antimalarial (eg, chloroquine), anti-fungal (eg, ketoconazole), antileprotic (eg, clofazimine), antihypertensive (eg, amlodipine), chemotherapeutic, and antineoplastic drugs. The risk of developing oral pigmentation was significantly higher with antimalarial medications, antibiotics, antineoplastic and chemotherapeutic agents. Medication-induced oral hyperpigmentation was most frequent among women and in the hard palate.
CONCLUSION
Future research is warranted to better understand the pathogenesis and risk factors for medication-induced oral hyperpigmentation in order to reassure patients during prescription and management.
PubMed: 33116439
DOI: 10.2147/PPA.S275783 -
JAMA Dermatology Oct 2022Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians...
IMPORTANCE
Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD.
OBJECTIVE
To develop recommendations for the safe and effective use of LADD.
EVIDENCE REVIEW
A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved.
FINDINGS
Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections.
CONCLUSIONS AND RELEVANCE
This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.
Topics: Adult; Humans; Adolescent; Pharmaceutical Preparations; Carcinoma, Squamous Cell; Antifungal Agents; Skin Neoplasms; Lasers; Antiviral Agents
PubMed: 35976634
DOI: 10.1001/jamadermatol.2022.3234 -
Cureus Oct 2021Antifungals are effective antimicrobial agents broadly used in medical practice. Severe acute liver failure from oral or IV administration of antifungals is a rare but... (Review)
Review
Antifungals are effective antimicrobial agents broadly used in medical practice. Severe acute liver failure from oral or IV administration of antifungals is a rare but long-standing clinical challenge. We aimed to approximate the risk of clinical acute liver injury among users of oral antifungals in the general population. This review was completed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Six articles were included, comprising case reports and cohort studies, after eliminating duplicate publications. No randomized control studies were found. In all studies, the duration of antifungal use was associated with significantly increased liver enzyme levels. Although it is not very common for patients on antifungals to develop acute liver failure, the prognosis is often good with swift discontinuation of the drug and proper treatment. Liver function evaluation before treatment and periodic monitoring every three to six weeks after commencement of treatment is suggested.
PubMed: 34703680
DOI: 10.7759/cureus.18940 -
The Cochrane Database of Systematic... Sep 2022Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of... (Review)
Review
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review.
OBJECTIVES
The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials.
SELECTION CRITERIA
Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The searches identified six trials; none of which met the inclusion criteria for the review.
MAIN RESULTS
We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update.
AUTHORS' CONCLUSIONS
At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Cystic Fibrosis; Humans; Itraconazole
PubMed: 36053129
DOI: 10.1002/14651858.CD002204.pub5 -
Frontiers in Cellular and Infection... 2022Invasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a... (Review)
Review
PURPOSE
Invasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a new triazole antifungal agent that has shown promising efficacy in the prophylaxis and treatment of invasive fungal diseases. The aim of this review is to summarize the recent real-world experiences of using ISA for the treatment and prevention of IFD.
METHODS
We performed a comprehensive literature search of the MEDLINE, PubMed, Embase, and Cochrane databases for clinical applications of ISA in the real world. Tables and reference lists are presented for this systematic review.
RESULTS
IFD poses a major threat to public health and causes high mortality rates. ISA may provide a good treatment. For example, the efficacy of ISA in the treatment of invasive aspergillosis (IA) is comparable to that of voriconazole, and its efficacy in the treatment of invasive mucormycosis (IM) is similar to that of liposomal amphotericin B (L-AmB); therefore, ISA is recommended as the first-line treatment for IA and IM. ISA can also achieve good efficacy in the treatment of invasive candidiasis (IC) and can be used as an alternative to de-escalation therapy after first-line drug therapy. In addition, most studies have shown the efficacy and safety of ISA for the prophylaxis of IFD.
CONCLUSION
Taken together, ISA are expected to become a new choice for the treatment and prevention of IFD because of their good tolerability, high bioavailability, and few drug interactions.
Topics: Humans; Triazoles; Invasive Fungal Infections; Nitriles; Antifungal Agents; Aspergillosis; Mucormycosis; Candidiasis, Invasive
PubMed: 36530445
DOI: 10.3389/fcimb.2022.1049959 -
Indian Journal of Dermatology 2023is an important causative organism of opportunistic fungal infection, and it is a growing medical concern due to the increasing usage of broad-spectrum antibiotics,... (Review)
Review
is an important causative organism of opportunistic fungal infection, and it is a growing medical concern due to the increasing usage of broad-spectrum antibiotics, immunosuppressant agents, and other immunocompromising conditions. Currently, bLf and antifungal drugs have been known to have synergistic effects, increasing the drug's efficacy. This study aims to investigate the efficacy of the synergistic effect of bLf and antifungal drugs. This review addressed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We conducted literature searches to assess the association of lactoferrin and current antifungal therapy against in ProQuest, PubMed, MEDLINE, EBSCOhost, SAGE, JSTOR, GARUDA, and Open Gray with no date restriction (until March 5, 2021). We used Jeffry's Amazing Statistical Program (JASP) to measure the overall size effect of MIC (minimum inhibitory concentration) between studies. A total of 7 studies retained were experimental in vitro studies. Based on the available data, 4 out of 7 studies were included in the quantitative analysis. This systematic review showed that bovine lactoferrin could help inhibit the development of azole-susceptible and azole-resistant . Furthermore, there was synergistic activity between lactoferrin and various antifungals. Our meta-analysis showed that lactoferrin could significantly inhibit the growth than the control group. Bovine lactoferrin and its peptide derivatives isolated from bovine milk can significantly inhibit the growth of , both susceptible to azoles and those with azole resistance.
PubMed: 38371540
DOI: 10.4103/ijd.ijd_275_22 -
Mycoses Feb 2022Patients with acute and chronic liver impairment are susceptible to invasive fungal infections such as candidemia and invasive pulmonary aspergillosis as a result of... (Review)
Review
Patients with acute and chronic liver impairment are susceptible to invasive fungal infections such as candidemia and invasive pulmonary aspergillosis as a result of cirrhosis-associated immune dysfunction, humoral immunodeficiency, cell-mediated dysfunction and systemic inflammation. Besides classical risk factors for invasive fungal infection, acute-on-chronic liver failure, corticosteroid use, gastrointestinal bleeding, and prophylactic use of antibiotics are all additional conditions which are related to the potential development of fungal infections. Therefore, high-risk patients should be carefully followed by microbiological surveillance including cultures but also by imaging and fungal biomarkers for providing early diagnosis. Echinocandins are still the mainstay and first line antifungal therapy in cases of invasive candidiasis. Due to concerns of liver toxicity and in cases of renal impairment liposomal amphotericin B is a suitable alternative to voriconazole in patients with invasive pulmonary aspergillosis. Although, data of isavucoanzole and posaconazole use in those patients are also promising more specific studies in the subgroup of patients with liver impairment are needed. Especially, due to the late diagnosis and multiple organ dysfunction usually present in patients with liver impairment morbidity and mortality rates remain high. Based on the broad spectrum of diverse reports with varying content and quality and in some cases lack of evidence we performed a systematic review on this topic.
Topics: Antifungal Agents; Candidiasis, Invasive; Graft vs Host Disease; Humans; Invasive Fungal Infections; Invasive Pulmonary Aspergillosis; Liver; Liver Diseases
PubMed: 34837414
DOI: 10.1111/myc.13403 -
Exploration of Targeted Anti-tumor... 2023One in eight fatalities globally are considered cancer-related. The need for cancer therapy is growing. Natural products continue to play a role in drug development, as... (Review)
Review
AIM
One in eight fatalities globally are considered cancer-related. The need for cancer therapy is growing. Natural products continue to play a role in drug development, as up to 50% of authorized drugs in the last 30 years have been isolated from natural sources.
METHODS
Anticancer, antioxidant, antibacterial, antifungal, antiviral, analgesic, anti-inflammatory, and other actions have all been reported in research papers using plants from the genus in the treatment and prevention of disease.
RESULTS
Results from the anticancer test showed that the genus, especially , and had significant promise as an anticancer agent against several cancer cell lines. Numerous factors, including phytochemical composition, increased apoptotic activity, decreased cell proliferation, stopped angiogenesis, and reduced inflammation.
CONCLUSIONS
These results, despite preliminary, show promise for further purification and investigation of bioactive compounds and extracts within the genus for their anticancer properties.
PubMed: 37205310
DOI: 10.37349/etat.2023.00134