Abrocitinib, tralokinumab and upadacitinib for treating moderate-to-severe atopic dermatitis.

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 Health Technology Assessment; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.

Atopic dermatitis is one of the most common skin conditions in children but can also develop in adulthood. People with atopic dermatitis have dry, red (inflamed) skin that is also extremely itchy (pruritus). There is no cure for atopic dermatitis. Therapy starts with topical treatments that are applied to the skin, such as emollients. Severe forms of atopic dermatitis are often treated with systemic treatments, which are drugs that are provided as tablets or an injection. Ciclosporin A is often the first systemic therapy given. If atopic dermatitis does not get better with ciclosporin A, options available in the National Health Service are dupilumab and baricitinib. New therapies that have been evaluated in clinical trials for atopic dermatitis but have not been assessed for use in the National Health Service are abrocitinib, tralokinumab and upadacitinib. The aim of this project is to review the medical benefits, risks and value for money for the National Health Service of abrocitinib, tralokinumab and upadacitinib for the treatment of moderate-to-severe atopic dermatitis in a multiple technology appraisal. Our review found that: For children aged between 12 and 18 years, abrocitinib and a low dose of upadacitinib (15 mg) are good value for money for the National Health Service. For adults who need a first systemic treatment, upadacitinib is unlikely to be good value for money for the National Health Service. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, upadacitinib 15 mg and tralokinumab could be good value for money for the National Health Service if they are used on their own. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, but need to take it with steroid cream, abrocitinib 100 mg, upadacitinib 15 mg and tralokinumab could all be good value for money for the National Health Service.

Clinical effectiveness of interventions for treatment-resistant anxiety in older people: a systematic review.

BACKGROUND: Anxiety and related disorders include generalised anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder and phobic disorders (intense fear of an object or situation). These disorders share the psychological and physical symptoms of anxiety, but each disorder has its own set of characteristic symptoms. Anxiety disorders can be difficult to recognise, particularly in older people (those aged over 65 years). Older people tend to be more reluctant to discuss mental health issues and there is the perception that older people are generally more worried than younger adults. It is estimated that between 3 and 14 out of every 100 older people have an anxiety disorder. Despite treatment, some people will continue to have symptoms of anxiety. People are generally considered to be 'resistant' or 'refractory' to treatment if they have an inadequate response or do not respond to their first treatment. Older adults with an anxiety disorder find it difficult to manage their day-to-day lives and are at an increased risk of comorbid depression, falls, physical and functional disability, and loneliness. OBJECTIVE: To evaluate the effectiveness of pharmacological, psychological and alternative therapies in older adults with an anxiety disorder who have not responded, or have responded inadequately, to treatment. DATA SOURCES: Electronic databases (MEDLINE, MEDLINE In-Process and Other Non-Indexed citations, EMBASE, The Cochrane Library databases, PsycINFO and Web of Science) were searched from inception to September 2013. Bibliographies of relevant systematic reviews were hand-searched to identify additional potentially relevant studies. ClinicalTrials.gov was searched for ongoing and planned studies. REVIEW METHODS: A systematic review of the clinical effectiveness of treatments for treatment-resistant anxiety in older adults was carried out. RESULTS: No randomised controlled trial or prospective comparative observational study was identified meeting the prespecified inclusion criteria. Therefore, it was not possible to draw any conclusions on clinical effectiveness. LIMITATIONS: As no study was identified in older adults, there is uncertainty as to which treatments are clinically effective for older adults with an anxiety disorder who have not responded to prior treatment. The comprehensive methods implemented to carry out this review are a key strength of the research presented. However, this review highlights the extreme lack of research in this area, identifying no comparative studies, which is a marked limitation. CONCLUSIONS: Specific studies evaluating interventions in older adults with an anxiety disorder who have not responded to first-line treatment are needed to address the lack of evidence. The lack of evidence in this area means that older adults are perhaps receiving inappropriate treatment or are not receiving a particular treatment because there is limited evidence to support its use. At this time there is scope to develop guidance on service provision and, as a consequence, to advance the standard of care received by older adults with a treatment-resistant anxiety disorder in primary and secondary care. Evaluation of the relative clinical effectiveness and acceptability of pharmacological and psychological treatment in older adults with an anxiety disorder that has not responded to first-line treatment is key future research to inform decision-making of clinicians and patients. An important consideration would be the enrolment of older adults who would be representative of older adults in general, i.e. those with multiple comorbid physical and mental disorders who might require polypharmacy. STUDY REGISTRATION: The protocol for the systematic review is registered on PROSPERO (registration number CRD42013005612). FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Primary care based clinics for asthma.

BACKGROUND: Asthma is defined as the presence of variable airflow obstruction with symptoms (more than one of wheeze, breathlessness, chest tightness, cough). It is becoming increasingly common worldwide and this is especially true in higher income countries. In several of these countries there has been a move towards delivery of asthma care via primary care based asthma clinics. Such clinics deliver proactive asthma care sited within primary care, via regular, dedicated sessions which are usually nurse led and doctor supported. They include organised recall of patients on an asthma register and care usually comprises education, symptom review and guideline-based management. Despite the proliferation of such clinics, especially in countries such as the United Kingdom (UK), there is a paucity of evidence to support their use. This review sets out to look at the evidence for the effectiveness of asthma clinics. OBJECTIVES: To determine the effectiveness of organised asthma care delivered via primary care based asthma clinics. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials (last search December 2011) and reviewed reference lists of all primary studies for additional references. SELECTION CRITERIA: We included randomised controlled trials of primary care based asthma clinics with a parallel group design, where clinics took place within dedicated time slots and included face-to-face interaction with doctor or nurse and control groups received usual clinical practice care by a general practitioner. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials for inclusion and conducted all data extraction and analysis. All disagreements were resolved by discussion. MAIN RESULTS: A total of three studies involving 466 participants were included. There was no statistically significant difference between the asthma clinic group and the control group for most outcomes (primary outcomes: asthma exacerbations leading to hospitalisation or accident and emergency (A&E) visit, use of reliever and preventer medication, quality of life; secondary outcomes: symptoms, time lost from work and withdrawals from the intervention or usual care). However, the confidence intervals were wide for all outcomes and there was substantial heterogeneity between the studies for both A&E visits and time lost from work. One study (101 patients) looked at nocturnal awakenings due to asthma and found a statistically significant reduction in the number of patients reporting this symptom in the asthma clinic group compared to the usual care group (OR 0.31; 95% CI 0.12 to 0.77). There were no studies looking at the secondary outcome of exacerbations requiring oral steroids. AUTHORS' CONCLUSIONS: There is limited evidence of efficacy for primary care based asthma clinics, and firm conclusions cannot be formed until more good quality trials have been carried out.