The landscape of psoriasis provision in the UK.

Psoriasis remains one of the commonest conditions seen in dermatological practice, and its treatment is one of the greatest cost burdens for the UK National Health Service. Treatment of psoriasis is complex, with numerous overlapping lines and therapies used in combination. This complexity reflects the underlying pathophysiology of the disease as well as the heterogeneous population that it affects. National Institute for Health and Care Excellence (NICE) guidance for the treatment of psoriasis has been available since 2013, and has been the subject of three national audits conducted by the British Association of Dermatologists. This report synthesizes the results of the most recent of those exercises and places it in the context of the NICE guidance and previous audits. It clearly shows the significant burden of disease, issues with provision of services and long waiting times and the marked shift in therapies towards targeted biologic therapies

British Association of Dermatologists National Clinical Audit on the Management of Hidradenitis Suppurativa in the UK.

BACKGROUND: The first UK guidelines for the management of hidradenitis suppurativa (HS) were published by the British Association of Dermatologists (BAD) in 2018. The guidelines contained a set of audit criteria. AIM: To evaluate current HS management against the audit standards in the BAD guidelines. METHODS: BAD members were invited to complete audit questionnaires between January and May 2020 for five consecutive patients with HS per department. RESULTS: In total, 88 centres participated, providing data for 406 patients. Disease staging using the Hurley system and disease severity using a validated tool during follow-ups was documented in 75% and 56% of cases, respectively, while quality of life and pain were documented in 49% and 50% of cases, respectively. Screening for cardiovascular disease risk factors was as follows: smoking 75%, body mass index 27% and others such as lipids and diabetes 57%. Screening for depression and anxiety was performed in 40% and 25% of cases, respectively. Support for smokers or obese patients was documented in 35% and 23% of cases. In total, 182 patients were on adalimumab, of whom 68% had documentation of baseline disease severity, and 76% were reported as having inadequate response or contraindications to systemic treatments; 44% of patients continued on adalimumab despite having < 25% improvement in lesion count. CONCLUSION: UK dermatologists performed well against several audit standards, including documenting disease staging at baseline and smoking status. However, improvements are needed, particularly with regard to screening and management of comorbidities that could reduce the long-term complications associated with HS. A re-audit is required to evaluate changes in practice in the future

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor

Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity. For sensing EGFR activity in cells, we used a genetically encoded CrkII-based biosensor which undergoes conformational changes upon tyrosine-221 phosphorylation by EGFR. We transfected this biosensor into EGFR-positive tumour cells using targeted lipopolyplexes bearing EGFR-binding peptides at their surfaces. In a murine model of basal-like breast cancer, we demonstrated a significant degree of intratumoral heterogeneity in EGFR activity, as well as the pharmacodynamic effect of a radionuclide-labeled EGFR inhibitor in situ. Furthermore, a significant correlation between high EGFR activity in tumour cells and macrophage-tumour cell proximity was found to in part account for the intratumoral heterogeneity in EGFR activity observed. The same effect of macrophage infiltrate on EGFR activation was also seen in a colorectal cancer xenograft. In contrast, a non-small cell lung cancer xenograft expressing a constitutively active EGFR conformational mutant exhibited macrophage proximity-independent EGFR activity. Our study validates the use of this methodology to monitor therapeutic response in terms of EGFR activity. In addition, we found iNOS gene induction in macrophages that are cultured in tumour cell-conditioned media as well as an iNOS activity-dependent increase in EGFR activity in tumour cells. These findings point towards an immune microenvironment-mediated regulation that gives rise to the observed intratumoral heterogeneity of EGFR signalling activity in tumour cells in vivo

Comparing the efficacy and tolerability of biologic therapies in psoriasis: an updated network meta-analysis

Background The rapid expansion of psoriasis biologics has led to an urgent need to understand their relative efficacy and tolerability to inform treatment decisions better and, specifically, to inform guideline development. Objectives To update a 2017 meta‐analysis on the comparative efficacy and tolerability of biologic treatments for psoriasis. Methods We searched the MEDLINE, PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs), published up to 7 September 2018, of 11 licensed, NICE‐approved biologics targeting tumour necrosis factor (adalimumab, etanercept, infliximab, certolizumab pegol), interleukin (IL)‐12/IL‐23p40 (ustekinumab), IL‐17A (secukinumab, ixekizumab), IL‐17RA (brodalumab) and IL‐23p19 (guselkumab, tildrakizumab, risankizumab). A frequentist network meta‐analysis ascertained direct or indirect evidence comparing biologics with one another, methotrexate or placebo. This was combined with hierarchical cluster analyses to consider efficacy (≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) or Physician’s Global Assessment 0 or 1; PASI 75; Dermatology Life Quality Index improvement) and tolerability (drug withdrawal due to adverse events) outcomes at 10–16 weeks, followed by assessments of study quality, heterogeneity and inconsistency. Results We identified 62 RCTs presenting data on direct comparisons (31 899 participants). All biologics were efficacious compared with placebo or methotrexate at 10–16 weeks. Hierarchical cluster analyses revealed that adalimumab, brodalumab, certolizumab pegol, guselkumab, risankizumab, secukinumab, tildrakizumab and ustekinumab were comparable with respect to high short‐term efficacy and tolerability. Infliximab and ixekizumab clustered together, with high short‐term efficacy but relatively lower tolerability than the other agents, although the number of drug withdrawal events across the network was low, so these findings should be treated with caution. Conclusions Using our methodology we found that most biologics cluster together with respect to short‐term efficacy and tolerability, and we did not identify any single agent as ‘best’. These data need to be interpreted in the context of longer‐term efficacy, effectiveness data, safety, posology and drug acquisition costs when making treatment decisions.</p

Comparing the efficacy and tolerability of biologic therapies in psoriasis: an updated network meta-analysis

Background The rapid expansion of psoriasis biologics has led to an urgent need to understand their relative efficacy and tolerability to inform treatment decisions better and, specifically, to inform guideline development. Objectives To update a 2017 meta‐analysis on the comparative efficacy and tolerability of biologic treatments for psoriasis. Methods We searched the MEDLINE, PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs), published up to 7 September 2018, of 11 licensed, NICE‐approved biologics targeting tumour necrosis factor (adalimumab, etanercept, infliximab, certolizumab pegol), interleukin (IL)‐12/IL‐23p40 (ustekinumab), IL‐17A (secukinumab, ixekizumab), IL‐17RA (brodalumab) and IL‐23p19 (guselkumab, tildrakizumab, risankizumab). A frequentist network meta‐analysis ascertained direct or indirect evidence comparing biologics with one another, methotrexate or placebo. This was combined with hierarchical cluster analyses to consider efficacy (≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) or Physician’s Global Assessment 0 or 1; PASI 75; Dermatology Life Quality Index improvement) and tolerability (drug withdrawal due to adverse events) outcomes at 10–16 weeks, followed by assessments of study quality, heterogeneity and inconsistency. Results We identified 62 RCTs presenting data on direct comparisons (31 899 participants). All biologics were efficacious compared with placebo or methotrexate at 10–16 weeks. Hierarchical cluster analyses revealed that adalimumab, brodalumab, certolizumab pegol, guselkumab, risankizumab, secukinumab, tildrakizumab and ustekinumab were comparable with respect to high short‐term efficacy and tolerability. Infliximab and ixekizumab clustered together, with high short‐term efficacy but relatively lower tolerability than the other agents, although the number of drug withdrawal events across the network was low, so these findings should be treated with caution. Conclusions Using our methodology we found that most biologics cluster together with respect to short‐term efficacy and tolerability, and we did not identify any single agent as ‘best’. These data need to be interpreted in the context of longer‐term efficacy, effectiveness data, safety, posology and drug acquisition costs when making treatment decisions.</p

British Association of Dermatologists guidelines for biologic therapy for psoriasis 2020: A rapid update

The overall aim of the guideline is to provide up‐to‐date, evidence‐based recommendations on the use of biologic therapies targeting TNF (adalimumab, etanercept, certolizumab pegol, infliximab), IL12/23p40 (ustekinumab), IL17A (ixekizumab, secukinumab), IL17RA (brodalumab) and IL23p19 (guselkumab, risankizumab, tildrakizumab) in adults, children and young people for the treatment of psoriasis; consideration is given to the specific needs of people with psoriasis and psoriatic arthritis