S K Mahil1, M C Ezejimofor2, L S Exton2, L Manounah2, A D Burden3, L C Coates4, M de Brito1, A McGuire1, R Murphy5,6,7, C M Owen8, R Parslew9, R T Woolf1, Z Z N Yiu10, O A Uthman11, M F Mohd Mustapa2, C H Smith1. 1. St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, UK. 2. British Association of Dermatologists, London, W1T 5HQ, UK. 3. Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8QQ, UK. 4. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK. 5. Department of Dermatology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2JF, UK. 6. Department of Dermatology, Sheffield Children's NHS Foundation Trust, Sheffield, S10 3FL, UK. 7. University of Nottingham, University Park, Nottingham, NG7 2RD, UK. 8. Department of Dermatology, East Lancashire Hospitals NHS Trust, Burnley, BB10 2PQ, UK. 9. Department of Dermatology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, L7 8XP, UK. 10. Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, M13 9PT, UK. 11. Warwick Centre for Applied Health Research and Delivery, Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
Abstract
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.
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.
Authors: April W Armstrong; Ahmed M Soliman; Keith A Betts; Yan Wang; Yawen Gao; Luis Puig; Matthias Augustin Journal: Dermatol Ther (Heidelb) Date: 2021-03-31
Authors: April W Armstrong; Ahmed M Soliman; Keith A Betts; Yan Wang; Yawen Gao; Vassilis Stakias; Luis Puig Journal: Dermatol Ther (Heidelb) Date: 2021-12-04
Authors: Raymond Milan; Jacques LeLorier; Marie-Josée Brouillette; Anne Holbrook; Ivan V Litvinov; Elham Rahme Journal: Front Pharmacol Date: 2022-02-15 Impact factor: 5.810
Authors: Marija V Medovic; Vladimir Lj Jakovljevic; Vladimir I Zivkovic; Nevena S Jeremic; Jovana N Jeremic; Sergey B Bolevich; Ana B Ravic Nikolic; Vesna M Milicic; Ivan M Srejovic Journal: Oxid Med Cell Longev Date: 2022-03-12 Impact factor: 6.543