Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes.

INTRODUCTION: Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head. OBJECTIVES: To compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis. METHODS: A systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure. RESULTS: The NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors-brodalumab, ixekizumab, secukinumab-were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest. CONCLUSIONS: Despite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype.

The Cancer Drugs Fund in Practice and Under the New Framework.

BACKGROUND: The Cancer Drugs Fund (CDF) was established in 2010 to improve access to treatments not routinely available. Having widely overspent, stricter budgeting rules were introduced in 2016. The CDF can now only include treatments with potential to be cost effective once sufficient data are collected. OBJECTIVES: Our objective was to explore the process and criteria used for consideration of treatments under the new CDF framework and to describe the extent of evidence collection. METHODS: We identified CDF list, UK National Institute for Health and Care Excellence (NICE) and Scottish Medicines Consortium documents (10 May 2018). Data were collected on drugs and indications, reasons for inclusion in the CDF, data collection, incremental cost-effectiveness ratios (ICERs), and corresponding recommendations for Scotland. RESULTS: In total, 12 drugs were listed on the CDF in 17 indications, 12 of which were considered end-of-life care. The most common cancers were non-small-cell lung (n = 4), urothelial (n = 3), lymphocytic leukaemia (n = 2) and multiple myeloma (n = 2). The companies' ICERs were generally lower than those from the committee and the evidence review group. Drugs were included in the CDF for 6-42 months, with the majority included for ≥18 months. Data were frequently collected on overall survival (n = 16) and progression-free survival (n = 5) using NHS systems and, frequently, ongoing trials. CONCLUSIONS: Data collection frequently included overall survival and exceeded the 2 years recommended in the CDF strategy. It appears the CDF is allowing patients access to drugs long before they may become available for routine use. Our results are limited by the availability of published information and the small dataset.

Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response.

INTRODUCTION: New generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head studies. However, studies comparing these new biologics directly to one another are limited. OBJECTIVES: To compare the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis. METHODS: A systematic review was undertaken to identify randomised controlled trials evaluating biologic treatments, apremilast and dimethyl fumarate. MEDLINE, MEDLINE In-Process, Embase and the Cochrane Library were searched from the 1st January 2000 to 22nd November 2018. A Bayesian network meta-analysis (NMA) using a random-effects multinomial likelihood model with probit link and meta-regression to adjust for cross-trial variation in placebo responses compared the efficacy of interventions at inducing different levels of Psoriasis Area and Severity Index (PASI) response during the induction period. A range of sensitivity analyses was undertaken. RESULTS: Seventy-seven trials (34,816 patients) were included in the NMA. The base-case analysis showed that all active treatments were superior to placebo. IL-17 inhibitors, guselkumab and risankizumab were found to be more efficacious than tildrakizumab, ustekinumab, all TNF inhibitors and non-biologic systemic treatments at inducing all levels of PASI response. In addition, brodalumab, ixekizumab and risankizumab were significantly more efficacious than secukinumab; no significant difference was found in the comparison with guselkumab. The greatest benefit of brodalumab, ixekizumab, guselkumab, and risankizumab was seen for PASI 90 and PASI 100 response. Results were consistent across all analyses. CONCLUSIONS: In the NMA brodalumab, ixekizumab, risankizumab and guselkumab showed the highest levels of short-term efficacy. There were differences in efficacy between treatments within the same class. Longer-term analyses are needed to understand differences between these drugs beyond induction in what is a life-long condition.