ABSTRACT
INTRODUCTION: Deficiencies in interleukin (IL)-1 receptor (IL-R) antagonist (DIRA) and IL-36R antagonist (DITRA) are rare genetic autoinflammatory diseases related to alterations in antagonists of the IL-1 pathway. IL-1 antagonists may represent therapeutic alternatives. Here, we aim to provide a scoping review of knowledge on use of IL-1-targeting drugs in DIRA and DITRA. METHODS: An a priori protocol was published, and the study was conducted using the methodology described in the Joanna Briggs Institute Reviewer's Manual and the recently published PRISMA Extension for Scoping Review statement. A three-step search using MEDLINE and EMBASE databases until March 2018 with additional hand searching was performed. Data charting was performed. The search, article selection, and data extraction were carried out by two researchers independently. RESULTS: Twenty-four studies on use of anti-IL-1 drugs were included [15 studies including patients with diagnosis of DIRA (n = 19) and 9 studies including patients with diagnosis of DITRA (n = 9)]. Most studies followed a multicenter observational design. Among all patients who received treatment with anti-IL-1 drugs, nine and four mutations in IL1RN and IL36RN were found, respectively. Patients with DIRA were treated with anakinra (n = 17), canakinumab (n = 2), or rinolacept (n = 6). All patients with DITRA were treated with anakinra, and only one case was also treated with canakinumab. Time-to-response frequencies were evaluated as immediate, short, and medium-long term for DIRA (17/17, 15/17, and 9/10, respectively) and DITRA (7/9, 3/9, and 2/9, respectively). Most DITRA patients in whom anti-IL-1 treatment failed experienced good response to anti-tumor necrosis factor alpha or anti-IL-12/23 drugs. The safety profiles of treatments were similar in both diseases. CONCLUSIONS: Evidence on use of anti-IL-1 drugs in DIRA and DITRA is scarce and based on observational studies. Larger studies with better methodological quality are needed to increase confidence in use of these drugs in patients with DIRA and DITRA.
ABSTRACT
INTRODUCTION: The interleukin (IL)-1 pathway has been identified as being involved in inflammatory and neoplastic skin diseases such as psoriasis, atopic dermatitis, neutrophilic dermatosis, melanoma, and squamous cell carcinoma. Drugs developed to target the IL-1 pathway are currently used to treat these pathologies, and although they are becoming more selective, they are not exempt from adverse events and high costs. Integrating the best research evidence with clinical experience and patient needs has been shown to improve care, health, and cost outcomes. This is because evidence-based guidelines rank interventions according to cost-effectiveness. However, evidence on this topic is scarce for several reasons. First, although randomized clinical trials currently provide the best evidence, they are not always available. Second, there are no secondary scientific studies that summarize the use of IL-1-targeting agents in dermatology. We therefore sought to develop an a priori protocol for broadly reviewing the available evidence on the use of IL-1-targeting drugs in the treatment of dermatological diseases. METHODS: We used the latest methodology to perform a scoping review as described in the Joanna Briggs Institute manual. RESULTS/DISCUSSION: Developing and applying a methodology for evidence synthesis promotes reproducibility and increases the validity of secondary scientific investigations, making it the optimal strategy for scientifically synthesizing a broad field such as the indications for and the mechanisms of action, efficacies, safety, and costs of IL-1-targeting drugs in the treatment of dermatological diseases. Quantitative synthesis facilitates the detection of knowledge gaps and the identification of new questions that can be addressed through systematic reviews. We present an a priori protocol for exploring the available evidence on this topic.
ABSTRACT
Incidence of colorectal cancer has steadily increased in both the sexes and across all age groups during the last decades in Spain, in contrast with other countries where incidence decreased during this period. This increase is more marked among men, probably due to a high exposure to risk factors such as smoking, heavy drinking, overweight and diabetes. Annual age-adjusted mortality rates have increased in Spain during the period 1951-2000, but from that time until 2006 these rates have kept steady in males and fallen in females. When analyzing the evolution of exposure to behavioural factors during this period, known as risk or protective factors for colorectal cancer in Spain, notorious increases in tobacco and alcohol consumption, red and processed meats intake and a decreased ingestion of vegetables, cereals and beans were observed. Cigarette smoking, alcohol consumption, red meats, poultry, fish, vegetables and fruit were highly, positively correlated with colorectal cancer incidence and mortality, and cereals and beans consumption showed strong, negative correlations. At the same time and during this period, physical exercise decreased and overweight, obesity and diabetes mellitus notably increased. Certain changes in diet and lifestyle can be attributed to the growth in income during the last decades, but the lack and delay in implementing legislative and educational measures by the State and Regional Governments during decades cannot be ignored. In colorectal cancer, a minimal time span of 10-15 years is necessary for changes in exposure to risk factors to be able to modify the incidence of the tumour. Therefore, the implementation of more vigorous legislative and educational measures in Spain against smoking, heavy drinking, red meat intake, sedentary lifestyle, overweight and others reviewed in this study, is urgent.
