The first two authors contributed equally to this study Most autoinflammatory disorders typically come out in the pediatric population, although a limited number of patients may experience disease onset during adulthood. To date, a late disease onset has been described only in familial Mediterranean fever, caused by mutations in the MEFV gene, and in tumor necrosis factor receptor-associated periodic syndrome, caused by mutations in the TNFRSFIA gene. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that mutations will be found in an even smaller percentage of cases. With the aim of improving the genetic diagnosis in adults with suspected autoinflammatory disorders, we recently identified a set of variables related to the probability of detecting gene mutations in MEFVand TNFRSFIA and, in addition, we have also proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. In the present study we evaluated the preliminary score sensitivity and specificity on a wider number of patients in order to validate the goodness of fit ofthe model. Two hundred and nineteen consecutive patients with a clinical history of periodic fever attacks were screened for mutations in MEFV

Rheumatoid arthritis (RA), with a prevalence of 0.46%, is found in about 272,004 patients in Italy. The socioeconomic cost of rheumatoid arthritis in Italy in 2002 has been estimated at Euro 1,600 million. Cost-effectiveness evaluations have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. Many cost-effective studies have been based on the variation of Health Assessment Questionnaire (HAQ) in clinical trials. The objective of this study is to perform a cost-effective analysis of 86 patients with rheumatoid arthritis in therapy with adalimumab 40 mg every other week and etanercept 50 mg/week for two years in a population of patients observed in clinical practice. The group of patients in therapy with adalimumab had also taken methotrexate, mean dose 12.4+/-2.5 mg/week (22 patients) or leflunomide 20 mg/day (16 patients). The group of patients in therapy with etanercept had also taken methotrexate, mean dose 11.7+/-2.6 mg/week (24 patients) or leflunomide 20 mg/day (24 patients). Incremental costs and QALYs (quality adjusted life years) gains are calculated compared with baseline, assuming that without biologic treatment patients would remain at the baseline level through the year. Conversion HAQ scores to utility were based on the Bansback algorithm. The results after two years showed: in the group methotrexate+adalimumab the QALY gained was 0.62+/-0.15 with a treatment cost of Euro 26,517.62 and a QALY/cost of Euro 42,521.13. In the group methotrexate + etanercept the QALY gained was 0.64+/-0.26 with a treatment cost of Euro 25,020.96 and a QALY/cost of Euro 39,171.76. The result of using etanercept in association with methotrexate is cost-effectiveness with a QALY gained under the acceptable threshold of Euro 50,000. These are important data for discussion from an economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice.

Although idiopathic recurrent acute pericarditis (IRAP) is generally presumed to derive from an autoimmune process, increasing interest is currently being devoted to autoinflammatory diseases, a group of disorders of the innate immune system caused by mutations of genes involved in the regulation or activation of the inflammatory response, without any apparent involvement of autoimmunity. The tumour necrosis factor receptor-1-associated periodic syndrome is the most common autosomal dominant autoinflammatory disorder and is caused by mutations in the TNFRSF1A gene encoding the 55-kD receptor for tumour necrosis factor-α. IRAP patients carrying TNFRSF1A gene mutations have been recently described. We report herein the first IRAP patients carrying the rare R104Q and D12E TNFRSF1A gene mutations, thus expanding the spectrum of tumour necrosis factor receptor-1-associated periodic syndrome mutations in IRAP patients.

The primary aim of the study was to evaluate the long-term effectiveness of adalimumab (ADA) in a cohort of non-radiographic axial spondyloarthritis (nr-axSpA), and the secondary aims were to identify predictive factors of response and evaluate radiological progression.We evaluated 37 patients (male/female: 12/25; mean age 49 ± 14; mean disease duration: 6.3 ± 5.8) with active nr-axSpA (Assessment of SpondyloArthritis International Society criteria), despite the treatment with ≥1 nonsteroidal anti-inflammatory drug for at least 3 months, initiating the treatment with ADA 40 mg every other week. Patients were treated for 24 months, and evaluated at baseline, 6, 12, and 24 months. Outcome measures included Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index. Radiograph of the spine and sacroiliac joints and magnetic resonance of the sacroiliac joints were performed at baseline and according to the standard of assessment for the disease.The proportion of patients that achieved a BASDAI50 response at 6, 12 and 24 months was 51.3%, 70.3%, and 76.8%, respectively. Treatment was well tolerated with no unexpected adverse events and/or serious adverse events. All patients remained on treatment for 2 years, with a good compliance. We did not identify any predictive factor of response to therapy. Moreover, modified Stoke Ankylosing Spondylitis Spine Score and Spondyloarthritis Research Consortium of Canada scores showed a trend of improvement during the study period.ADA was effective on clinical and radiological outcomes at 2-year follow-up; thus, early treatment with ADA may prevent radiographic damage and be associated with low disease activity or remission. Moreover, data from this cohort study have confirmed safety and tolerability profile of ADA in nr-axSpA in the long term.