Evaluation of Usability and Acceptance of a New Autoinjector Intended for Methotrexate Subcutaneous Self-Administration in the Management of Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, for which the introduction of injectable treatments has had a major impact on quality of life directly related to the disease. The purpose of this descriptive study was to evaluate the usability of a new autoinjector, intended for methotrexate self-administration, based on the device's design and instructions for use (IFU). METHODS: This multicenter trial included three user groups: a group of patients with established RA subdivided into two groups according to their hand disability, and a group of caregivers or nurses. Each subject performed three simulated injections with a water-filled device on a foam pad. The first injection was made just after reading the IFU without further instructions (first phase). The second phase consisted of two injections made after explanations provided upon request of the subject in an optimum environment and in a "worst-case" home environment. The usability of the autoinjector was assessed by a questionnaire (success: ≥75% of positive responses) and by a score card reflecting injection performances (success: execution of ≥75% of handling steps). RESULTS: Forty-two subjects were enrolled in the study. During the first phase, the great majority of subjects succeeded in the usability questionnaire (90.5%) and in the injection performance (95.2%) with no major differences between the user groups. In the Second phase, all subjects from all three user groups succeeded in the usability questionnaire and had a positive rate of device handling, regardless of the environment and of the user group. No safety concerns were raised during the study. CONCLUSIONS: This study found a very high level of usability and subject acceptance of the autoinjector, intended for methotrexate self-administration, regardless of the hand disability and environmental conditions. FUNDING: Nordic Group. TRIAL REGISTRATION: EudraCT reference number: 2014-A0141245.

HTLV-1-associated arthropathy treated with anti-TNF-alpha agent.

Human T cell leukemia virus type 1 or HTLV-1 infection is a public health problem in endemic regions like Japan, Central America or Africa. Although the majority of HTLV-1 carriers remain asymptomatic throughout their lives, some patients could develop neurological disorder, inflammatory arthropathy also called HTLV-1-associated arthropathy or T-cell malignancy, the adult T-cell leukemia/lymphoma or ATL with a very poor prognosis. Described to be very close to rheumatoid arthritis, HTLV-1-associated arthropathy patients have few or no response to the first line therapy with corticosteroids and disease modifying antirheumatic drugs or DMARDs. The use of anti-TNF-α agents in these patients is an interesting alternative but asks the question of risk of developing an adult T-Cell leukemia/lymphoma. We reported an exceptional case of a smoldering ATL patient with an HTLV-1-associated arthropathy, refractory to corticosteroid, DMARDs and rituximab therapy, treated successfully with etanercept, without progression to aggressive ATL after 5 years.

Spinal imaging contributes to the diagnosis of Marfan syndrome.

UNLABELLED: The diagnosis of Marfan syndrome (MFS) is defined by a combination of major and minor criteria, related to the different systems involved, according to the Ghent nosology of the spine. Spinal imaging can detect both skeletal (including scoliosis and spondylolisthesis) and neurological involvement (i.e. dural ectasia). The aim of the present study was to assess the interest of screening the rachis by conventional radiography CR and complementary imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) in patients suspected of MFS, and to modelise the most relevant imaging procedure to diagnose MFS. METHODS: Evaluation of the sensitivity and specificity of CR of the lumbosacral spine versus sectional imaging for the detection of dural ectasia (DE) in a subgroup of 92 patients suspected of MFS. Retrospective analysis of the contribution of CR to the diagnosis of MFS in 1992 patients referred to our clinic. RESULTS: DE was detected by CR in 12 of the 92 patients (13%) and was always confirmed by CT or MRI. Complementary imaging alone detected 33 DE (35.9%). All patients with DE detected by CR were diagnosed with MFS. Among the 1992 patients, 591 were confirmed MFS; 117 patients had DE detected by CR (19,8%) while 12 (2,0%) were detected by complementary imaging. In MFS patients, 98 (16.6%) had significant scoliosis and 14 (2.4%) had spondylolisthesis. The positive predictive value of DE detected by CR for the diagnosis of MFS was 92.9% (95% IC: 86.8-96.4), and the negative predictive value was 74.6% (95% IC: 72.6-76.5). We conclude that spinal imaging is useful for the diagnosis of MFS.

Identification of the minimal combination of clinical features in probands for efficient mutation detection in the FBN1 gene.

Mutations identified in the fibrillin-1 (FBN1) gene have been associated with Marfan syndrome (MFS). Molecular analysis of the gene is classically performed in probands with MFS to offer diagnosis for at-risk relatives and in children highly suspected of MFS. However, FBN1 gene mutations are found in an ill-defined group of diseases termed 'type I fibrillinopathies', which are associated with an increased risk of aortic dilatation and dissection. Thus, there is growing awareness of the need to identify these non-MFS probands, for which FBN1 gene screening should be performed. To answer this need we compiled the molecular data obtained from the screening of the FBN1 gene in 586 probands, which had been addressed to our laboratory for molecular diagnosis. In this group, the efficacy of FBN1 gene screening was high in classical MFS probands (72.5%,), low (58%) in those referred for incomplete MFS and only slight (14.3%) for patients referred as possible MFS. Using recursive partitioning, we found that the best predictor of the identification of a mutation in the FBN1 gene was the presence of features in at least three organ systems, combining one major, and various minor criteria. We also show that our original recommendation of two systems involved with at least one with major criterion represents the minimal criteria because in probands not meeting these criteria, the yield of mutation identification drastically falls. This recommendation should help clinicians and biologists in identifying probands with a high probability of carrying a FBN1 gene mutation, and thus optimize biological resources.

Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders.

TGFBR1 and TGFBR2 gene mutations have been associated with Marfan syndrome types 1 and 2, Loeys-Dietz syndrome and isolated familial thoracic aortic aneurysms or dissection. In order to investigate the molecular and clinical spectrum of TGFBR2 mutations we screened the gene in 457 probands suspected of being affected with Marfan syndrome or related disorders that had been referred to our laboratory for molecular diagnosis. We identified and report 23 mutations and 20 polymorphisms. Subsequently, we screened the TGFBR1 gene in the first 74 patients for whom no defect had been found, and identified 6 novel mutations and 12 polymorphisms. Mutation-carrying probands displayed at referral a large clinical spectrum ranging from the Loeys-Dietz syndrome and neonatal Marfan syndrome to isolated aortic aneurysm. Furthermore, a TGFBR1 gene mutation was found in a Shprintzen-Goldberg syndrome patient. Finally, we observed that the yield of mutation detection within the two genes was very low : 4.8% for classical MFS, 4.6% for incomplete MFS and 1% for TAAD in the TGFBR2 gene; 6.2%, 6.2% and 7% respectively in the TGFBR1 gene; in contrast to LDS, where the yield was exceptionally high (87.5%).

Bone mineral density in Marfan syndrome. A large case-control study.

OBJECTIVE: To measure bone mineral density (BMD) in a group of patients meeting Gand criteria for Marfan syndrome, comparatively with a group of healthy controls. METHODS: Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD at the hip and wrist in 130 patients seen at the Multidisciplinary Marfan Clinic, Paris, France. Results were compared to values in the database of the absorptiometry machine (Hologic QDR100) and to values in 72 healthy height-matched controls including 35 whose body mass index (BMI) values were similar to those in the patients. RESULTS: A history of fractures was noted in 32 (24.6%) patients. Z-score values were significantly decreased in the patients compared to the Hologic database values at the femoral neck (-1.190+/-0.098, P<0.0001) and wrist (-1.403+/-1.06; P < 0.001). Patients had significantly lower BMD values at the femoral neck compared to the height-matched controls (0.841+/-0.15 versus 1.010+/-0.017; P<0.0001). BMD values were also significantly lower in the patients compared to the controls of similar height and BMI. BMD values did not correlate with history of fractures or acetabular protrusion. In the patients, BMD values lower than -2.5 correlated with presence of dural ectasia. CONCLUSION: Men and women with Marfan syndrome have significant osteopenia independent from BMI.