Nordic Pharma (France)

BackgroundCurrent guidelines consider MTX as initial gold standard treatment for patients (pts) with RA. They also propose various strategies for MTX inadequate responders, among which the most frequent are optimization of MTX therapy (alone or in combination with csDMARDs or bDMARDs).ObjectivesThe objective of the trial was to explore the strategies applied in daily practice in RA pts with inadequate response to MTX.MethodsSTRATEGE was a prospective, observational, multicenter study. Main inclusion criteria were: confirmed RA (ACR 1987 or ACR/EULAR 2010 criteria) and treatment by MTX monotherapy with clinical, structural, functional and/or therapeutic evolution leading to therapeutic management modification. Data were obtained at 2 time-points: baseline and 6-month follow-up.ResultsBetween Sept 2014 and July 2015, 176 rheumatologists, at 90% with private practice, included 854 pts, 801 of which composed the analyzable baseline set. Pts baseline characteristics were [mean (SD)]: age: 57.4 (13.7) yrs; RA duration: 5.3 (6.7) yrs; DAS28: 4.0 (1.1), with the following distribution: <2.6 for 10%, >3.2 for 74% and >5.1 for 16%; HAQ: 1.1 (0.84); and extra-articular features and erosive disease for respectively 10.5% and 39.9% of pts. All pts were receiving MTX monotherapy, orally for 67.6% and at mean (SD) dose of 14.2 (4.1) mg/wk for oral and 16.6 (3.8) mg/wk for parenteral administration. Concomitant treatment included corticosteroids for 45.8% of pts, at a mean (SD) dose of 8.2 (6.3) mg/d, and folic acid for 90.0%. After the inclusion visit, MTX prescription has been identically maintained (dose and route) for 28.1% of pts, interrupted for 1.9% and modified for 70.0%. Changes included dose increasing for 50.2%, dose tapering for 1.8% and a route modification for 21.4% (88.2% oral -> parenteral). After inclusion visit, MTX oral versus (vs) parenteral balance was respectively 49.8% at mean (SD) dose 16.2 (4.0) mg/wk vs 45.8%, 18.0 (3.9) mg/wk. Biologic treatment was initiated for 14.6%, in association with MTX for 95.7%. Other csDMARD treatment was initiated for 1.2% in monotherapy and for 3.6% in association with MTX. The reasons for treatment modification were mainly active RA (72.0%), worsening of clinical and biologic parameters (31.4%), radiographic progression (14.5%), remission not achieved (12.4%), steroid dependence (11.3%), and MTX intolerance 5.0%. Six-month follow-up results show that all the active treatment strategies were significantly and equally successful in improving disease activity (Table).Table 1NDAS28 BaselineDAS28 (M6)D DAS28pMTX unchanged (Ref.)1263.4 (1.3)2.5 (1.0)*-0.8 (1.2)–MTX optimization5194.0 (1.0)2.9 (1.2)*-1.1 (1.3)0.10bDMARDs1174.6 (1.1)3.2 (1.1)*-1.4 (1.3)0.22csDMARDs394.3 (1.2)3.1 (1.3)*-1.3 (1.4)0.37Data presented: mean (SD). *p<0.0001 (M6 vs baseline), ANCOVA, adjusted for DAS28 at baseline.ConclusionsConsistently with all current guidelines, results of the large prospective observational study STRATEGE reveal an important place held by initial MTX treatment optimization before initiation of a biotherapy and emphasize the importance of treat-to-target strategy.Disclosure of InterestR.-M. Flipo Consultant for: Nordic Pharma, C. Gaujoux-Viala Consultant for: Nordic Pharma, C. Hudry Consultant for: Nordic Pharma, E. Zinovieva Employee of: Nordic Pharma, H. Herman-Demars Employee of: Nordic Pharma

IntroductionRheumatoid 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).MethodsThis 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).ResultsForty-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.ConclusionsThis 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.FundingNordic Group.Trial RegistrationEudraCT reference number: 2014-A0141245.

OBJECTIVE—The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen.RESEARCH DESIGN AND METHODS—In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference <0.4% between groups.RESULTS—A1C at 4 months was 8.1 ± 0.9 versus 8.0 ± 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI −0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (−0.4 ± 0.8 vs. −0.5 ± 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 ± 18 vs. 39 ± 20 units/day, P < 0.001), but aspart doses were higher (34 ± 17 vs. 26 ± 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 ± 0.8 vs. 8.0 ± 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 ± 0.9 vs. 7.6 ± 0.8%, P < 0.05) in association with decreased doses (P < 0.05).CONCLUSIONS—Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection.

A new type of Bragg-Fresnel multilayer lens (BFML) has been fabricated at IMT RAS and tested at LURE. The idea to combine different diffraction orders of a zone plate in one focal spot introduced by Simpson and Michette has been realized in a BFML with extended aperture. Matching of the two diffraction orders, the first and third, into one focal plane increases the output flux by a factor of two and the spatial resolution in the same order of magnitude.

This paper presents a new type of X-ray reflectometer that measures the grazing incidence reflectivity at an energy of 8 keV for angles from 0 - 2.5 degree(s) simultaneously. With an acquisition time of 5 s this allows to analyze the layer growth during a deposition process with a thickness accuracy in the sub-nm range. As a second independent method we are using kinetic and spectroscopic ellipsometry to follow the same deposition process.

In-line holography is attractive for x-ray microscopy due to its recording simplicity. A drawback of this method is the superposition of the virtual and real images, in which structures and details can be modified or lost. This superposition effectively limits the application of in-line holography to x-ray microscopy. We present in this work an iterative constrained algorithm for twin image elimination from Gabor holograms of finite support objects. It is based in the different spatial extent of both images, together with a finite support constraint. The conditions under which the algorithm is applicable are presented, together with an alternative Monte Carlo method for holograms of complex objects recorded in the shadow regions.