CHANGES OF CLINICAL AND RADIOGRAPHIC PARAMETERS DURING DENOSUMAB THERAPY IN RHEUMATOID ARTHRITIS PATIENTS RECEIVING GLUCOCORTICOIDS: PRELIMINARY RESULTS

When treating rheumatoid arthritis (RA), it is important not only to suppress inflammation, but also to prevent local and generalized bone loss, particularly in patients receiving glucocorticoids (GC). Denosumab is a fully human monoclonal antibody that binds receptor activator of nuclear factor kappa B ligand (RANKL), prevents its interaction with receptor on osteoclasts, reduces their activity, and inhibits bone resorption.Objective: to evaluate the effect of 12-month therapy with denosumab on bone mineral density (BMD) of the axialand peripheral skeleton and destructive changes in the hand and foot joints of RA patients receiving GC.Subjects and methods. Fifty-two postmenopausal women with RA concurrent with osteoporosis received subcutaneous denosumab 60 mg twice: at baseline and 6 months later. BMD was measured before drug administration and after 12 months of a follow-up, by applying dual-energy X-ray absorptiometry of three sections: the lumbar spine (LI–IV), femoral neck (FN), and distal forearm (DF). Radiographic changes in the hand and foot joints were assessed using the Sharp method modified by van der Heijde (SVH) at baseline and 12 months later.Results and discussion. The patients’ mean age was 58.4±6.4 years; the mean RA duration – 19.0±10.9 years. Antiinflammatorytherapy was performed in all the patients, including 30 (57.7%) who received GC. The mean BMD during follow-up increased from 0.814±0.101 to 0.848±0.103 g/cm2 in LI–IV (p<0.001), from 0.629±0.089 to 0.641±0.090 g/cm2 in FN (p=0.02), and from 0.497±0.094 to 0.502±0.091 g/cm2 in DF (р=0.34). The patients receiving and not  receiving GC showed a significant increase in LI–IV BMD and a tendency for its rise in FN and DF. There was a significant increase of X-ray changes in the hand and foot joints. Seven of the 52 patients were found to have a larger number of erosions: 33.0 [4.0; 78.0] at baseline and 39.0 [5.0; 90.0] after 12 months (p=0.017); 5 patients had a larger number of narrowed joint spaces: 119.0 [18.0; 140.0] and 124.0 [20.0; 146.0] (р=0.043); the total SVH score increased in 8 patients: 175.5 [54.0; 221.5] and 182.0 [57.0; 235.0] (р=0.011), respectively. Moreover, dividing the patients into groups according to the use of GC revealed significant increase of the number of erosions and total SVH scores only in the patients receiving GC.Conclusion. Therapy with subcutaneous denosumab 60 mg twice a year at a 6-month interval could significantly increase LI–IV BMD regardless of GC intake. Progression of radiographic joint changes was noted mainly in patients receiving G

ФОТОЭЛЕКТРОННЫЕ УМНОЖИТЕЛИ С МНОГОСЛОЙНЫМИ ПЛЕНОЧНЫМИ ЭКРАНАМИ ДЛЯ ЗАЩИТЫ ОТ ВОЗДЕЙСТВИЯ ВНЕШНИХ ПОСТОЯННЫХ МАГНИТНЫХ ПОЛЕЙ

The effectiveness of the screening constant magnetic field is multi-layered film screens system of NiFe/Cu, formed on the cylindrical housing of photomultiplier tubes, and compared with screen-based steel material – brand 80NHS permalloy. It is shown that the most effective is the screen on the basis of the multilayered film screens, which provide shielding effectiveness value 8–10 in magnetic fields with induction of 0,1–1 mT, and 80–100 – in magnetic fields with induction of 2–4 mT , which is 4–5 times higher than for the screen of the material 80NHS.Изучена эффективность экранирования постоянного магнитного поля многослойными пленочными экранами системы NiFe/Cu, сформированными на цилиндрических корпусах фотоэлектронных умножителей, и проведено сопоставление с экраном на основе металлургического материала – пермаллой марки 80НХС. Показано, что наиболее эффективным является экран на основе многослойных пленочных структур, который обеспечивает значения эффективности экранирования 8–10 в магнитных полях с индукцией 0,1–1 мТл, и 80–100 – в магнитных полях с индукцией 2–4 мТл, что в 4–5 раз выше, чем для экрана из материала 80НХС

APPLICATION OF MULTILAYER FILM CONFIGURATION TO PROTECT PHOTOMULTIPLIER AGAINST EXTERNAL STATIC MAGNETIC FIELDS

The effectiveness of the screening constant magnetic field is multi-layered film screens system of NiFe/Cu, formed on the cylindrical housing of photomultiplier tubes, and compared with screen-based steel material – brand 80NHS permalloy. It is shown that the most effective is the screen on the basis of the multilayered film screens, which provide shielding effectiveness value 8–10 in magnetic fields with induction of 0,1–1 mT, and 80–100 – in magnetic fields with induction of 2–4 mT , which is 4–5 times higher than for the screen of the material 80NHS

The impact of permanent magnetic fields on photomultiplier HAMAMATSU R7899-20 used in a hadron calorimeter of LHCb experiment

The influence of a permanent magnetic field strength up to 40 Gs (4 mT) to operation PMT HAMAMATSU R7899-20 with its standart magnetic screens and without them is investigated. This PMT is used in a hadron calorimeter of LHCb experiment at CERN. It is shown that the use of a protective housing made of steel in joint its use with permalloy screen significantly reduces screening efficiency. It proposed to use a protective housing made from non-magnetic material (duralumin) electrolytic coated with a multilayered film as magnetic shield. This solution can be used in a hadron calorimeter, the CERN installations SHiP

Characteristics of magnetic shields for protection PMT in the LHCb hadron calorimeter

CERN is preparing the new experiment aimed at the detection of weakly interacting massive long-lived particles. The experiment was called SHiP. The instrumental and technological solutions successfully used in experimental setups ATLAS, LHCb and others will be applied in experimental setup SHiP. One of these units is a hadrons calorimeter. It uses several thousands photomultiplier tubes (PMT) placed in protective magnetic shields because PMTs are located near strong permanent magnets. Taking into account that since the creation of the experimental setup LHCb has been passed more than 10 years and there are new manufacturing techniques of magnetic screens appeared, we investigate the characteristics of shielding screens used in the LHCb, and proposed the recommendations to magnetic screens’ designs for SHiP experiment

The first Russian strategic study of pharmacotherapy for rheumatoid arthritis (REMARCA)

The international recommendations «Treat to target» (T2T) underline the greatest importance of treatment strategy for the success of treating rheumatoid arthritis (RA). Evaluation of the efficiency of this approach obviously requires special strategic studies with an adaptive design, which substantially differ from classical randomized clinical trials and are much closer to clinical practice. To date, there are only single publications on the practical application of the T2T recommendations, there is a problem in the choice of effectiveness criteria and there are a number of other important problems associated with the introduction of these recommendations. The Russian study REMARCA is to answer these questions. Its design focuses on the practical adaptation of the T2T strategy to treat patients with earlyand extended-stage active RA who have poor prognostic factors, by using subcutaneous methotrexate and genetically engineered biological agents (GEBA). Preliminary analysis shows that therapy according to the REMARCA protocol is successful in the majority of patients. The high rate of low RA activity and remission has been achieved during subcutaneous methotrexate monotherapy. The patients who need GEBA to be incorporated may be initially more resistant to therapy. The patients with early RA have better chances of successful T2T therapy than those with extended-stage RA

THE FIRST RUSSIAN STRATEGIC STUDY OF PHARMACOTHERAPY FOR RHEUMATOID ARTHRITIS (REMARCA TRIAL): RESULTS OF 12-MONTH TREATMENT IN 130 PATIENTS

To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilities of its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care.Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT) and biological agents (BA) when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA) who have risk factors for a poor prognosis.Subjects and methods.The results of the REMARCA (Russian InvEstigation of MethotrexAte and biologicals in eaRly aCtive inflammatory Arthritis) trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%); anti-cyclic citrullinated peptide antibody positivity (89.2%). Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months)); 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months)). In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission) was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA) (a tumor necrosis factor inhibitor or abatacept). If the former was insufficiently effective, it was substituted for a BA from another class.Results. Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7%) patients; a BA was given to 81 (62.3%) patients. Following 6 and 12 months, low activity or remission according to SDAI was observed significantly more frequently in the patients who continued subcutaneous MT monotherapy than in those who received combined therapy with MT and BA. The similar results were obtained by using DAS28 and CDAI to assess a trend in disease activity. After 6- and 12-month follow-up, there was a significantly more marked decline of tender joint count, SDAI and CDAI in early RA than in advanced-stage RA; at 12 months, SDAI remission rate was 45.7% and 28.3%, respectively (p=0.047).Conclusion. The treat-to-target strategy should be used in real clinical practice and can yield spectacular results. Active therapy with subcutaneous MT with its rapid dose escalation to the maximally tolerable dose allows identification of a considerable group of patients (38%) with a good response to MT monotherap