How should a patient with rheumatoid arthritis behave after achievement of remission?

The paper considers the very urgent problem of optimization of the management of rheumatoid arthritis (RA) patients who have achieved remission (or persistent low disease activity) during therapy using biologicals. It analyzes the results of BeSt, OPTIMA, HIT HARD, ACT-RAY, AVERT, PRESERVE, RETRO, PRIZE, DRESS, HOPEFUL-2, and HONOR studies, the data of NinJa and CORRONA registries, and the experience gained in treating psoriasis concerning practically important issues, such as whether tumor necrosis factor-α inhibitors and biologicals with other mechanisms of action can be discontinued; whether the whole anti-inflammatory therapy can be stopped; whether the dose of biologicals can be reduced as an alternative to complete discontinuation or as a step to discontinue biologicals; whether repeated or intermittent therapy with biologicals can be used; what value of the depth of suppression of inflammatory activity is in solving the problem of whether biologicals can be discontinued. The current results may lead to the conclusion that in RA the dose of biologicals may be successfully reduced and, in some cases, the latter may be completely discontinued. This possibility seems to be associated with the depth of remission. Repeated use of biologicals generally gives rise to prompt improvement in patients with a recurrent disease-activity rebound. The results of a trial of etanercept are most optimistic. Re-treatment with biologicals generally provides fast improvement in patients with a relapse of disease activity. The results of the trials of etanercept are most optimistic

Fermion conformal bootstrap in 4d

We apply numerical conformal bootstrap techniques to the four-point function of a Weyl spinor in 4d non-supersymmetric CFTs. We find universal bounds on operator dimensions and OPE coefficients, including bounds on operators in mixed symmetry representations of the Lorentz group, which were inaccessible in previous bootstrap studies. We find discontinuities in some of the bounds on operator dimensions, and we show that they arise due to a generic yet previously unobserved fake primary effect, which is related to the existence of poles in conformal blocks. We show that this effect is also responsible for similar discontinuities found in four-fermion bootstrap in 3d, as well as in the mixed-correlator analysis of the 3d Ising CFT. As an important byproduct of our work, we develop a practical technology for numerical approximation of general 4d conformal blocks

Как вести больного ревматоидным артритом после достижения ремиссии?

The paper considers the very urgent problem of optimization of the management of rheumatoid arthritis (RA) patients who have achieved remission (or persistent low disease activity) during therapy using biologicals. It analyzes the results of BeSt, OPTIMA, HIT HARD, ACT-RAY, AVERT, PRESERVE, RETRO, PRIZE, DRESS, HOPEFUL-2, and HONOR studies, the data of NinJa and CORRONA registries, and the experience gained in treating psoriasis concerning practically important issues, such as whether tumor necrosis factor-α inhibitors and biologicals with other mechanisms of action can be discontinued; whether the whole anti-inflammatory therapy can be stopped; whether the dose of biologicals can be reduced as an alternative to complete discontinuation or as a step to discontinue biologicals; whether repeated or intermittent therapy with biologicals can be used; what value of the depth of suppression of inflammatory activity is in solving the problem of whether biologicals can be discontinued. The current results may lead to the conclusion that in RA the dose of biologicals may be successfully reduced and, in some cases, the latter may be completely discontinued. This possibility seems to be associated with the depth of remission. Repeated use of biologicals generally gives rise to prompt improvement in patients with a recurrent disease-activity rebound. The results of a trial of etanercept are most optimistic. Re-treatment with biologicals generally provides fast improvement in patients with a relapse of disease activity. The results of the trials of etanercept are most optimistic.В статье рассматривается весьма актуальная проблема оптимизации ведения больных ревматоидным артритом (РА), достигших состояния ремиссии (или стойко низкой активности болезни) на фоне терапии с применением генно-инженерных биологических препаратов (ГИБП). Проанализированы результаты исследований BeSt, OPTIMA, HIT HARD, ACT-RAY, AVERT, PRESERVE, RETRO, PRIZE, DRESS, HOPEFUL-2, HONOR, данные регистров NinJa и CORRONA, а также опыт, полученный при лечении псориаза, в отношении таких важных в практическом плане вопросов, как: возможность отмены ингибиторов фактора некроза опухоли α и ГИБП с иными механизмами действия, возможность отмены всей противовоспалительной терапии, снижение дозы ГИБП как альтернатива полной отмене или ступень на пути к отмене ГИБП, повторное назначение и «прерывистое лечение» ГИБП, значение глубины подавления воспалительной активности для решения вопроса о возможности отмены ГИБП. На основе полученных к настоящему времени результатов можно заключить, что при РА вероятно успешное снижение дозы, а в некоторых случаях – и полная отмена ГИБП. Такая возможность, по-видимому, связана с глубиной ремиссии. У пациентов с рецидивом активности болезни повторное назначение ГИБП, как правило, приводит к быстрому улучшению. Наиболее оптимистичными выглядят результаты исследований этанерцепта

Efficiency of teaching patients with early-stage rheumatoid arthritis

Education programs are an important part of the management of patients with rheumatoid arthritis (RA).Objective: to develop a unified model of an education program for RA patients and to evaluate its efficiency at the early stage of the disease.Material and methods. A group education program was worked out with the support of the All-Russian public organization of the disabled “The Russian rheumatology organization “Nadezhda” (Hope)” and encompassed 4 daily classes lasting 90 min. All information was presented by a multidisciplinary team of specialists (rheumatologists, a cardiologist, a psychologist, a physiotherapist, and a physical trainer). The study included 55 patients with early RA (89.1% of women aged 18 to 62 years; the duration of the disease was 2 to 22 months); of them 25 were taught using the education program (a study group); 30 received drug therapy only (a control group). Following 3 and 6 months, the number of tender and swollen joints, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and pain were determined applying a 100-ml VAS, DAS28, HAQ, and RAPID3. Adherence to non-drug treatments was assessed employing a special patient questionnaire.Results. Three and six months after being taught, two patient groups showed increases in adherence to joint protection methods by 13 and 10 times (p<0.01), regular physical training by 4 and 3.25 times (p<0.01), uses of orthoses for the wrist joint by 2 times and 75% (p<0.01) and knee orthoses by 33.3 and 50.0% (p<0.01), and orthopedic insoles by 71.4 and 57.1% (p<0.01), respectively. Following 6 months, there were statistically significant differences between the two groups in most parameters (p<0.05), except for ESR, CRP, and DAS28 (p>0.05). Further more, a good response to treatment was significantly more common in these periods, as shown by the EULAR response criteria (DAS28): 56.3% versus 40% in the control group (p<0.05).Conclusion. The education program decreases the intensity of pain syndrome and improves the functional status and quality of life of patients with early RA within 6 months. Patient education enhances adherence to non-drug treatments. The highest positive result was achieved just 3 months later; it slightly tailed off at 6 months. This necessitates re-education in succeeding 3–6 months

Голимумаб в лечении воспалительных заболеваний: роль иммуногенности

The review considers the specific features of golimumab (GLM), a representative of a group of tumor necrosis factor-α inhibitors primarily by comparing its immunogenicity parameters with other drugs in this group (infliximab, adalimumab, certolizumab pegol, etanercept). Despite its fundamental similarity with other biologicals from a category of monoclonal antibodies, GLM is shown to be characterized by a significantly lower detection rate for antibodies to the drug and by its high serum concentration stabilities and a sustained clinical response.В обзоре рассматриваются особенности голимумаба (ГЛМ), представителя группы ингибиторов фактора некроза опухоли α, в первую очередь с точки зрения сравнения показателей иммуногенности с другими препаратами этой группы (инфликсимаб, адалимумаб, цертолизумаба пэгол, этанерцепт). Показано, что ГЛМ, несмотря на принципиальное сходство с другими генно-инженерными биологическими препаратами из категории моноклональных антител, характеризуется значительно меньшей частотой обнаружения антител к препарату, высокой стойкостью сывороточной концентрации и высокой стабильностью достигнутого уровня клинического ответа

Острые вопросы стратегии лечения ревматоидного артрита

The current treatment strategy for rheumatoid arthritis (RA) is based on the principles of early aggressive therapy and tight control, which are summarized in «Treat-to-Target» recommendations. The draft RA treatment guidelines by the Association of Rheumatologists of Russia (ARR) reflect these principles in expanded form. Twenty-four ARR recommendations contain the detailed description of current treatments for RA, which relies on the principles of evidence-based medicine. Some practical issues for the management of patients with RA require special attention. The comparison of a number of randomized trials and the author’s experience in the REMARCA study may conclude that subcutaneous methotrexate (MTX) in an initial dose 10–15 mg/week with its fast increase up to 20Р30 mg/week is an optimal first-line therapy for RA. To choose the period within which a decision should be made on the incorporation of biologic agents (BA) in patients with an inadequate response to MTX is a serious matter. The experience gained in a number of clinical trials, particularly in those of etanercept, shows that a 12-week follow-up is sufficient in most patients. First of all, it is important for early RA. After achieving sustained remission, the reasonable tactics is to accurately reduce the dose of a BA although there may also be complete therapy discontinuation («treatment holiday») in the future.Современная стратегия лечения ревматоидного артрита (РА) основана на принципах ранней агрессивной терапии и тщательного контроля, которые суммированы в рекомендациях «Лечение до достижения цели». Эти принципы в развернутой форме отражены в проекте Рекомендаций по лечению РА Ассоциации ревматологов России (АРР). 24 рекомендации АРР представляет собой подробное изложение современных методов терапии РА, основанное на принципах доказательной медицины. Особого внимания требуют некоторые практические вопросы ведения больных РА. Сопоставление ряда рандомизированных исследований и собственного опыта в исследовании РЕМАРКА позволяют заключить, что назначение подкожной формы метотрексата (МТ) в начальной дозе 10–15 мг/нед с быстрым ее повышением до 20–30 мг/нед является оптимальным методом первой линии терапии РА. Серьезным вопросом является выбор периода, в течение которого необходимо принимать решение о подключении генно-инженерных биологических препаратов (ГИБП) при недостаточном ответе на МТ. Опыт, полученный в ряде клинических исследований, особенно в исследованиях этанерцепта, показывает, что для большинства пациентов достаточно 12 нед наблюдения. В первую очередь это важно при раннем РА. После достижения стойкой ремиссии разумной тактикой будет аккуратное снижение дозы ГИБП, хотя в перспективе возможна и полная отмена терапии («treatment holiday»).