Depletion-restitution therapy for autoimmune rheumatic diseases. Part 1. Fundamental prerequisites and efficacy of modern treatment technologies: anti-B-cell drugs and CAR-T therapy

Modern Rheumatology Journal, Journal Year: 2025, Volume and Issue: 19(2), P. 7 - 17

Published: April 22, 2025

The key element in the pathogenesis of systemic autoimmune rheumatic diseases is breakdown immunological tolerance and formation a pool autoreactive cells. This leads to uncontrolled activation effector arm cellular (T-lymphocytes) humoral (B-lymphocytes plasma cells) immunity, proliferation clones, persistence memory In this process, T-cells, B-cells, cells memory, interaction with complex pathogenic signals from microenvironment, ensure stability adaptability developing inflammatory process. modern clinical practice, prevailing approach prescribing medications "therapeutic pyramid" strategy, which involves gradual escalation treatment until remission achieved. does not address mechanisms and, as result, requires lifelong therapy associated numerous adverse effects. term “depletion-restitution therapy” proposed (from English “depletion” – exhaustion; Latin “restitutio ad integrum” restoration original state, complete recovery) describe an alternative approach. characterized by methods based on massive, shortterm cytotoxic impact, leading profound reduction followed repopulation "naive" elements. Consequently, restores enables ultra-long, drug-free remissions. Currently, principles depletion-restitution have already been integrated into oncology, hematology, neurology. Among most promising potential targets for such rheumatology are effectors immune system: plasmablasts, At present stage, implementing CAR-T therapeutic bispecific monoclonal antibodies.

Language: Английский

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Interstitial lung diseases and autoimmunity

Rheumatology Science and Practice, Journal Year: 2025, Volume and Issue: 63(2), P. 119 - 128

Published: May 1, 2025

Lung disease is one of the most common manifestations systemic autoimmune rheumatic diseases (SARDs), involving all parts respiratory system in pathological process. Interstitial lung (ILD) are great importance and often lead to development progressive pulmonary fibrosis (PPF). The following clinical categories patients distinguished within ILDs associated with SARDs (ILD-SARDs): ILD a reliable diagnosis SARDs; as first manifestation or interstitial pneumonia features. Clinical phenotypes ILD-SARDs vary from «asymptomatic» «rapidly progressing» related risk factors for damage. These should be considered conducting clinical, laboratory instrumental screening prescribing anti-inflammatory antifibrotic therapy. In pulmonology practice patient may have previously established SARDs, this could suspected based on number symptoms diseases. Problem diagnostic very complex, which determines multidisciplinary approach interaction rheumatologists, pulmonologists radiologists. possibilities perspectives pharmacotherapy rational use anti-inflammatory, immunomodulatory drugs. issues emphasized: identification rapidly progressing phenotype fibrosis; contribution inflammatory activity; effectiveness therapy relation leading “extrapulmonary” pneumotoxicity implementation “treat target” concept. greatest achievement chimeric antigen receptor (CAR) T-cell therapy, mechanism elimination pathogenic autoreactive B-cells. Preliminary data CAR indicate high efficacy wide range including progression sclerosis antisynthetase syndrome, there strong evidence important role mechanisms pathogenesis ILD.

Language: Английский

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Colchicine: Repositioning an “ancient” medicine in the 21st century

Rheumatology Science and Practice, Journal Year: 2024, Volume and Issue: 62(5), P. 445 - 464

Published: Oct. 31, 2024

The main indications for colchicine treatment until recently were gout, pericarditis, familial Mediterranean fever and some other auto-inflammatory diseases. expansion of (repositioning) the use in direction prevention cardiovascular complications should be considered as one major events medicine XXI century. Deciphering role inflammation most important mechanism development atherosclerosis has created prerequisites concept anti-inflammatory therapy atherosclerosis, which low-dose can take an place, complementing effects aspirin, statins antihypertensive therapy. analysis materials from randomized placebo-controlled studies indicates a decrease frequency patients with coronary heart disease (by 31%) who have suffered myocardial infarction 23%), well 33%), stroke, need revascularization mortality. low dose (0.5 mg/day) is approved by U.S. Food Drug Administration disease. It assumed that future will place pathology associated atherosclerotic vascular

Language: Английский

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Experience with olokizumab in the treatment of polymyalgia rheumatica and giant cell arteritis: A series of cases

Rheumatology Science and Practice, Journal Year: 2024, Volume and Issue: 62(4), P. 431 - 434

Published: Sept. 3, 2024

Glucocorticoids are the basis for treatment of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), however, their long-term use is associated with a number well-known side effects. Despite fact that significant patients these diseases require treatment, approaches to therapy remain insufficiently developed. The role traditional anti-inflammatory drugs remains uncertain due insufficient efficacy inconclusive evidence base. A possible solution this problem biological agents, in particular, affecting interleukin (IL-6) axis. This series clinical observations presents experience using IL-6 inhibitor olokizumab GCA PMR. data obtained consistent positive international group demonstrate both efficiency disease activity control pronounced steroid-sparring effect. Olokizumab promising drug

Language: Английский

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