Central sensitization (CS) is a condition characterised by (associated with) neuroplastic changes in nociceptive neurons, sub-threshold afferent input, pain hypersensitivity and development widespread pain. Insufficient response to disease-modifying antirheumatic drugs (DMARDs) can be caused by CS.Objective – to evaluate the features of clinical manifestations of RA in patients with ineffective antirheumatic therapy, depending on the presence of signs of CS.Material and methods. The study group included 509 patients diagnosed with RA (according to ACR/EULAR classification criteria, 2010) with moderate or high disease activity (DAS28-CRP≥3.2) and ineffectiveness or intolerance of conventional synthetic DMARDs, biological DMARDs and JAK inhibitors. Disease activity in patient with RA was assessed by DAS28-CRP. Our study did not include an examination by a neurologist to detect signs of CS, so the Central Sensitization Inventory (CSI) (part one) was used. The BPI questionnaire was used for assessing clinical pain intensity. The PainDETECT, FSS, FIRST, HAQ questionnaires were used for screening neuropathic pain symptoms (NPS), fatigue, fibromyalgia signs and functional impairment, respectively. The HADS questionnaire was recommended for early diagnosis anxiety and depression disorders.Results. Signs of CS (CSI≥40), with a median of 42 [32; 53], were found in 57.2% of the examined patient. Patients with signs of CS were established to have poorer health measure (PGA – 64.6±13.5 and 53.5±16.8; p=0.001), higher pain intensity in all BPI scales, longer morning stiffness – 90 [30; 180] and 60 [20; 120] minutes (p=0.001), more painful joints – 8 [5; 12] and 7 [4; 10] (p=0.005), worse functional status in HAQ (1.65±0.7 and 1.08±0.5; p=0.001) and higher disease activity in DAS28-CRP (4.9±1.0 and 4.6±0.9; p=0.001) compared to patients without signs of CS. There was also direct correlation between CS and a high frequency of having an NPS (PainDETECT>18) – 34.5% and 10.3% (p=0.001), significant anxiety and depression (HADS>11) – 29,0% and 5.1% (p=0.001) and 26.3% and 4.2% (p=0.001) respectively, fatigue (FSS) – 96.5% and 70.4% (p=0.001), signs of fibromyalgia (FIRST≥5) – 38.4% and 6.1% (p=0.001).Conclusion. The presence of signs of CS in patient with RA significantly enhance many symptoms of disease, being associated with higher pain intensity, fatigue, impaired function, higher incidence of NPS, depression and anxiety, and fibromyalgia.

One of the main tasks of modern complex therapy of rheumatoid arthritis (RA) is to improve the quality of life of patients. To do this, it is necessary not only to achieve remission or low activity, but also to successfully control the main, most painful, manifestations of the disease. Therefore, when evaluating the results of RA treatment, the dynamics of not only standard indices (DAS28 (Disease Activity Score 28), CDAI (Clinical Disease Activity Index), SDAI (Simplified Disease Activity Index)), but also the so-called “patient reported outcomes” (PRO) – a patient’s global assessment of disease activity (PGA), pain, functional disorders and fatigue.This review examines the effect of one of the main classes of anti–rheumatic drugs - biological disease-modifying antirheumatic drugs (bDMARDs) on the PROs. The results of a series of randomized controlled trials are presented, in which changes in PROs were studied using various tumor necrosis factor α (TNF-α) inhibitors, abatacept T-lymphocyte co-stimulation inhibitor, rituximab CD20 inhibitor and interleukin (IL) 6 inhibitors.The use of bDMARDs in combination with methotrexate (MTX) provides a reduction in PGA and pain by 50-60%, functional disorders according to HAQ (Health Assessment Questionnaire) and fatigue according to FACIT-F (Functional Assessment of Chronic Illness Therapy – Fatigue) – by 15-30%. B DMARDs monotherapy (with the exception of the effect of tocilizumab on HAQ) does not exceed MTX monotherapy in its effect on PROs. Monotherapy with tocilizumab provides more favorable dynamics of PGA and pain than monotherapy with TNF-α inhibitors. An important advantage of IL-6 inhibitors is the rapid achievement of a clinical effect, which is noted already in the first 2 weeks after the first administration of the drug.

The goal of treatment of rheumatoid arthritis (RA) is to achieve remission or low disease activity. A wide range of disease-modifying antirheumatic drugs is used for the treatment of RA, including biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). However, even with the use of bDMARDs and JAKi, this goal can be achieved only in 40–60% of patients. Insufficient response to bDMARs and JAKi is the reason for switching to other drugs from the same group, such as tumor necrosis factor-α inhibitors, and to drugs with a different mechanism of action. The need to change therapy may be associated with its ineffectiveness due to various immune, genetic and epigenetic mechanisms, with the development of adverse reactions, as well as with comorbid pathology. To date, there is no certain predictors of effectiveness of a particular bDMARDs and JAKi and of the need and strategy for changing the therapy.The review considers the effectiveness of various classes of bDMARDs and JAKi in RA, the frequency and risk factors associated with the need to switch patients to other drugs, the role of chemokines as promising markers of response to RA treatment.

The prescribing of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (iJAK) during the COVID-19 pandemic requires a balanced approach and tight monitoring of the patients.The aim of the study was to study the effect of bDMARDs and iJAK inhibitors on the condition of patients with rheumatoid arthritis (RA), taking the patients reported outcomes, as well as the incidence of COVID-19 in these patients.Materials and methods. A telephone survey was conducted of 254 patients with RA (average age – 49.8±13.7 years; 64.4% of patients are positive for rheumatoid factor; women – 83.5%; DAS28 score – 5.4±1.6 points), who in the period from January 2020 to June 2021 were prescribed bDMARDs or iJAK for the first time: 148 (58.3%) – rituximab; 57 (22.4%) – tumor necrosis factor α inhibitors; 20 (7.9%) – iJAK; 17 (6.7%) – interleukin 6 inhibitors; 12 (4.7%) – abatacept.Results. At the time of the survey, 204 (80.3%) patients continued taking prescribed medications. The main reason for the interruption of treatment was administrative problems. Synthetic DMARDs (mainly methotrexate and leflunomide) were received by 68.0%, glucocorticoids – 45.3%, nonsteroidal anti-inflammatory drugs – 44.5% of respondents. Among patients treated with bDMARDs or iJAK, 68.1% noted «the state of symptoms acceptable to the patient», the absence of frequent joint pain – 65.3%, the absence of increased fatigue – 14.3%. The incidence of COVID-19 and hospitalization associated with this disease did not differ in individuals who continued and stopped using bDMARDs or iJAK: 41.2% and 44.6%, 13.7% and 14.0%, respectively (p=0.80884). There were no statistically significant differences in the incidence of COVID-19 and hospitalization associated with this disease in patients taking various bDMARDs or iJAK.Conclusion. Despite the COVID-19 pandemic, rituximab remains one of the most popular bDMARDs. About a third of patients receiving bDMARDs or iJAK are not satisfied with their condition. More than 40% of patients who received these drugs suffered COVID-19; 14.0% required hospitalization.

Sexual dimorphism of chronic diseases is a phenomenon determined by differences in the hormonal status of men and women. In this regard, estrogens, which have a complex effect on the body, are of great interest. In particular, estrogens play an important role in the natural control of pain and inflammation. A decrease in estrogen levels associated with menopause or iatrogenic effects (hysterectomy, use of aromotase inhibitors), as well as mutations of genes responsible for the synthesis of structural components of membrane estrogen receptors (ESR1 and ESR2), can significantly reduce the positive effects of these hormones. Deficiency of estrogen can become one of the reasons for the development of serious pathological changes in particular, the formation of chronic pain associated with the pathology of the musculoskeletal system.