One of the most promising approaches to depletion-restitution therapy is the development and use of drugs based on bispecific monoclonal antibodies (bsAbs). Therapeutic bsAbs are genetically engineered biological products (biologics) based on immunoglobulin molecules capable of simultaneously binding multiple antigens, making them a promising platform for novel drugs. A specific type of such agent, which incorporates at least two antigen-binding (Fab) fragments within a single immunoglobulin molecule – one targeting a specific cell-surface receptor and the other binding and activating to the CD3ε domain of CD3 molecule of the T-cell receptor complex – has been termed a bispecific T-cell engager (BiTE).
Currently, BiTE molecules that engage effector cells of the humoral immune system are the most clinically advanced subclass of bsAbs. Their ability to deplete target cells in peripheral blood and tissues has been clearly demonstrated in the treatment of resistant hematological malignancies such as B-cell precursor acute lymphoblastic leukemia, various lymphoproliferative disorders, and plasma cell dyscrasias. Recent years have seen attempts to repurpose bsAbs for the treatment of refractory, prognostically unfavorable forms of systemic autoimmune rheumatic diseases (SARDs), supported by theoretical rationale, experimental evidence, and parallels with successful CAR-T cell therapy.
Beyond BiTEs, the bsAb platform also enables development of biologics with extended pharmacokinetics, multi-cytokine targeting potential for synergistic suppression of inflammation, and checkpoint-directed modulation of targeted cell functional activity.
Advantages such as standardized manufacturing, off-the-shelf availability, predictable pharmacokinetics (with a known and limited half-life), flexible dosing regimens enabling slow escalation of the dose, the possibility of individualizing treatment duration and dosing frequency, the feasibility of repeated treatment cycles, the option to discontinue therapy in case of adverse events, and the significantly lower cost of short low-dose treatment cycles compared to CAR-T cell therapy – all these make bsAb-based strategies a highly attractive priority for next-generation depletion-restitution therapies for SARDs.

Genetic vasculopathies can mimic large and medium vessel vasculitis, while occlusive non-vasculitic vasculopathies and infections are often mimickers of small and medium vessel vasculitis. Most of these conditions are as severe as systemic vasculitides but require fundamentally different, and often urgent treatment approaches.

This article presents the current guidelines of the American College of Rheumatology (ACR) on the screening, treatment, and management of patients with lupus nephritis (LN), accompanied by comments from Russian experts. The discussion includes indications for renal biopsy, a new approach to the treatment of various classes of LN using triple and dual immunosuppressive therapy, as well as recommended glucocorticoid dosages and treatment durations.

The potential link between targeted therapies and malignancies (MN) in patients with inflammatory joint diseases and a history of MNs remains a frequent concern in routine rheumatological practice.
In 2024, the EULAR (European Alliance of Associations for Rheumatology) task force formulated five overarching principles and seven hypotheses regarding the initiation of targeted therapy in patients with active arthritis and MN in remission, as well as one hypothesis for patients with active arthritis who have not achieved remission of the oncological disease.
Key considerations included: a) the necessity of assessing the individual risk of cancer recurrence based on patient-specific factors, the type of MN, and the underlying disease; b) the importance of close cooperation with oncology specialists and determining the therapeutic strategy through shared decision-making between the patient and rheumatologist; c) the need for the timely initiation of appropriate targeted arthritis therapy in patients with cancer remission; d) a recommendation to use Janus kinase inhibitors and abatacept cautiously and only when no alternatives are available, due to the lack of data on their use in patients with prior MN.
These guidelines identify specific points that require particular attention when prescribing targeted therapy to patients with active arthritis and a history of MN.

Objective: to investigate possible associations between genetic, clinical, laboratory, and demographic parameters and the level of pain in the early postoperative (p/o) period, the need for opioid analgesics, and gastrointestinal symptoms in patients who underwent primary total knee (TKR) or hip replacement (THR).
Material and methods. Sixty-one patients hospitalized for THR or TKR were included in the study. P/o pain relief was achieved using nonsteroidal anti-inflammatory drugs (NSAIDs) – ketoprofen or ketorolac – with tramadol prescribed "on demand." Pain was assessed in all patients using the numeric rating scale (NRS) on postoperative days 1–5. The amount of opioid analgesics used during hospitalization was recorded. Gene polymorphisms of CYP2C9, CYP2C8, PTGS1, PTGS2, ABCB1, CYP2D6, OPRM1, COMT, and C3orf20 were analyzed using real-time polymerase chain reaction.
Results and discussion. Patients with the AC genotype of CYP2C9*3 experienced less intense pain on postoperative day 1 (4.5±1.0 vs. 7.0±2.3; p=0.03) and required fewer opioids during hospitalization (20.0±11.5 vs. 28.0±7.4 morphine equivalent units; p=0.04) compared to those with the AA genotype. Carriers of the CC genotype of the rs1045642 polymorphism of the ABCB1 gene reported less pain on day 5 (1.5±0.7 vs. 3.7±1.2; p=0.04) than those with the CT genotype. Patients with the AA genotype of rs1799971 in the OPRM1 gene required more opioids in p/o period than those with AG + GG genotypes (28.4±7.1 vs. 21.6±9.8 morphine equivalent units; p=0.03). Patients with the GG genotype of rs12496846 in the C3orf20 gene experienced more intense pain on p/o day 4 (6.0±1.41) than those with the AA genotype (2.60±1.50; p=0.002).
Conclusion. Following THR and TKR, pain intensity and/or opioid use were associated with patients’ pharmacogenetic profiles in CYP2C9, ABCB1, OPRM1, and C3orf20.

Objective: to assess the trends in overall incidence and the distribution of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (AAV) in the adult population in federal district and across the Russian Federation during 2022–2023, based on data from the Nasonova Research Institute of Rheumatology.
Material and methods. The study is based on data collected via a federal-level inquiry addressed to regional healthcare departments concerning the organization of care and drug provision for patients with AAV in 2022–2023. The responses were qualitatively and quantitatively analyzed by experts from the N.A. Semashko National Research Institute of Public Health (Semashko NRIPH). Additionally, a retrospective single-center study was conducted involving adult patients (≥18 years) with AAV who received outpatient or inpatient care at the V.A. Nasonova Research Institute of Rheumatology (Nasonova RIR) from September 1, 2020, to October 1, 2024, with data obtained from the “Interin” system. Incidence was analyzed in absolute (the total number of registered patients aged ≥18) numbers and relative numbers (per 100,000 adult population) across Russia, in eight federal districts, and three climate/geography-based regions (Northern, Central, Southern). The frequency of antemortem kidney and/or nasal mucosa biopsy for diagnosis of AAV was also assessed.
Results and discussion. According to Semashko NRIPH, a total of 1,785 AAV patients were identified during 2022–2023. The national incidence of granulomatosis with polyangiitis (GPA) ranged from 2.63 to 1.86 per 100,000, microscopic polyangiitis (MPA) from 0.79 to 1.11, and eosinophilic granulomatosis with polyangiitis (EGPA) from 1.16 to 0.98. The greatest incidence and maximal rate of decrease was seen in GPA (-29.28%) and EGPA (-15.52%), while MPA showed a maximal increase in incidence (+40.51%) in the Northern region. Substantial differences were noted across federal districts.
Based on data from the Nasonova RIR, AAV was confirmed in 506 patients, most of whom were women (63%) from the Central region (p<0.001), with a gender gradient by region. Among 67 (13.2%) ANCA-negative patients with atypical presentations, kidney biopsy was more commonly performed (71.6%) than nasal mucosa biopsy (28.3%), p<0.001.
Conclusion. This pilot study revealed regional and gender-related differences in AAV incidence across Russia, as well as low frequency of antemortem biopsy of kidney/nasal mucosa. These findings warrant further in-depth investigation into factors influencing these trends.

Objective: To investigate key risk factors associated with knee pain in early-stage osteoarthritis (OA).
Material and methods. The study included 109 women aged 35–75 years with knee pain lasting no more than one year and minimal radiographic changes (Kellgren–Lawrence grades 0–II). For each patient we filled in a personalized case form including anthropometric data, medical history, physical examination findings, pain and health status assessments using visual analog scale (VAS), and questionnaires (WOMAC, KOOS, DN4), along with information on comorbidities. All participants underwent standard knee radiography, ultrasound examination, and laboratory testing.
Results and discussion. One in six patients (15%) reported moderate or severe knee pain (≥40 mm on VAS). Patients with more intense pain were older than those with VAS <40 mm (median age 52.5 [42; 62.5] vs. 44 [38; 52] years; p=0.02) and had a higher body mass index (28 [25; 31.6] vs. 24 [21; 28] kg/m2; p=0.04). Statistically significant differences were also observed in OA severity: the high-pain group had higher WOMAC and all its components’ scores (median 1245 [872; 1510] vs. 248 [90; 410] mm; p<0.001), lower self-rated health status (60 [47; 80] vs. 29.5 [10; 50] mm; p<0.001), lower KOOS total scores and its components’ scores (44 [37; 67] vs. 79 [63; 88] %; p<0.001), and more frequent detection of synovitis on examination (50% vs. 19.3%; p<0.001) and in the past history (75% vs. 31.1%; p=0.008). Flexion restriction (50% vs. 19.3%; p=0.01), presence of osteophytes on ultrasound (50% vs. 10.75%; p<0.001), metabolic syndrome (56.25% vs. 25.8%; p=0.03), and postmenopausal status (68.75% vs. 35.48%; p=0.01) were also more frequent.
A discriminant model was developed to predict the risk of pain ≥40 mm on VAS, incorporating WOMAC functional limitations, presence of metabolic syndrome, ultrasound-detected osteophytes, and clinically significant synovitis. The model achieved an accuracy of 90.8%. Predictive performance was confirmed by ROC analysis (AUC=0.898, 95% CI 0.794–1.002), indicating high prognostic accuracy.
Conclusion. Severe knee pain at early stages of OA is associated with functional impairment according to WOMAC, clinical synovitis, ultrasounddetected osteophytes, and metabolic syndrome. These risk factors and the developed predictive model may be useful for planning individualized preventive and therapeutic strategies in OA patients.

Objective: To analyze clinical and imaging characteristics of patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) with spinal involvement (axial PsA, axPsA) and to develop principles for the differential diagnosis between axPsA and axSpA.
Material and methods. A total of 222 patients were examined: 108 with axSpA (Group 1) and 114 with axPsA (Group 2). Group 1 included patients meeting the criteria for axSpA/ankylosing spondylitis (AS); Group 2 included patients meeting the CASPAR criteria for PsA with axial involvement. Axial involvement was defined as radiographically confirmed (rc) sacroiliitis (SI; bilateral SI ≥ grade II or unilateral SI ≥ grade III), active SI on MRI, or ≥1 syndesmophyte in the cervical (CS) and/or lumbar (LS) spine. Inflammatory back pain (IBP) was assessed using ASAS criteria.
Results and discussion. Patients in Group 1 were younger (p<0.001), more frequently HLA-B27 positive (p<0.001), and more often had IBP (p=0.001). In Group 2, later onset of back pain (>40 years) was more common (p<0.001), along with peripheral arthritis (p<0.001), dactylitis (p=0.004), and skin psoriasis (p<0.001). Nail psoriasis was observed exclusively in Group 2 (p<0.001). Heel enthesitis was more frequent in Group 1 (p<0.001). Patients in Group 2 had higher BASDAI scores (p<0.001) and more often had high ASDAS-CRP disease activity (p<0.001). They also had higher BASFI scores (p=0.008), pain scores (p=0.002), and patient global assessment (p=0.021).
rcSI and sacroiliac joint ankylosis were more common in Group 1 (p=0.03 and p=0.006, respectevly). Group 2 more frequently exhibited syndesmophytes in the LS (p<0.001) and CS (p=0.004), as well as bulky (p<0.001), asymmetric (p=0.006), and non-bridging (p<0.001) syndesmophytes. Vertebral changes in the absence of SI (p<0.001), higher mSASSS scores (p<0.001), and more frequent erosions of hand and foot joints, multiple erosions, osteolysis, juxta-articular new bone formation (p<0.001 for all), and joint ankylosis (p=0.008) were also observed in Group 2, along with elevated CRP levels (p=0.002).
Conclusion: This study revealed several genetic, demographic, clinical, and imaging differences that collectively enable the differential diagnosis between axSpA/AS and axPsA.

Objective: to assess the efficacy and safety of olokizumab (OKZ) in routine clinical practice in patients with rheumatoid arthritis (RA) in Kazakhstan.
Material and methods. A 24-week, single-center observational study included 26 RA patients with moderate to high disease activity according to DAS28. All patients received OKZ 64 mg subcutaneously every 4 weeks in combination with methotrexate. Disease activity according to DAS28- CRP was assessed at baseline and at weeks 4, 12, and 24.
Results and discussion. Women comprised 88% of the study population. All patients were seropositive for rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies. The median age was 53 [24; 73] years, and the mean baseline DAS28-CRP score was 5.5±1.3. By week 24, a good or moderate response according to EULAR criteria was observed in 19 (73.0%) patients. DAS28-CRP remission was achieved in 50.0% of cases. OKZ was generally well tolerated, with no unexpected adverse events reported.
Conclusion. This real-world study confirmed the efficacy and safety of OKZ in a predominantly Asian population of RA patients. The results are consistent with those of previous randomized controlled trials, supporting the use of OKZ in routine clinical practice as an effective and well-tolerated treatment option for RA.

In managing elderly patients with rheumatoid arthritis (RA), it is essential to maintain a balance between treatment efficacy and safety, particularly concerning the use of glucocorticoids (GCs). Despite decades of GC use in comprehensive RA therapy, questions regarding the optimal safe dose, treatment duration, and the necessity of discontinuation or complete avoidance of these drugs remain unresolved.
Objective: to assess the efficacy and safety of long-term low-dose GC use in elderly RA patients based on real-world clinical data.
Material and methods. A retrospective cross-sectional analysis was conducted on 967 patients with active RA (ACR/EULAR, 2010) hospitalized in a specialized rheumatology center, who were non-responders to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and required initiation/resumption/switch of biologic DMARDs (bDMARDs) or targeted synthetic DMARDs. From the total sample, patients who had been receiving oral GCs for ≥6 months were selected (n=658). Group A (n=385) included young and middle-aged patients (18–59 years), and Group B (n=225) included elderly patients (≥60 years). Clinical and laboratory disease activity, extra-articular manifestations, severity and progression of RA, and pharmacotherapy features were assessed in all patients. Comorbidities were evaluated in all patients using the Cumulative Illness Rating Scale (CIRS).
Results and discussion. The median duration of continuous GC use in elderly RA patients was 43 [13.5; 125] months, with a mean daily dose of 6.2±3.3 mg. The duration of GC therapy positively correlated with the time from arthritis onset to initiation of bDMARDs. Despite comparable inflammatory activity indicators (DAS28, SDAI, CDAI, etc.), RA in elderly patients was characterized by significantly longer disease duration (p<0.0001), greater severity, higher frequency of rheumatoid factor positivity and extra-articular manifestations of RA (p=0.0006), more frequent joint surgeries (p<0.0001), including total joint replacement (p=0.0009) and small joint arthroplasty (p=0.003). Compared to younger patients, elderly RA patients had significantly higher rates of comorbid conditions: coronary artery disease (p<0.0001), myocardial infarction (p=0.03), cerebrovascular disease (p=0.0003), polyneuropathy (p=0.004), chronic gastritis (p=0.002), interstitial lung disease (p<0.0001), chronic kidney disease (p<0.0001), type 2 diabetes mellitus (p=0.006), cataracts (p<0.0001), obesity (p<0.0001), and osteoporosis (p<0.0001), which resulted in a significantly higher CIRS multimorbidity index (p<0.0001).
Conclusion. Long-term use of low-dose GCs in elderly RA patients was not associated with improved disease control in terms of disease activity or radiographic progression, nor with rational use of csDMARDs. It significantly delayed the timely initiation of bDMARDs and contributed to increased multimorbidity burden overall.

Leading Russian and international experts recognize the necessity of incorporating patient-reported outcomes (PROs) into the dynamic monitoring of rheumatoid arthritis (RA) patients. An integral indicator of general well-being and treatment satisfaction is the Patient Acceptable Symptom State (PASS).
Objective: To assess patient satisfaction with their health status and treatment outcomes in RA and to evaluate its relationship with key disease manifestations through remote PROs assessment.
Material and methods. From January 2023 to November 2024, an online survey was conducted involving 2,115 RA patients (88.3% women, mean age 46.4±13.9 years, median disease duration 6 [3; 13] years). The survey assessed demographics, therapy, PASS, and PROs (pain, fatigue, anxiety, depression, daily activity limitations, patient global assessment [PGA], using a numerical rating scale [NRS], 0–10). Among respondents, 80% were receiving conventional synthetic disease-modifing antirheumatic drugs (DMARDs), 23.8% biologic DMARDs (bDMARDs) or Janus kinase inhibitors (JAKi). Glucocorticoids (GCs) were used by 39.7%, and nonsteroidal anti-inflammatory drugs (NSAIDs ) by 67.9% of patients.
Results and discussion. A positive assessment of their health status (PASS+) was reported by 45.8% of patients. Mean NRS scores were: pain – 5.6±2.7, fatigue – 6.2±2.7, PGA – 5.5±2.5, median anxiety – 5 [3; 8], depression – 5 [2; 7], daily activity limitations – 5 [3; 7]. Dissatisfaction (PASS-) was associated with male gender, moderate (≥4) or high (≥7) NRS PRO scores, and the use of GCs and NSAIDs. bDMARD and JAKi therapy showed an inverse association with PASS-. A binary logistic regression model was developed to predict PASS- in RA patients with an accuracy of up to 71%. ROC curve analysis revealed a threshold value of the logistic function P at 49.6%, area under the curve (AUC) – 0.740 (95% CI 0.718–0.762), model sensitivity – 82%, specificity – 60%.
Conclusion. Fewer than half of RA patients were satisfied with their health status when assessed remotely. PASS is closely associated with PROs and may serve as an integral indicator of health status and treatment satisfaction in RA.

Objective: to assess the effect of a combination of glucosamine hydrochloride (GH) 500 mg and chondroitin sulfate (CS) 500 mg (Artra®) on systemic inflammation markers in patients with knee osteoarthritis (KOA).
Material and methods. The study included 70 patients with a confirmed diagnosis of KOA stage II–III and walking pain ≥4 points on a numerical rating scale (NRS). Study duration was 3 months. All patients received Artra® and, if necessary, topical nonsteroidal anti-inflammatory drugs (NSAIDs). Treatment efficacy was evaluated by changes in pain according to NRS, the WOMAC index, and patient global assessment of health status (PGA) using a visual analogue scale (VAS). C-reactive protein (CRP) levels were measured during visits 1 and 3 in all patients; 40 patients also had their serum levels of 17 cytokines, chemokines, and growth factors assessed.
Results and discussion. After 3 months of treatment, there was a rapid and significant decrease in pain according to NRS (from 5 [5; 6] to 3 [2; 4] points), pain on WOMAC (from 9 [7; 11] to 5 [3; 8] points), stiffness on WOMAC (from 4 [3; 5] to 3 [1; 4] points), improvement in physical function on WOMAC (from 36 [24; 41] to 23.5 [12; 32] points), and PGA (from 50 [50; 70] to 65 [58; 75] mm), p<0.0001 for all comparisons. A decrease was also observed in the number of patients with clinically apparent synovitis (p=0.04) and limited range of motion in the knee joint (p<0.0001). A significant advantage of the GH and CS combination is its impact on inflammatory markers – in particular, a reduction in tumor necrosis factor alpha (TNFα) levels (p=0.04).
Conclusion. In patients with KOA, Artra® demonstrated a rapid symptomatic effect, which continued to increase over the 3-month observation period. Our study confirmed the more subtle molecular mechanisms behind the beneficial effects of the GH and CS combination through suppression of inflammatory mediator production, particularly TNFα. These findings suggest a systemic effect of the drug, making it particularly promising for treating patients with comorbidities.

The pathogenesis and diagnostic approaches to scleroderma renal crisis (SRC) – an acute “scleroderma kidney” – a severe and life-threatening complication of systemic sclerosis (SSc) characterized by high mortality, are discussed. Due to limited understanding of the underlying pathogenic mechanisms, a standardized treatment for SRC has not been developed.
We describe the development of acute SRC in a 43-year-old female patient with diffuse form of SSc of 1.5 years’ duration, rapidly progressive disease course, and internal organ involvement associated with high immunological activity. This case is notable in that the renal crisis developed during hospitalization and was observed from the earliest days under well-documented therapy. The treatment involved the use of several agents with different mechanisms of action, including rituximab, mycophenolate mofetil, a phosphodiesterase-5 inhibitor (sildenafil), and courses of prostanoids. The glucocorticoid dose remained low (methylprednisolone 8 mg/day). Complete resolution of SRC was achieved with restoration of renal function.

According to current understanding of the mechanisms underlying primary immunodeficiencies (PIDs) and their clinical course, there is a clear and clinically significant association between this group of disorders and autoimmune manifestations (AIMs).
This article presents up-to-date information on AIMs in patients with PIDs, with a focus on the most common conditions and key clinical features that warrant consideration of PIDs in the differential diagnosis of patients with rheumatic diseases.

Systemic lupus erythematosus is a complex autoimmune disease in which more than one-third of patients develop lupus nephritis (LN), leading to chronic kidney disease and end-stage renal failure. The treatment of LN has always been a challenge. Tacrolimus is an effective immunosuppressant that has been increasingly used in recent years for the treatment of LN.

Controlling acute and chronic musculoskeletal pain (MSP) is a priority in the management of patients with musculoskeletal disorders. This includes widespread conditions such as non-specific back pain (NSBP), osteoarthritis (OA), and periarticular soft tissue disorders, affecting over 1 billion people worldwide. Modern therapy often fails to achieve satisfactory results in managing MSP: according to several studies, more than 50% of patients are dissatisfied with symptom control. This is due to the complex, multifactorial pathogenesis of MSP, involving persistent inflammation, inadequate tissue repair, nociceptive system dysfunction, biomechanical disturbances, and psycho-emotional factors.
Therefore, the mainstay of pain management today is a multimodal approach that utilizes treatments and agents with different mechanisms of action to achieve a synergistic analgesic effect. One widely used strategy to enhance analgesic efficacy is the combination of analgesics with B-group vitamins (B1 – thiamine, B6 – pyridoxine, B12 – cyanocobalamin). B-vitamins exert a wide range of beneficial effects: they normalize neuronal energy metabolism, suppress peripheral and central sensitization, and possess anti-inflammatory, anabolic, and antioxidant properties. The combination of non-steroidal anti-inflammatory drugs with B-vitamins is commonly used in cases of acute NSBP and is included in current Russian treatment guidelines for this condition. The shared pathogenesis of MSP supports the rationale for the use of B-vitamins in managing pain associated with other musculoskeletal disorders, particularly OA.

This publication presents expert recommendations based on an objective analysis of results from evidence-based studies, systematic reviews, and meta-analyses, as well as on the authors' own clinical experience in using a new category of collagen-containing agents for the prevention and treatment of osteoarthritis.