The aim of the study – to analyze the effectiveness and tolerability of subcutaneous methotrexate (sc MTX) (Metorthrit; S.C. Rompharm Company S.R.L) in patients with rheumatoid arthritis (RA) with high disease activity and rapid dose escalation, to assess their quality of life (QoL) in real clinical practice.Material and methods. The study included 105 patients, mostly women, with a reliable diagnosis of RA with high disease activity (DAS-28 (Disease Activity Score 28) ≥5.1) aged 18 years and older and ineffectiveness of previous oral MTX therapy for at least 6 months or who had not received MTX. Sc MTX therapy was started at a dose of 15 mg/weekly. During the first month of therapy, a rapid escalation of the sc MTX dose of 2.5 mg/week was performed once a week. until the dose of 22.5 mg/week was reached, then, with insufficient response, the dose of sc MTX could be increased to 25 mg/week. The evaluation of the effectiveness of therapy, functional status, and QoL was carried out after 4–12–18–24 weeks.Results. After a rapid escalation of the sc MTX dose during the first month of the study, at all stages of follow-up, a rapid decrease in disease activity was noted for all standard indices (DAS-28 – from 5.8±0.75 to 2.93±1.05; CDAI (Clinical Disease Activity Score) – from 30.13±8.33 to 7.08±6.07; SDAI (Simplified Disease Activity Score) – from 32.78±9.64 to 7.48±6.53) and the activity index, which was evaluated by the patients themselves (RAPID-3 (Routine Assessment of Patient Index Data 3) from 16.18±4.6 to 5.56±4.66; p≤0.05). The number of patients with high disease activity according to DAS-28 decreased by 2 times by the week 4 of therapy (to 46.2%), after 12 weeks they remained 13.3%, and by week 24 high activity remained only in 4.4% of patients. There was a marked decrease in pain from 65.6±13.07 to 20.5±17.1 mm in VAS (Visual Analogue Score) (p<0.001), which contributed to an improvement in the functional state: the HAQ (Health Assessment Questionnaire) index decreased on average from 1.47±0.65 to 0.64±052 points. Population indicators of functional status (HAQ≤0.5) by the week 24 of therapy were observed in 48.9% of patients. A decrease in the level of fatigue (from 6.25±7.04 to 1.81±1.71 cm according to VAS; p<0.001) was accompanied by a decrease in anxiety (from 7.47±4.03 to 2.36±2.72; p<0.001) and depression (from 7.77±3.84 to 2.50±2.56; p<0.001), as well as improved sleep. By the week 24 of the study, 45% of patients had population-based indicators of QoL according to the EQ-5D index. Glucocorticoids (GC) were completely eliminated in 2/3 of the patients. Patients who did not receive GC had lower disease activity by 24 weeks in all indices: DAS-28 (2.7±0.1 and 3.4±0.2, respectively), CDAI (6.0±0.3 and 10.2±0.1), SDAI (6.4±0.2 and 10.9±0.3) (p<0.05). Patients receiving and not receiving GC had the same number of adverse reactions (p>0.05), however, the number of infections in patients receiving GC was significantly higher (9.5% and 0.0%, respectively; p=0.009). The need for nonsteroidal anti-inflammatory drugs (NSAIDs) at the beginning of the study was in 93.2% of patients on average 21.1 days per month, after 24 weeks, the need for NSAIDs was in 54.4% of patients on average 3.8 days per month. In general, the safety profile of MTX was acceptable.Conclusion. With high RA activity, the tactics of starting therapy with sc MTX at a dose of 15 mg per week and a rapid escalation of its dose of 2.5 mg weekly to 22.5–25 mg/week, allows achieving therapy goals by 3 months in 17.8% of patients, and by 6 months in 54.5%, to quickly improve the QoL, reduce the level of pain, reduce the dose of GC by 3 months of therapy or completely cancel them, reduce the need for NSAIDs by 7 times with an acceptable level of therapy safety.
Under real-world clinical practice together with indices for assessing disease activity and the effectiveness of therapy, drug retention provides critical information on efficacy, safety, compliance and convenience of use.The aim – to obtain data on the safety of netakimab (NTK) in a population of patients with ankylosing spondylitis (AS), including various somatic diseases, as well as to assess retention on therapy during 2 years of observation in real word clinical practice.Materials and methods. Patients were recruited for the study from August 2020 to December 2021 at 23 centers in the Russian Federation. The study included 137 patients who were prescribed netakimab therapy before enrollment. Clinical and medical history data for the first visit were entered retrospectively, and following visits at 12, 24, 52, 76, 104 weeks of therapy were collected within the study. The average age of the patients 42,3 y. O., 34.3% of them with previous biologics therapy.Results. Median observation period was 104 weeks (range 1–137 weeks). At the end of the analyzed period (104 weeks of therapy), 85,5% [95% confidence interval (95% CI): 79.7–91.8] of patients continued treatment with Netakimab. Retention on NTK therapy was slightly better in “bio-naïve” vs patients who received biologics earlier: 88.7% (95% CI: 82.3–95.5) and 78.9% (95% CI: 67.5–92.2), respectively, without significant differences between groups (p=0.16). 21 (15.3%) patients withdrew from study before visit 6. The main end of study reasons was lost to follow-up – 7 (5.1%) patients, and treatment inefficacy – 6 (4.4%) patients. The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein) showed statistically significant decreases from baseline: by three times during the first 3 months of therapy and two times decrease during the first year of treatment. This trend continued in the second year of treatment, although with a lower rate of reduction. By week 104 of therapy, 52.9% (95% CI: 47.3–58.4) reached low disease activity (1.3≤ASDAS<2.1), 21.3% (95% CI: 12.8–29.8) had inactive disease (ASDAS<1.3). Netakimab was well tolerated by patients: AEs, related to therapy according to the investigator’s opinion, were reported in 8 (6.0%) patients.Conclusions. In real-world clinical practice, 85.5% of patients continued treatment with Netakimab at the end of 104 weeks. By 104 weeks 74% patients had low disease activity or inactive disease. Netakimab was well tolerated by most of patients.
The aim – to develop a unified diagnostic algorithm for axial psoriatic arthritis (axPsA).Subjects and methods. 122 patients with psoriatic arthritis (PsA), duration less than 10 years, were included in the study according to CASPAR (The ClASsification for Psoriatic ARthritis) criteria, provided they also had axial involvement. Axial involvement was detected in case of radiographic sacroiliitis ((rSI); bilateral grade ≥2 or unilateral grade ≥3) or SI active according to magnetic resonance imaging (MRI) (MRI-SI), or ≥1 syndesmophyte(s) of the cervical and/or lumbar spine (CS/LS), or facet joints ankyloses of the CS. Patients were evaluated for the presence of inflammatory back pain (IBP) by ASAS (The Assessment of SpondyloArthritis international Society) criteria. Back pain lasting over three months, that did not meet ASAS criteria was considered chronic back pain (chrBP). HLA-B27 antigen status was observed.Results and discussion. IBP was identified in 87 (71.3%), chrBP – in 35 (28.7%) patients, 49 (40.2%) patients had older age (>40 years) at back pain onset. 120 (98.4%) patients had peripheral arthritis, 75 (61.5%) – dactylitis, 69 (56.6%) – enthesitis, 122 (100%) – psoriasis, 90 (73.8%) – nail psoriasis. Isolated axial disease without peripheral arthritis was found in 2 (1.6%) patients. RSI was detected in 85 (69.7%) patients, in 28 of 85 (32.9%) patients rSI developed without IBP. Spinal lesions of the LS and CS were found in 100 (82.0%) patients, chunky “non-marginal” syndesmophytes – in 60 (49.2%), asymmetrical syndesmophytes of the LS – in 22 of 72 (30.6%), paravertebral ossification – in 5 (4.1%) patients. Isolated spinal lesions without rSI were found in 37 (30.3%), isolated spinal lesions without rSI or MRI-SI – in 21 (17.2%) patients. HLA-B27 was observed in 27 of 86 (31.4%) examined patients. Diagnostic algorithm for axPsA was developed. All PsA patients, regardless whether they experienced IBP/chrBP or not, must undergo diagnostic imaging: pelvis, LS and CS X-ray. In patients without rSI, MRI of the sacroiliac joints should be performed. AxPsA diagnosis must be confirmed by imaging. Axial involvement is detected in case of rSI or MRI-SI, or ≥1 syndesmophyte(s) of the CS/LS, or facet joints ankyloses of the CS.
The aim – to compare the efficacy and safety of different doses of colchicine (0.5 mg/day vs 1.0 mg/day) used for the prevention of arthritis attacks in gout patients during the initiation of urate-lowering therapy.Materials and methods. The study included 96 patients diagnosed with gout. Patients were randomized into three groups: those receiving colchicine 0.5 mg/day, colchicine 1 mg/day, and those without anti-inflammatory therapy. All participants were prescribed febuxostat 80 mg/day. The duration of the observation period was 6 months. The frequency and severity of arthritis attacks, as well as the incidence of adverse events, were compared.Results. Patients who did not receive colchicine experienced arthritis attacks more frequently compared to those receiving 0.5 mg/day (p=0.03) and 1 mg/day (p=0.007). In the groups receiving colchicine 0.5 mg/day and 1.0 mg/day, the frequency of attacks did not differ significantly (p=0.6), nor did the proportion of patients who did not experience arthritis attacks – 18 (56%) and 22 (69%), respectively (p=0.3). Among patients not taking colchicine, 9 (28%) did not develop arthritis attacks (p=0.02 compared to those taking 0.5 mg/day and p=0.001 for 1 mg/day). The administration of colchicine 1 mg/day (but not 0,5 mg/day) was associated with lower pain intensity on the visual analog scale during arthritis attacks compared to the non-therapy group (p=0.04). The frequency of adverse events was comparable across the groups.Conclusion. The use of colchicine 0.5 mg/day for the prevention of arthritis attacks in gout patients is justified due to the absence of differences in efficacy compared to the higher dose. However, prescribing colchicine 1 mg/day also demonstrates a good safety profile and may be considered for the prevention of arthritis attacks.
The aim – to evaluate the effectiveness of long-term therapy with Russian rituximab (RTX) biosimilar in Sjögren’s disease (SjD) in real-life clinical practice.Materials and methods. The retrospective study included 53 patients with SjD (Russian 2001 criteria and ACR/ EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) 2016 criteria), observed at the V.A. Nasonova Research Institute of Rheumatology from 2017 to 2024 and receiving long-term RTX therapy (Russian biosimilar Acellbia®, BIOCAD). The signs of clinical and laboratory activity of the disease, stomatological and ophthalmological tests, as well as the incidence of new systemic manifestations and lymphomas were assessed dynamically.Results. The median duration of RTX therapy was 27 [19; 55] months, and the median total dose was 4 [3.5; 5.5] g. Before the therapy, 13 (25%) patients had recurrent parotitis, which was relieved in all patients during the therapy. Persistent enlargement of the salivary glands was observed in 10 (20.4%) patients, in 9 of them it was relieved. A significant increase in stimulated saliva flow was found (from 1.5 [0.5; 3] to 2.4 [1.4; 3.5] ml; p=0.002), an increase in salivation was found in 51% of patients, stabilization in 28.6%, and deterioration in 20.4%. When assessing the ultrasound dynamics of the salivary glands, the size of hypoechoic avascular lesions significantly decreased (from 1.8 [1.3; 2.3] to 1.3 [1.1; 1.5] mm; p<0.001), and according to the ultrasound activity index, stabilization was noted in 67.4% of patients, improvement in 27.9%, and deterioration in 4.7% of patients. When assessing the dynamics of sialography, the size of cavities significantly decreased (from 1.5 [1.5; 2.5] to 1.0 [0; 1.5] mm; p<0.001), and according to the assessment of sialographic stages, stabilization was noted in 67.5% of patients, improvement in 32.5% of patients, and deterioration was not noted in any patient. When assessing the lacrimal glands function, a significant increase in lacrimation was found according to the stimulated Schirmer’s test (from 6 [3.75; 12] to 8 [5; 15] mm; p=0.005); an increase in lacrimation was noted in 38% of patients, stabilization in 40.6%, and a decrease in 21.4%. When assessing the tear break-up time, a tendency towards its increase was noted, but statistically insignificant (from 5 [3.75; 9.25] to 5.5 [4; 9] sec; p=0.35). Corneal epitheliopathy during the therapy was relieved in 44% and persisted in 56% of patients; worsening of corneal epitheliopathy during the treatment was observed in a few patients, while no cases of ulcer formation or perforation of the cornea were recorded. During the therapy, a significant decrease in the levels of erythrocyte sedimentation rate, gamma globulins, IgG, IgA, IgM, rheumatoid factor, an increase in the C3 complement level, and the elimination of monoclonal gammopathy were observed, while the dynamics of the C4 complement level and cryoglobulinemia were multidirectional. The median duration of B lymphocyte depletion was 5 [4; 6] months, constant depletion could be maintained only in 59.6% of patients. During the therapy, the SjD systemic activity index (ESSDAI, EULAR Sjögren’s Syndrome Disease Activity Index) significantly decreased (from 5 [2; 8] to 1 [0; 3] points; p<0.001), and minimal clinically important improvement of this index was achieved in 66.6% of patients. During the observation, one patient developed a new skin lesion (lupus chilblain); no other new systemic manifestations or lymphomas were registered.Conclusion. According to our retrospective study conducted in real-life clinical practice, long-term therapy with Russian RTX biosimilar in most cases (60–80%) led to stabilization or improvement of SjD manifestations. RTX can be used to treat not only systemic but also glandular manifestations of the disease. Given the lack of an optimal response to RTX therapy in a number of SjD patients, it is necessary to study the effectiveness of drugs that lead to a deeper depletion of B lymphocytes.
