Использование метотрексата в лечении псориаза и псориатического артрита

Objective: To analyze the results of using methotrexate (MT) in the treatment of psoriasis and psoriatic arthritis (PsA). Results. The mechanism of action of MT, the historical aspects of its use in the treatment of psoriasis and PsA, and the data of clinical trials of the efficacy and safety of the drug are considered. MT therapy is shown to cause a high rate of adverse reactions, which requires measures to prevent and treat adverse events. MT has been found to be frequently used in different combinations, including with other disease-modifying antirheumatic drugs (sulfasalazine), prednisolone, and biological agents, such as tumor necrosis factor inhibitors. In accordance with the European S3-guidelines S3 on the systemic treatment of psoriasis, MT (15-22.5 mg weekly) should be recommended from the results of randomized clinical trials and the extensive clinical experience with this drug. In terms of the present-day views, the indications for immunosuppressive therapy for PsA may be expanded it should be initiated in the early stage of the disease, particularly in its severe forms, until there are destructive changes in the osteoarticular apparatus. Conclusion. MT is an effective drug to treat psoriasis and PsA. It is recommended for use in moderate and severe peripheral arthritis (Grade B) and skin lesions (Grade A).Цель исследования — анализ результатов применения метотрексата (МТ) в лечении псориаза и псориатического артрита (ПсА). Результаты исследования. Рассмотрены механизм действия МТ, исторические аспекты применения препарата в лечении псориаза и ПсА, данные клинических исследований эффективности и безопасности препарата. Показана высокая частота побочных реакций при проведении терапии МТ, что требует выполнения мероприятий, направленных на профилактику и лечение нежелательных явлений. Установлено, что МТ часто используется в разных комбинациях, в том числе с другими базисными противовоспалительными препаратами (сульфасалазин), преднизолоном и биологическими препаратами, такими как ингибиторы фактора некроза опухоли. В соответствии с Европейскими рекомендациями S3 по системному лечению псориаза МТ (15—22,5 мг в неделю) следует рекомендовать исходя из результатов рандомизированных клинических исследований и обширного клинического опыта применения этого препарата. С учетом современных представлений показания к иммуносупрессивной терапии при ПсА могут быть расширены — ее следует начинать в ранней стадии заболевания, особенно при тяжелых формах, до появления деструктивных изменений в костно-суставном аппарате. Заключение. МТ является эффективным лекарственным средством для лечения псориаза и ПсА. Он рекомендован к применению при периферическом артрите средней и тяжелой степени (степень доказательности В) и поражениях кожи (степень доказательности А)

THE EFFECT OF AN ANTI-TUMOR NECROSIS FACTOR-? AGENT ON DISEASE ACTIVITY,BLOOD RHEOLOGICAL PROPERTIES, AND THE ARTERIAL WALL IN PSORIATIC ARTHRITIS

Vascular dysfunction and inflammation in psoriatic arthritis (PsA) share the same pathogenetic mechanism wherein the proinflammatory cytokine tumor necrosis factor- (TNF-) plays a key role. Treatment with anti-TNF- agents is effective in inhibiting inflammation in PsA; however, their effect on the wall of large arteries has not been studied. Objective. To evaluate the effect of Adalimumab (ADA) on the arterial wall and blood rheological properties in PsA. Subjects and methods. Eighteen patients with PsA [12 women and 6 men; mean age 43.1±10.2 years; disease activity scores (DAS), 4.78 (4.0; 5.45)] were subcutaneously injected ADA, 40 mg/every two weeks, for 12 weeks. The investigators assessed the vascular wall, by measuring the mean and maximum common carotid intima-media thickness (IMT) by ultrasound duplex scanning, and arterial rigidity (AR), by determining the refraction index (RI,%) and the rigidity index by digital volume photoplethysmography and Doppler study measuring the aortic pulse wave velocity (PWV) in the carotid-femoral segment (Micromedical, UK), before and after treatment. Erythrocyte aggregation (EA) parameters [Т1 (sec), Kt (c.u.); (sec-1), I2,5 (%)] were measured recording the rate of inverse light scattering and the levels of blood lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)], and atherogenicity coefficient (AC) by routine methods on an automated Express plus analyzer (Bayer, Germany) at baseline, 4, and 12 weeks. The median and the interquartile range [Me (Q25; Q75)] were calculated; the changes in the parameters were estimated by the Wilcoxon test (Wt) and the Friedman test (Ft) for dependent samples;

Cytokine profile in psoriatic arthritis: search for relationships with inflammation and blood rheological properties

Objective. To estimate the serum levels of interleukins (IL) 6 and 10, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in patients with psoriatic arthritis (PSA) and their relationship with the clinical and laboratory parameters of inflammation and with erythrocyte aggregation (EA). Material and methods. The authors measured the serum levels of C-reactive protein (CRP) by immunonephelometry (BN, ProSPEC, Siemens) and those of TNF-α, IL-6 and IL-10, and VEGF by X-MAP technology using a BioPlex-200 system (Panel Human 27-Plex Bio-Rad, USA) in 80 patients with PSA [45 women and 35 men; mean age 41.7±10.5 years, mean duration of PSA and psoriasis was 5.0 (2.0; 12,5) and 15 (4; 26) years, respectively; DAS 3.9 (3.09; 5.16)]. The blood samples from 16 healthy donors matched to the examinees for gender and age served as a control. The parameters of EA [Т1(с); Кt (arb. units); β (с-1), I2,5 (%)] were estimated, by recording the rate of back light scattering. The median (Me) and interquartile range [Q25; Q75], and mean and standard deviations (M±σ) were calculated; the indicators were compared by the Mann-Whitney test and Student's t test. Correlation analysis was made using the Spearman rank correlation coefficient (R); p < 0.05 was considered statistically significant. Results. There were significantly higher serum levels of IL-6 and IL-10, TNF-α, and VEGF in patients with PSA than in the controls, and impaired blood rheological properties. There were significant correlations of the level of most cytokines (IL-6 and IL-10, VEGF) with both the values of the clinical and laboratory activity of PSA (self-rated pain, the number of swollen and tender joints, a physician's assessment of disease activity, DAS, erythrocyte sedimentation rate, and fibrinogen) and most parameters of EA (Т1, Kt и I2.5). No significant relationships were found between VEGF and CRP. Conclusion. The enhanced clinical and laboratory activity of PSA is attended by the systemic activation of immunological mediators of inflammation and neoangiogenesis and by impaired blood rheological properties, which supports the interaction of these factors in the immunopathogenesis of the diseases

Long-term effectiveness and persistence of ustekinumab and TNF inhibitors in patients with psoriatic arthritis: final 3-year results from the PsABio real-world study

Objectives: To evaluate real-world persistence and effectiveness of the IL-12/23 inhibitor, ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis over 3 years. Methods: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or a TNFi. Persistence and effectiveness (achievement of clinical Disease Activity for PSA (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very LDA (MDA/VLDA)) were assessed every 6 months. Safety data were collected over 3 years. Analyses to compare the modes of action were adjusted on baseline differences by propensity scores (PS). Results: In 895 patients (mean age 49.8 years, 44.7% males), at 3 years, the proportion of patients still on their initial treatments was similar with ustekinumab (49.9%) and TNFi (47.8%). No difference was seen in the risk of stopping/switching; PS-adjusted hazard ratio (95% CI) for stopping/switching ustekinumab versus TNFi was 0.87 (0.68 to 1.11). In the overall population, cDAPSA LDA/remission was achieved in 58.6%/31.4% ustekinumab-treated and 69.8%/45.0% TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63 to 1.26) for cDAPSA LDA; 0.72 (0.50 to 1.05) for remission. MDA/VLDA was achieved in 41.4%/19.2% of ustekinumab-treated and 54.2%/26.9% of TNFi-treated patients with overlapping PS-adjusted ORs. A greater percentage of TNFi-treated patients achieved effectiveness outcomes. Both treatments exhibited good long-term safety profiles, although ustekinumab-treated patients had a lower rate of adverse events (AEs) versus TNFi. Conclusion: At 3 years, there was generally comparable persistence after ustekinumab or TNFi treatment, but AE rates were lower with ustekinumab

Management of Peripheral Arthritis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations

Use of methotrexate in the treatment of psoriasis and psoriatic arthritis

Objective: To analyze the results of using methotrexate (MT) in the treatment of psoriasis and psoriatic arthritis (PsA). Results. The mechanism of action of MT, the historical aspects of its use in the treatment of psoriasis and PsA, and the data of clinical trials of the efficacy and safety of the drug are considered. MT therapy is shown to cause a high rate of adverse reactions, which requires measures to prevent and treat adverse events. MT has been found to be frequently used in different combinations, including with other disease-modifying antirheumatic drugs (sulfasalazine), prednisolone, and biological agents, such as tumor necrosis factor inhibitors. In accordance with the European S3-guidelines S3 on the systemic treatment of psoriasis, MT (15-22.5 mg weekly) should be recommended from the results of randomized clinical trials and the extensive clinical experience with this drug. In terms of the present-day views, the indications for immunosuppressive therapy for PsA may be expanded it should be initiated in the early stage of the disease, particularly in its severe forms, until there are destructive changes in the osteoarticular apparatus. Conclusion. MT is an effective drug to treat psoriasis and PsA. It is recommended for use in moderate and severe peripheral arthritis (Grade B) and skin lesions (Grade A)

THE DIAGNOSTIC VALUE OF CLINICAL EXAMINATION AND ULTRASOUND STUDY OF ENTHESES FOR EARLY DETECTION OF PSORIATIC AND RHEUMATOID ARTHRITIS: REMARC STUDY

The diagnosis of enthesitis can help in differentiating early psoriatic arthritis (ePsA) from early rheumatoid arthritis (eRA).Objective. To estimate the diagnostic value of detecting enthesitis during clinical examination and ultrasound in ePsA and eRA.Subjects and methods. The trial included 36 patients with ePsA and 33 with eRA. Entheses were evaluated using the Leeds Enthesitis Index (LEI): lateral humeral epicondyle and medial femoral condyle (MFC), Achilles tendon insertion site (ATAP), and plantar fascia (PF) point on the right and on the left. Enthesitis (on ultrasound) presented with thickening, reduced echo density, and vascularization at Doppler energy imaging. DAS, DAS28, SDAI, CDAI, M±SD, Me [25th, 75th percentile], t-test, Fisher's exact test, χ2test, U test, and Spearman correlation coefficients (R) were calculated; the value p &lt; 0.05 was considered statistically significant.Results. Clinical examination revealed enthesitis in 41.6% of the patients with ePsA and in 39.4% of those with eRA (p &gt;0.05). No significant differences were found between ePsA and eRA according to LEI (0.5 [0; 2] and 1 [0; 2] and to LEI+PF (1 [0; 2] and 1 [0; 2], respectively). Enthesitis of MFC and PF was significantly more frequently detected in ePsA than in eRA – 12 (33.3%)/2 (6.1%) and 10 (27.8%)/2 (6.1%) patients, respectively. In eRA versus ePsA, enthesitis of MFC was more frequently found (16 (48.4%) and 8 (22.2%) patients), respectively. Ultrasound revealed no significant differences between the groups in enthesitis. In ePsA, there was a significant correlation between DAS, DAS28, SDAI, CDAI, LEI, and LEI+PF.Conclusion. Enthesis ultrasound cannot differentiate ePsA from eRA. Clinical examination more frequently detects enthesitis in the knee joints in eRA and in the calcaneal region in ePsA

THE DIAGNOSTIC VALUE OF CLINICAL EXAMINATION AND ULTRASOUND STUDY OF ENTHESES FOR EARLY DETECTION OF PSORIATIC AND RHEUMATOID ARTHRITIS: REMARC STUDY

The diagnosis of enthesitis can help in differentiating early psoriatic arthritis (ePsA) from early rheumatoid arthritis (eRA).Objective. To estimate the diagnostic value of detecting enthesitis during clinical examination and ultrasound in ePsA and eRA.Subjects and methods. The trial included 36 patients with ePsA and 33 with eRA. Entheses were evaluated using the Leeds Enthesitis Index (LEI): lateral humeral epicondyle and medial femoral condyle (MFC), Achilles tendon insertion site (ATAP), and plantar fascia (PF) point on the right and on the left. Enthesitis (on ultrasound) presented with thickening, reduced echo density, and vascularization at Doppler energy imaging. DAS, DAS28, SDAI, CDAI, M±SD, Me [25th, 75th percentile], t-test, Fisher's exact test, χ2test, U test, and Spearman correlation coefficients (R) were calculated; the value p &lt; 0.05 was considered statistically significant.Results. Clinical examination revealed enthesitis in 41.6% of the patients with ePsA and in 39.4% of those with eRA (p &gt;0.05). No significant differences were found between ePsA and eRA according to LEI (0.5 [0; 2] and 1 [0; 2] and to LEI+PF (1 [0; 2] and 1 [0; 2], respectively). Enthesitis of MFC and PF was significantly more frequently detected in ePsA than in eRA – 12 (33.3%)/2 (6.1%) and 10 (27.8%)/2 (6.1%) patients, respectively. In eRA versus ePsA, enthesitis of MFC was more frequently found (16 (48.4%) and 8 (22.2%) patients), respectively. Ultrasound revealed no significant differences between the groups in enthesitis. In ePsA, there was a significant correlation between DAS, DAS28, SDAI, CDAI, LEI, and LEI+PF.Conclusion. Enthesis ultrasound cannot differentiate ePsA from eRA. Clinical examination more frequently detects enthesitis in the knee joints in eRA and in the calcaneal region in ePsA

Persistence and effectiveness of the IL-12/23 pathway inhibitor ustekinumab or tumour necrosis factor inhibitor treatment in patients with psoriatic arthritis: 1-year results from the real-world PsABio Study

Objective: We evaluated real-world treatment persistence and effectiveness at 1 year following initiation of IL-12/23 inhibitor ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis (PsA). Methods: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or TNFi. Drug persistence, effectiveness (achievement of clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very low disease activity (MDA/VLDA)), and safety were assessed every 6 months. In addition to descriptive statistics, propensity score (PS)-adjusted comparisons across cohorts were performed. Results: At 1 year, overall persistence was similar in the ustekinumab (n=317/438, 72.4%) and TNFi (n=321/455, 70.5%) groups. PS-adjusted HR (95% CI) for stopping/switching ustekinumab versus TNFi was 0.82 (0.60; 1.13). cDAPSA LDA (including remission)/remission was achieved in 55.9%/22.1% of ustekinumab-treated and 67.1%/31.7% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.80 (0.57; 1.10) for cDAPSA LDA and 0.73 (0.49; 1.07) for remission. MDA/VLDA was achieved in 34.2%/11.9% of ustekinumab-treated and 43.1%/12.6% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63; 1.26) for MDA and 0.90 (0.54; 1.49) for VLDA. The safety profiles were similar in both groups. Conclusion: In the real-world PsABio Study, after 1 year of treatment, although unadjusted persistence was numerically slightly higher for ustekinumab versus TNFi and unadjusted effectiveness was numerically slightly higher for TNFi versus ustekinumab, the PS-adjusted comparisons demonstrated comparable overall persistence, effectiveness and safety for both modes of action in PsA

Persistence and effectiveness of the IL-12/23 pathway inhibitor ustekinumab or tumour necrosis factor inhibitor treatment in patients with psoriatic arthritis: 1-year results from the real-world PsABio Study.

OBJECTIVE: We evaluated real-world treatment persistence and effectiveness at 1 year following initiation of IL-12/23 inhibitor ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis (PsA). METHODS: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or TNFi. Drug persistence, effectiveness (achievement of clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very low disease activity (MDA/VLDA)), and safety were assessed every 6 months. In addition to descriptive statistics, propensity score (PS)-adjusted comparisons across cohorts were performed. RESULTS: At 1 year, overall persistence was similar in the ustekinumab (n=317/438, 72.4\%) and TNFi (n=321/455, 70.5\%) groups. PS-adjusted HR (95\% CI) for stopping/switching ustekinumab versus TNFi was 0.82 (0.60; 1.13). cDAPSA LDA (including remission)/remission was achieved in 55.9\%/22.1\% of ustekinumab-treated and 67.1\%/31.7\% of TNFi-treated patients; PS-adjusted ORs (95\% CI) were 0.80 (0.57; 1.10) for cDAPSA LDA and 0.73 (0.49; 1.07) for remission. MDA/VLDA was achieved in 34.2\%/11.9\% of ustekinumab-treated and 43.1\%/12.6\% of TNFi-treated patients; PS-adjusted ORs (95\% CI) were 0.89 (0.63; 1.26) for MDA and 0.90 (0.54; 1.49) for VLDA. The safety profiles were similar in both groups. CONCLUSION: In the real-world PsABio Study, after 1 year of treatment, although unadjusted persistence was numerically slightly higher for ustekinumab versus TNFi and unadjusted effectiveness was numerically slightly higher for TNFi versus ustekinumab, the PS-adjusted comparisons demonstrated comparable overall persistence, effectiveness and safety for both modes of action in PsA