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

Golimumab in the treatment of psoriatic arthritis: efficacy and safety

Tumor necrosis factor-α (TNF-α) holds a central position in the pathogenesis of autoimmune inflammatory diseases of the locomotor apparatus. A separate class of drugs, namely, TNF-α inhibitors, that are effective against multicomponent diseases, such as psoriatic arthritis (PsA), is now available to physicians. The paper reviews the results of clinical trials of the TNF-α inhibitor golimumab, a human TNF-α monoclonal antibody. Golimumab exerts a positive effect on all manifestations of PsA: arthritis, psoriatic skin and nail lesions, dactylitis, enthesitis, and quality of life. The drug is noted for its convenient route of administration – its standard dose is 50 mg injected subcutaneously once a month and for its low molecular immunogenicity. Recent data suggest that golimumab is an effective drug with a safety profile similar to that of the entire class of TNF-α inhibitors

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