Clinical Manifestations Of Psoriatic Arthritis Research Articles

Efficacy of tofacitinib in psoriatic arthritis: literature review and case report

The article presents the results of a search in the PubMed and Google Scholar databases (meta-analyses, systematic reviews, clinical trials and case studies) evaluating the treatment of PsA with tofacitinib (TOFA). The review contains the most up-to-date information about the efficacy and safety of TOFA, a drug from the group of janus kinase inhibitors (JAKi), a brief description of the mechanism of action of TOFA is given, with mention of blocked signaling intracellular pathways. The spectrum of “key” clinical manifestations of psoriatic arthritis (PsA) is described, in which the therapeutic potential of TOFA (peripheral arthritis, psoriasis, enthesitis and dactylitis) is most fully revealed. The results of the main randomized controlled trials (OPAL Broaden and OPAL Beyond), postmarketing trials, descriptive studies and clinical observations are considered, and the high efficacy of TOFA for the treatment of PsA patients who did not respond to therapy with synthetic disease-modifying drugs and/ or Tumor Necrosis Factor inhibitors (TNFi) is demonstrated. The results (and their interpretation) of studying the safety of long-term use of different doses of TOFA – 5 mg 2 times a day and 10 mg 2 times a day and retention (“survival”) are presented therapy, with an emphasis on adverse events of special interest (“large” cardiological events (MACE), oncologics, infections). The results of treatment with tofacitinib in patients with PsA according to the All-Russian register of patients are presented. The pronounced positive effect of TOFA on the parameters that are defined as “patient-reported outcome – PRO” is particularly emphasized: indicators of fatigue, self-assessment, patient’s assessment of his condition according to VAS, assessment by HAQ-DI (Health Assessment Questionnaire), SF-36 (non-specific questionnaire for quality assessment patient’s life), etc. A clinical observation is presented that demonstrates a vivid therapeutic effect on arthritis, enteritis, dactylitis, clinical signs of spondylitis, sacroiliitis, as well as the skin process in a patient with active PsA.

New Insights into Pathogenesis, Diagnosis and Treatment of Psoriatic Arthritis

Introduction: Psoriatic Arthritis (PSA) is an inflammatory musculoskeletal disorder characterized by significant dysfunction in synovial tissue, tendons and axial sites. PSA is associated with metabolic comorbidities such as diabetes, obesity, congestive heart failure, fatty liver disease, depression and/or anxiety. Due to differences in the clinical manifestations of PSA, some patients are not diagnosed through clinical examination. Delayed psoriatic arthritis diagnosis or consultation has been related to low quality of life and increased frequency of comorbidities and persistent inflammatory state. The aim of the present study was to explore multiple etiologies of PSA, screening tools, and pharmaceutical therapy. Articles were searched from international databases including Magiran, Scopus, Google Scholar, PubMed, and Springer. The keywords of Psoriatic Arthritis, Screening tools, pathogenesis, treatment, and Biomarkers were used to extract articles.
 Conclusion: Our study showed that heterogeneity in the etiology of PSA was a major reason for classification problems within this disease spectrum. The explanation for this disease heterogeneity may be focused on variations in genetic and environmental factors. Screening strategies (ex: CASPAR criteria and biomarkers) are a significant first step in early treatment. Moreover, many types of therapy are available to help decreased joint problems, muscle weakness, and disease severity. Detection of dependent factors related to PSA might help in the early intervention of these patients to address clinical and para-clinical issues.
 Here we have provided an updated review of the early diagnosis, clinical features, pathogenesis, screening tools, biomarkers, and treatment recommendations, such as new biologic medications, for Psoriatic Arthritis.

The role of the traumatic factor and isomorphic reaction in the early diagnosis of psoriatic arthritis

Rationale: Evaluation of the role of the deep Koebner's phenomenon and traumatization seems to be a promising direction in the search of the solution for the delayed diagnosis of psoriatic arthritis (PsA) in patients with psoriasis. We have put forward the question if joint and ligament abnormalities induced by a trauma or persistent physical activity could be an analogue of the skin isomorphic reaction in psoriasis.
 Aim: To identify joint and ligament abnormalities in patients with psoriasis caused by mechanical stress and their association with the deep Koebner's phenomenon and PsA.
 Materials and methods: This was an open-label, non-randomized, comparative study in parallel groups in 80 in-patients with psoriasis (recruited in the Dermatovenereological clinic № 1, Ufa); the control group included 80 in-patients with PsA. All patients were assessed by a dermatovenereologist, including past history, severity of psoriasis, degree of PsA activity, special questionnaires and the presence of an isomorphic reaction in the skin and periarticular tissues. The joints with maximal physical activity were assessed by X-ray. PsA was diagnosed by a rheumatologist.
 Results: The patients from both groups were matched in terms of age, gender, and duration of psoriasis. Pain, joint stiffness and limitation of mobility were present not only in the PsA group, but also in the patients with psoriasis (35%, 27.5% and 26.2% of the patients, respectively). Despite most of the patients in the psoriasis group had no active complaints (65.0% vs. 0% in the control group, p 0.001), clinical signs of inflammation of the tendons and entheses and relevant history were found in 47.5% (68.7% in the control group, p = 0.007). Hand tendinitis was most prevalent symptom in both groups: 40.0% (32/80) in the psoriasis group and 63.7% (51/80) in the PsA group (p = 0.003). Achilles tendon lesions were found in 17.5% (14/80) and 52.5% (42/80) (p 0.001) and periarticular edema in 27.5% (22/80) and 63.7% (51/80), respectively (p 0.001). The combination of these signs with psoriatic plaques in this area was observed in 32.5% (26/80) and 92.5% (74/80) of the patients, respectively (p 0.001). The comparison of the clinical and X-ray data showed that 38 patients with psoriasis and newly diagnosed PsA had had an increased physical load on the affected joints, as well as signs of a deep isomorphic reaction (tendinitis, periarticular edema, or enthesitis near the involved joints). In both groups, the most common form of PsA was distal one (63.2% [24/38] of the patients with newly diagnosed PsA and 58.7% [47/80] of the patients with previously diagnosed PsA, p = 0.648).
 Conclusion: Involvement of the periarticular tissues, as well as early, including preclinical, X-ray abnormalities in the joints of patients with psoriasis can be associated with increased physical activity and the deep Koebner's phenomenon. Therefore, even if patients with psoriasis do not have any clinical manifestations of PsA and no complaints when seen by a dermatovenereologist, it is recommended to perform a detailed collection of past history data with clarification of the type of physical activity and past trauma, as well as to examine both by inspection and palpation the periarticular tissues (tendons and entheses), for the timely use of X-ray examination, consultation of a rheumatologist aimed at diagnosis of psoriatic arthritis.

Axial involvement in psoriatic arthritis

Among the variety of clinical manifestations of psoriatic arthritis (PsA) – including peripheral arthritis, dactylitis, enthesitis, and axial disease – spondylitis is the least studied. There is no generally accepted definition of axial PsA (axPsA), nor is there any common terminology or diagnostic criteria for it. In the rheumatology community, there is also no consensus regarding radiological and MRI assessment of axial involvement in PsA patients, while disease activity indexes and the therapeutic tactics are borrowed from those used in treating axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS). However, despite a range of similarities in immunopathogenetic mechanisms of axPsA and axSpA, there are also certain differences that may affect the treatment response in these patients. The aim of this review is the analysis of data on axial disease in PsA. The article discusses the genetic features, clinical presentations, imaging techniques, differential diagnostics and treatment options of axPsA.

DNA methylation markers in peripheral blood for psoriatic arthritis

BackgroundThe clinical manifestations of psoriatic arthritis (PsA) are highly heterogeneous and no reliable diagnostic biomarkers exist. ObjectiveWe explored the role of DNA methylation CpG markers in the diagnosis of PsA. MethodsDNA methylation array was used to screen for differentially methylated sites (DMSs) in the discovery phase (PsA, n = 25; healthy controls [HCs], n = 19; psoriasis vulgaris [PsV], n = 20). In the validation phase, pyrosequencing was used to identify the DMSs in an expanded cohort (PsA, n = 60; HCs, n = 91; PsV, n = 48; rheumatoid arthritis [RA], n = 60). Logistic regression prediction models were established based on the identified DMSs for the diagnosis of PsA. ResultsA total of 17 DMSs differentiating PsA and HCs as well as 11 DMSs differentiating PsA and PsV were screened in the discovery phase. A total of six DMSs (chr14: cg07940072, chr14: 38061320, chr9: cg15734589, chr6: cg12800266, chr3: cg12992827, chr6: cg24500972) differentiating PsA and HCs and two DMSs (chr12: cg16459382, chr2: cg16348668) differentiating PsA and PsV were identified using pyrosequencing. Three logistic regression prediction models were established based on the identified DMSs, which distinguished PsA, RA, PsV, and HCs (P < 0.001). The models performed well in differentiating PsA from HCs, RA, and PsV (AUC: 0.858, 0.851, and 0.976, respectively). ConclusionsThe models based on methylated CpG sites are useful for distinguishing patients with PsA from HCs and those with RA or PsV and are a highly sensitive and specific diagnostic biomarker for PsA.

The Effect of Ketogenic Diet on Inflammatory Arthritis and Cardiovascular Health in Rheumatic Conditions: A Mini Review.

The principle of ketogenic diet (KD) is restriction of carbohydrates to a maximum of 5–10% of the total daily caloric intake, aiming at shifting body metabolism toward ketone bodies. Different studies suggested promising results of KD to help patients to lose weight, to reduce insulin requirements in diabetes, to supplement cancer protocols, to treat neurological conditions and to optimize control of metabolic and cardiovascular diseases. However, literature about the anti-inflammatory properties of KD in rheumatic diseases is still limited. The beneficial effects of weight loss in patients with inflammatory arthritis can be explained by biomechanical and biochemical factors. Obesity is associated with macrophage activation and production of pro-inflammatory cytokines including TNF-α, IL-1b, and IL-6. The clinical effect of KD may be primarily attributed to improvement of insulin sensitivity. Insulin resistance is associated with an increase of TNF-α, IL-1α, IL-1β, IL-6, and leptin. Moreover, reduction of body's adipose tissue and weight loss account for part of the anti-inflammatory effects and for the impact of KD on cardiovascular health. In rheumatoid arthritis, fasting was shown to be effective in reducing disease symptoms, possibly through the production of β-hydroxybutyrate (BHB), the main ketone body. BHB may exert inhibitory effects also on IL-17 and intermittent fasting improved the clinical manifestations of psoriatic arthritis. In ankylosing spondylitis, current literature doesn't allow to draw conclusion about the effects of KD. Future prospective studies will be needed to elucidate the potential beneficial effects of KD on specific domains and clinical outcomes in patients with inflammatory arthritis.

Hyperuricemia in Psoriatic Arthritis: Epidemiology, Pathophysiology, and Clinical Implications.

Psoriatic arthritis (PsA) represents the articular component of the systemic psoriatic disease and the extra-cutaneous disorder most frequently found in patients with psoriasis. Besides the articular involvement, PsA is associated with several metabolic abnormalities such as insulin resistance, hypertension, diabetes and hyperuricemia. Uric acid is the final product of purine metabolism and the etiological substrate of gout. Accumulating evidence highlights the emerging role of hyperuricemia as a major cardiovascular risk factor. Moreover, different studies evaluated the interplay between hyperuricemia and psoriatic disease, suggesting that individuals affected by psoriasis or PsA might present higher serum levels of uric acid and that hyperuricemia might affect severity of clinical manifestations and degree of inflammation in PsA patients. In this review, we focus on the bidirectional relationship between uric acid and PsA, analyzing how uric acid may be involved in the pathogenesis of psoriasis/PsA and how clinical manifestations of PsA and inflammatory mediators are affected by uric acid concentrations. Finally, the effects of anti-rheumatic drugs on uric acid levels and the potential benefit of urate-lowering therapies on psoriasis and PsA were summarized.

Comparative efficacy of tofacitinib and adalimumab in patients with psoriatic arthritis in real clinical practice. Data from the Russian nationwide register of patients with psoriatic arthritis

Objective: to compare the clinical efficacy in real clinical practice of the targeted synthetic disease-modifying antirheumatic drug (sDMARD) tofacitinib (TOFA) and the biologic DMARD (bDMARD), an inhibitor of tumor necrosis factor alpha (TNFα), adalimumab (ADA) in patients with psoriatic arthritis (PsA), included in the Russian nationwide register of patients with PsA.Patients and methods. The study included 77 patients with PsA (43 men and 34 women) who met the CASPAR criteria and were observed in the Russian nationwide register. Patients were divided into two groups depending on the treatment. Group 1, in which oral TOFA was prescribed, 5 mg 2 times a day, included 41 patients: 24 (58.5%) men and 17 (41.5%) women, the median age was 41 [34; 50] years, the median duration of PsA was 72 [35; 120] months. Group 2, in which subcutaneous ADA was used, 40 mg every 2 weeks, included 36 patients: 19 (52.8%) men and 17 (47.2%) women, the median age was 44 [34; 51] years, the median duration of PsA was 59 [22; 102] months. Combination therapy, including methotrexate (MT), received 80.5% of patients in the TOFA group and 52.8% of patients in the ADA group. At the beginning of the study and every 6 months further, the activity and efficacy of PsA therapy were assessed in all patients according to DAPSA and criteria for minimal disease activity – MDA (number of painful joints ≤1, number of swollen joints ≤1, PASI ≤1 or BSA ≤3 , pain score ≤15, patient's general assessment of disease activity ≤20 mm on a visual analogue scale, HAQ ≤0.5, enthesitis ≤1), dynamics of BASDAI and BSA were also assessed. The number of patients who achieved remission (DAPSA ≤4) or MDA (5 criteria out of 7) during therapy with TOFA and ADA was determined.Results and discussion. Before the start of the therapy in the 1st group, the median DAPSA was 44.2 [37.8; 55.3]: moderate PsA activity was in 5 (12.2%) patients, high in 36 (87.8%) patients. In group 2, the median DAPSA was 35.8 [21.1; 52]: low activity was detected in 3 (8.6%), moderate – in 11 (31.4%), high – in 21 (60%) patients (data from 35 patients was available). 6 months after the start of treatment in patients of the 1st and the 2nd group, there was a significant decrease in all indicators of PsA activity compared to the baseline. The median DAPSA was 11 [4.3; 17.3] and 9.1 [6; 19.6]; remissions according to DAPSA reached 11 (26.8%) and 6 (20.8%) patients, respectively, low activity – 15 (36.6%) and 13 (44.8%), MDA – 16 (40%) and 9 (30%). The number of patients with dactylitis in the 1st and in the 2nd group significantly decreased: from 22 (53.7%) to 5 (13.2%) and from 13 (36.1%) to 6 (20%), respectively. Median HAQ decreased from 1 [0.625; 1.5] to 0.5 [0; 0.875] and from 0.875 [0.5; 1.38] to 0.5 [0; 0.875]; median BASDAI – from 6 [4.2; 7] to 1.4 [0.6; 3.2] and from 4.4 [1.9; 5.8] to 3 [0.8; 4.5], respectively. In group 1, the number of patients with BSA&gt; 3% decreased from 16 (39%) to 8 (26.7%; p&lt;0.225), and in group 2, due to insufficient data (5 patients), we failed to evaluate BSA dynamics.Conclusion. In real clinical practice TOFA and ADA both had comparable efficacy on all clinical manifestations of PsA: after 6 months of therapy, most patients with PsA achieved MDA, low disease activity and remission according to DAPSA and BASDAI.

EFFICACY AND SAFETY OF TOFACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS IN REAL CLINICAL PRACTICE

Objective: to evaluate the clinical efficacy and safety of the targeted synthetic disease-modifying anti-rheumatic drug (DMARD) tofacitinib (TOFA; Yakvinus®) in patients with active psoriatic arthritis (PsA) at 12 and 24 weeks after starting treatment. To define the place of TOFA in the therapy of PsA patients. Subjects and methods. Examinations were made in 41 patients (17 men and 24 women) with active PsA and an insufficient response to previous treatment with synthetic DMARDs and/or biological agents (BA). Before starting therapy, the median disease activity for psoriatic arthritis (DAPSA) and disease activity score (DAS28) were 44.2 [37.8; 55.3] and 5.5 [4.7; 6.1], respectively. TOFA tablets were prescribed at a dose of 5 mg twice daily for 24 weeks with possible dose escalation to 10 mg twice daily after 12 weeks. At the beginning of the investigation, at 12 and 24 weeks, the investigators assessed disease activity and TOFA therapy efficiency of according to DAPSA, DAS28 and minimal disease activity (MDA) criteria: tender joint count ≤1, swollen joint count ≤1, a psoriasis area severity index (PASI) ≤1 or body surface area (BSA) ≤3%, pain intensity ≤15 mm, patient global assessment ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, and enthesitis ≤1. They also determined the number of patients who had achieved remission (DAPSA ≤4, DAS28 score &lt;2.6), low disease activity (DAPSA 5-14, ≤2.6, DAS28 &lt;3.2) or MDA (5 out of the 7 criteria) during TOFA therapy at 24-week follow-up. The safety of therapy was evaluated by analyzing the drug-induced adverse events (AE): the frequency, severity and time of their occurrence were studied. Results and discussion. At 24 weeks after initiation of TOFA therapy, there was a significant decrease of median DAPSA and DAS28 values as compared to baseline, to 11 [4.3; 17.3] and 2.6 [1.7; 3.4] respectively. The median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) also significantly decreased from 6 [4.2; 7] and 3.8 [2.8; 4.4] to 1.4 [0.6; 3.2] and 1.5 [1; 2.1] respectively. The median BSA was significantly reduced from 3 [1; 5] to 0.5 [0.1; 2]. At 24 weeks after initiation of TOFA therapy, DAPSA and DAS28 low disease activity/remission were achieved by 38.5/23.1% and 17.9/53.9% of patients, respectively. Fifteen (38.5%) patients achieved MDA. 38 (92.7%) of the 41 patients completed a full TOFA therapy cycle. Two patients dropped out of the investigation due to ineffective therapy and one due to AE (diarrhea occurring up to 10 times daily, headache, elevated blood pressure, and lacrimation). At 24 weeks, 14 (34.2%) patients reported to have AE. The most common AE noted in 7 (17.1%) patients were infections: acute respiratory viral infection (n=3), fever (n=2), and folliculitis (n=2). In addition, two patients had diarrhea and two had headache. Conclusion. TOFA is an effective drug for the treatment of PsA patients with moderate or high inflammatory activity, has a significant effect on all clinical manifestations of PsA and has a satisfactory safety profile.

Role of TNF-Alpha and IL10 genes in the development and clinical manifestations of psoriatic arthritis

ObjectiveTo evaluate the impact of polymorphisms of TNF-alpha (TNFA) and IL10 genes and their association with clinical phenotypes of psoriatic arthritis (PsA). Materials and methodsThe study included 104 unrelated Venezuelan individuals, grouped into 52 patients with PsA, who fulfilled the CASPAR criteria, and 52 healthy individuals with no family history of psoriasis. The polymorphisms of the TNFA and IL10 genes were determined by Single Specific Primer-Polymerase Chain Reaction (SSP-PCR). ResultsThe GA genotype and A allele of the TNFA-238G/A polymorphism appears to confer protection against the development of PsA (OR: 0.31, 95% CI: 0.92–1.05, p=0.02). The GA genotype of the TNFA-308G/A polymorphism is associated with a late onset age of PsA (GA=60±13.17 years vs. GG=43.55±14.29 years, p=0.002), and the GG genotype of the IL10 -1082A/G polymorphism with a longer time interval between the onset of psoriasis and the development of PsA (GG=27.4±24.11 years, GA=5.47±7.23 years, AA=7.86±8.51 years, p=0.001). The CC genotypes of IL10-819 C/T and IL10-592 C/A confer risk of damage to distal interphalangeal joints (OR: 4.79, p=0.026). ConclusionsThe TNFA-238G/A polymorphism plays an important role in the development of PsA in mixed-race Venezuelans. Likewise, TNFA-308 G/A, IL10 -1082 A/G, -819C/T, -592C/A polymorphisms may modify the clinical expression of PsA.

Use of the interleukin-17A inhibitor secukinumab in psoriatic arthritis: a subanalysis of the Russian population in the international randomized clinical trials FUTURE 1 and FUTURE 2

The investigators carried out an analysis of the efficacy and safety of secukinumab (SEC) in the randomized placebocontrolled trials (RPCTs) FUTURE 1 and FUTURE 2, as well as a subanalysis of the data obtained in the Russian population of patients with active psoriatic arthritis (PsA). The FUTURE 1 and FUTURE 2 trials enrolled a total of 1003 patients with active PsA. They received SEC (n = 703) or placebo (PL) (n = 300). The use of SEC 300 or 150 mg without previous intravenous (IV) loading dose or either 150 or 75 mg with the IV loading dose led to a significant improvement in patients with PsA. The positive changes in the main clinical manifestations of PsA at 24 weeks persisted until 52 weeks of therapy. SEC was effective in both the patients who had not previously received tumor necrosis factor-α inhibitors and those who had previously taken these drugs, and the result of therapy did not depend on concomitant methotrexate use.The incidence of cancer was low and comparable in the SEC and PL groups. Analysis of the combined data on the safety of the two RPCTs showed that the treatment duration-adjusted incidence of malignant neoplasms was 0.5 per 100 patient-years in the SEC groups and 0.9 in the PL groups. The safety profile of SEC in these RPCTs corresponds to that in the previous studies of the drug.The data from the pooled analysis of the Russian subpopulation of patients with PsA fully agree with the results obtained in the evaluation of all the patients included in FUTURE 1 and FUTURE 2 and confirm the most important role of IL-17А in the pathogenesis of PsA.

Comparative characterization of the data of magnetic resonance imaging, X-ray and clinical studies of the hand and foot joints in patients with early psoriatic arthritis

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Classification and clinical assessment

There are at least nine classification criteria for psoriatic arthritis (PsA) that have been proposed and used in clinical studies. With the exception of the ESSG and Bennett rules, all of the other criteria sets have a good performance in identifying PsA patients. As the CASPAR criteria are based on a robust study methodology, they are considered the current reference standard. However, if there seems to be no doubt that they are very good to classify PsA patients (very high specificity), they might be not sensitive enough to diagnose patients with unknown early PsA. The vast clinical heterogeneity of PsA makes its assessment very challenging. Peripheral joint involvement is measured by 78/76 joint counts, spine involvement by the instruments used for ankylosing spondylitis (AS), dactylitis by involved digit count or by the Leeds dactylitis index, enthesitis by the number of affected entheses (several indices available) and psoriasis by the Psoriasis Area and Severity Index (PASI). Peripheral joint damage can be assessed by a modified van der Heijde-Sharp scoring system and axial damage by the methods used for AS or by the Psoriatic Arthritis Spondylitis Radiology Index (PASRI). As in other arthritides, global evaluation of disease activity and severity by patient and physician and assessment of disability and quality of life are widely used. Finally, composite indices that capture several clinical manifestations of PsA have been proposed and a new instrument, the Psoriatic ARthritis Disease Activity Score (PASDAS), is currently being developed.

Anti-TNF-α agents in the treatment of psoriatic arthritis

Psoriatic arthritis (PsA) is a potentially debilitating disease that may affect small and large peripheral joints, entheses and the axial skeleton. The different clinical manifestations of PsA have been accounted for by various proposals of subdividing the patients into different subgroups. According to the predominant clinical symptoms, most patients can be classified as belonging to the spectrum of spondyloarthritides (SpA) or rheumatoid arthritis (RA). The conventional therapeutic approach comprises non-steroidal anti-inflammatory drugs, systemic and intra-articular corticosteroids, and disease-modifying antirheumatic drugs such as sulfasalazine, methotrexate, ciclosporin and leflunomide. Similar to RA, recent trials in PsA have shown excellent results with the tumour necrosis factor (TNF) blockers etanercept, infliximab and adalimumab, which have positive effects not only on joints, but also on the skin when affected by psoriasis, quality of life, function and slowing of disease progress, as evidenced radiologically. Anti-TNF therapy has been generally safe in clinical trials of PsA. Taken together, there has been definite recent progress in the treatment of PsA, especially for severely affected patients.