Treatment Of Psoriatic Arthritis Research Articles

Multi-modality data-driven analysis of diagnosis and treatment of psoriatic arthritis

Psoriatic arthritis (PsA) is associated with psoriasis, featured by its irreversible joint symptoms. Despite the significant impact on the healthcare system, it is still challenging to leverage machine learning or statistical models to predict PsA and its progression, or analyze drug efficacy. With 3961 patients’ clinical records, we developed a machine learning model for PsA diagnosis and analysis of PsA progression risk, respectively. Furthermore, general additive models (GAMs) and the Kaplan–Meier (KM) method were applied to analyze the efficacy of various drugs on psoriasis treatment and inhibiting PsA progression. The independent experiment on the PsA prediction model demonstrates outstanding prediction performance with an AUC score of 0.87 and an AUPR score of 0.89, and the Jackknife validation test on the PsA progression prediction model also suggests the superior performance with an AUC score of 0.80 and an AUPR score of 0.83, respectively. We also identified that interleukin-17 inhibitors were the more effective drug for severe psoriasis compared to other drugs, and methotrexate had a lower effect in inhibiting PsA progression. The results demonstrate that machine learning and statistical approaches enable accurate early prediction of PsA and its progression, and analysis of drug efficacy.

Long-Term Efficacy, Safety, and Drug Survival of Guselkumab in Patients with Psoriasis: Real-World Data from the Czech Republic BIOREP Registry.

Real-world data on the long-term use of guselkumab for treatment of psoriasis are still limited. We aimed to evaluate long-term efficacy, safety, and drug survival of guselkumab in a real-world setting. This is a retrospective study analyzing Czech Republic registry (BIOREP) data of patients treated with guselkumab. In total, 333 patients were included. Improvement in Psoriasis Area and Severity Index (PASI) score was significant. Mean PASI score decreased from 16 at baseline to 0.7, 0.9, and 0.8 after 12, 24, and 36months, respectively. Absolute PASI scores of ≤ 3 and ≤ 1 were achieved in 93.9% and 77.9%, 94.2% and 71.0%, and 94.8% and 70.7% of patients after 12, 24, and 36months, respectively. Response PASI 90 and PASI 100 were attained in 81.8% and 57.1%, 75.4% and 50.7%, and 75.9% and 55.2% of patients after 12, 24, and 36months, respectively. The percentage of patients achieving PASI 90 and PASI 100 responses was higher throughout the study in bio-naive and in normal-weight patients, while presence of psoriatic arthritis had no influence. Improvement in Dermatology Life Quality Index (DLQI) score was also significant; mean DLQI score decreased from 14.2 at baseline to 0.9, 1.0, and 0.7 after 12, 24, and 36months, respectively. Patients with PASI 100 had lower mean DLQI throughout the study compared with patients with PASI 90. Major reason for discontinuation was loss of effectiveness in 7.1% of patients, while only 0.6% were due to adverse events. Overall cumulative drug survival was high, with only a minimal decline over time, reaching 91.6%, 87.0%, and 85.5% after 12, 24, and 36months, respectively. Drug survival was not affected by previous biological treatment, patient weight, or presence of psoriatic arthritis. This real-world study demonstrated the long-term effectiveness, good safety profile, and high drug survival of guselkumab treatment over a period of 36months.

Adverse events associated with anti-IL-17 agents for psoriasis and psoriatic arthritis: a systematic scoping review.

Anti-interleukin (IL)-17 biological agents (BAs) have significant efficacy in the treatment of psoriasis and psoriatic arthritis; however, adverse events (AEs) are common, and their safety has not been systematically evaluated. The purpose of this systematic review and meta-analysis was to summarize the number and corresponding rates of AEs caused by anti-IL-17 BAs in patients with psoriasis and psoriatic arthritis to improve clinical decision-making regarding their use. PubMed, Embase, Cochrane Library, and Web of Science databases were independently searched by three authors for articles on the treatment of psoriasis with anti-IL-17 BAs that were published before March 1, 2022, and included at least one AE. Dichotomous variables and 95% confidence intervals (CI) were analyzed using R software (version 4.1.3) and the Meta and Metafor software packages. Funnel plots and meta-regression were used to test for the risk of bias, I2 was used to assess the magnitude of heterogeneity, and subgroup analysis was used to reduce heterogeneity. A total of 57 studies involving 28,424 patients with psoriasis treated with anti-IL-17 BAs were included in the meta-analysis. Subgroup analysis showed that anti-IL-17A (73.48%) and anti-IL-17A/F (73.12%) BAs were more likely to cause AEs than anti-IL-17R BAs (65.66%). The incidence of AEs was as high as 72.70% with treatment durations longer than one year, and long-term use of medication had the potential to lead to mental disorders. Infection (33.16%), nasopharyngitis (13.74%), and injection site reactions (8.28%) were the most common AEs. Anti-IL-17 BAs were most likely to cause type α (33.52%) AEs. Type δ AEs (1.01%) were rarely observed. Anti-IL-17 BAs used for the treatment of psoriasis and psoriatic arthritis caused a series of AEs, but the symptoms were generally mild.

A critical review of upadacitinib for the treatment of adults with moderately to severely active ulcerative colitis

ABSTRACT Introduction Upadacitinib is a selective janus kinase 1 inhibitor. In March 2022, upadacitinib was approved by the US Food and Drug Administration for the management of moderately to severely active ulcerative colitis (UC) in those who have had an inadequate response or intolerance of tumor necrosis factor inhibitors. It is also approved for the treatment of psoriatic arthritis, atopic dermatitis, rheumatoid arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis. Areas Covered The aim of this article is to review the mechanism of action of upadacitinib, clinical data regarding its efficacy in treating UC, and safety information. Expert Opinion Upadacitinib is superior to placebo in inducing and maintaining both clinical and endoscopic remission in moderately to severely active UC. Its strengths include once daily oral route of administration, low risk of immunogenicity, rapid onset, and efficacy in patients with previous failure of biologic therapy. The use of upadacitinib has been limited due to safety concerns surrounding JAK inhibitors. Phase 3 clinical trials recorded more cases of herpes zoster infection and venous thromboembolism in patients with UC treated with upadacitinib compared to placebo. Ongoing long-term safety studies will provide much needed clarity. Further research is also required to define the positioning of upadacitinib in treatment algorithms.

Treatment Retention and Safety of Ixekizumab in Psoriatic Arthritis: A Real Life Single-Center Experience.

Information on the performance of ixekizumab (IXE) in patients with psoriatic arthritis (PsA) in clinical practice is scarce. We aimed to analyze the retention rate and safety of IXE in patients with PsA in routine clinical practice. A retrospective longitudinal observational single-center study of all patients with PsA who had received at least one dose of IXE. Adverse events (AEs) and drug retention rate were the main study focus. Survival was analyzed using Kaplan-Meier curves and predictive factors using multivariate Cox regression analysis. The hazard ratio (HR) was used as a measure of the association. Seventy-two patients were included (52 women and 20 men). Median disease duration was 5 years (IQR 3-9). More than 90% received ≥2 biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) prior to IXE. Ixekizumab showed a 1-year retention rate of 65% and a 2-year retention rate of 57%. Regarding discontinuation due to AEs, 0.18 AEs per person-year were identified. The number of previous biologics did not influence drug survival but prior use of methotrexate (HR 2.31 (95% CI 1.05-5.10), p < 0.05) and depression (HR 2.40 (95% CI 1.07-5.41), p < 0.05) increased the risk of IXE discontinuation. Ixekizumab showed a good retention rate in a PsA population mostly refractory to biologic and targeted synthetic DMARDs. Drug survival was consistently good regardless of age, gender, metabolic comorbidities, smoking status, or prior number of biologic therapies. This information may be of interest to better position this drug in the PsA treatment algorithms.

Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors.

Plaque psoriasis is a systemic immune-mediated disease driven by interleukin-17 producing cells under the regulation of interleukin-23. Interleukin-23 signaling is mediated by the intracellular kinase tyrosine kinase 2, a Janus kinase family member. Tyrosine kinase 2 is a potential target for oral small-molecule therapies to treat psoriasis and psoriatic arthritis. A number of tyrosine kinase 2 inhibitors are in development or approved for the treatment of psoriasis or psoriatic arthritis. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved by the US Food and Drug Administration as a first-in-class treatment for adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy, and is approved by Pharmaceuticals and Medical Devices Agency (PDMA) in Japan for patients with plaque psoriasis, generalized pustular psoriasis, and erythrodermic psoriasis who have had an inadequate response to conventional therapies. Deucravacitinib selectively binds to the unique tyrosine kinase 2 regulatory pseudokinase domain in an allosteric fashion, preventing a conformational change in the catalytic domain required for ATP substrate binding, thus effectively locking tyrosine kinase 2 in an inactive state. Two other tyrosine kinase 2 inhibitors in later stage clinical development, brepocitinib (PF-06700841) and ropsacitinib (PF-06826647), are orthosteric inhibitors that target the highly conserved catalytic domain. This selective allosteric tyrosine kinase 2 inhibition may explain the improved safety profile of deucravacitinib versus orthosteric Janus kinase and tyrosine kinase 2 inhibitors. Two phase 3 psoriasis trials demonstrated deucravacitinib was efficacious and not associated with safety concerns characteristic of Janus kinase inhibitors, hence the new class designation (TYK2 inhibitor) by health authorities in the USA and Japan. Allosteric tyrosine kinase 2 inhibitors represent a promising new class of molecules for the treatment of psoriasis and psoriatic arthritis, and longer-term trials will establish their place in therapy.

The Amazing History of Methotrexate – 75 Years Later from its Discovery, Still the “Golden Standard” Therapy

"More than 75 years after its accidental discovery, methotrexate remains an important treatment option for many diseases. Whether it is various hematological and non-hematological neoplasms, rheumatological, dermatological, or other conditions, methotrexate remains in scope. For rheumatoid arthritis, current clinical guidelines (EULAR, ACR) recommend methotrexate as the first therapeutic option. This article aims to highlight important moments in the history of this remarkable drug, to review the literature on its mechanisms of action and the arguments for which after more than half a century, methotrexate remains the gold standard in the treatment of rheumatoid arthritis but also an important option for treatment of psoriasis vulgaris (PV) and psoriatic arthritis (PsA)."

Эффективность и безопасность иксекизумаба при лечении спондилоартритов в реальной клинической практике

Aim: to assess the efficacy and safety of ixekizumab in the treatment of ankylosing spondyloarthritis (AS) and psoriatic arthritis (PA) in real clinical practice. Patients and Methods: this retrospective study included patients with AS and PA who received ixekizumab therapy from February 2021 to April 2022. Disease activity was evaluated every 3–6 months, using BASDAI and ASDAS scores for AS and DAPSA и PASI scores for PA. C-reactive protein (CRP) served as a serologic marker of disease activity. Results: the analysis included the data received for 27 patients, of whom 10 persons had AS and 17 — PA. The safety of treatment was assessed in all patients, and the data of 9 AS and 16 PA patients were included in the analysis of the treatment efficacy. In the AS group (4 males and 5 females), the median age at the therapy initiation was 34 [32; 41.5] years and in the PA group (11 males and 6 females — 40 [32.5; 48.5] years. Failure or intolerance of the standard therapy was reported in all patients. Prior to ixekizumab treatment, most patients did not receive targeted therapies. Of 27 patients, 4 received genetically engineered biological drugs / targeted synthesized drugs which failed to achieve remission / low disease activity. In the AS group, the elevated levels of CRP were revealed in 7 (77.8%) patients, ASDAS demonstrated the presence of disease activity in all patients. According to BASDAI, disease activity was recorded in 7 (77.8%) cases. During the treatment, there was a downtrend in the percentage of patients with high disease activity as shown by ASDAS and BASDAI scores, as well as in the percentage of patients with elevated levels of CRP, while the BASDAI values were statistically significant (p=0.031). In the PA group, elevated CRP levels were reported in 62.5% of patients, and DAPSA scores represented moderate of high activity in 75.0% of patients. As a result of the treatment, there was a decrease in the percentage of patients with higher DAPSA scores and elevated CRP levels, but the changes did not achieve statistical significance. Side effects were reported in 7.4% of patients, but there were no serious adverse events. Conclusion: acording to our data ixekizumab has shown efficacy and safety in the treatment of PA and AS in real clinical practice. KEYWORDS: ixekizumab, real clinical practice, psoriatic arthritis, ankylosing spondyloarthritis, genetically engineered biological drugs. FOR CITATION: Meshkov A.D., Ostapenko V.S., Pykhtina V.S. The efficacy and safety of ixekizumab in the treatment of spondyloarthritis under the conditions of real clinical practice. Russian Medical Inquiry. 2023;7(3):137–143 (in Russ.). DOI: 10.32364/2587-6821- 2023-7-3-137-143.

Impact of psoriatic arthritis and comorbidities on ustekinumab outcomes in psoriasis: a retrospective, observational BADBIR cohort study

ObjectivesPsoriasis and psoriatic arthritis (PsA) are independently associated with comorbidities, including obesity and metabolic syndrome, which may impact treatment outcomes. This study aimed to assess baseline differences between patients with...

О важности междисциплинарного подхода в избирательном лечении псориаза и псориатического артрита

Psoriasis is one of the most common skin diseases. 30% of patients with psoriasis may develop psoriatic arthritis, which can lead to complex joint deformity and early disability. In this case, it is very important to have an interdisciplinary approach in the selective treatment of psoriasis and psoriatic arthritis using genetically engineered biological drugs. In our article, we present a world literature review on the use of genetically engineered biological drugs in psoriasis and psoriatic arthritis, describe a clinical case of psoriasis with psoriatic arthritis with effective basic treatment.

Bimekizumab, a Humanized Monoclonal Immunoglobulin G1 Antibody for the Treatment of Psoriatic Arthritis: A Systematic Review

Psoriatic arthritis (PsA), often accompanied by nail psoriasis, spine, enthesitis and iritis, is a typical complication of psoriasis. PsA leads to the destruction and/or ankylosis of the peripheral joints or spine, resulting in poor quality of life. Interleukin (IL)-23, IL-17 and tumour necrosis factor play pivotal roles in the pathogenesis of PsA and are targets for its treatment. Biological disease-modifying antirheumatic drugs targeting these cytokines and targeted synthetic disease-modifying antirheumatic drugs targeting Janus kinases are available and widely used in clinical practice. Despite the availability of these drugs, there are still unmet needs; for example, patients often resist treatment and relapse or develop intolerance. Bimekizumab is a humanized monoclonal IgG1 antibody that selectively and directly inhibits IL-17A and IL-17F expression. Recently, the efficacy and tolerability of bimekizumab have been reported in several large clinical trials, including two phase III studies. Bimekizumab brings rapid symptom relief and is effective in patients who are biologic-naïve and those who have inadequate responses or become intolerable to tumour necrosis factor inhibitors and require discontinuation; therefore, it is expected to be a novel blockbuster to overcome the unmet needs of PsA.

Association between baseline cardiovascular risk and incidence rates of major adverse cardiovascular events and malignancies in patients with psoriatic arthritis and psoriasis receiving tofacitinib.

Tofacitinib is a Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA) and has been investigated for psoriasis (PsO). This post hoc analysis examined baseline cardiovascular (CV) disease risk and its association with the occurrence of major adverse cardiovascular events (MACE) and malignancies in tofacitinib-treated patients with PsA and PsO. Included three phase III/long-term extension (LTE) PsA trials and seven phase II/phase III/LTE PsO trials of patients receiving ⩾ 1 dose of tofacitinib. Incidence rates (IRs: patients with events/100 patient-years) for MACE and malignancies (excluding non-melanoma skin cancer) were determined in subgroups according to history of atherosclerotic CV disease (ASCVD), baseline 10-year risk of ASCVD (in patients without history of ASCVD), and baseline metabolic syndrome (MetS). For patients with PsA (N = 783) and PsO (N = 3663), respectively, tofacitinib exposure was 2038 and 8950 patient-years (median duration: 3.0 and 2.4 years), and 40.9% and 32.7% had MetS. Excluding missing CV risk profile data, 51/773 (6.6%) and 144/3629 (4.0%) patients had history of ASCVD, and in patients without history of ASCVD, around 20.0% had intermediate/high baseline 10-year ASCVD risk. For PsA and PsO, IRs of MACE were greatest in those with history of ASCVD or high baseline 10-year ASCVD risk. For PsA, five of six patients with MACE had baseline MetS. Malignancy IRs in patients with PsA were greatest in those with intermediate/high baseline 10-year ASCVD risk. Of these, eight of nine patients with malignancies had baseline MetS. In the PsO cohort, IR of malignancies was notably greater with high versus low/borderline/intermediate baseline 10-year ASCVD risk. In tofacitinib-treated patients with PsA/PsO, increased ASCVD risk and baseline MetS were associated with higher IRs for MACE and malignancies. Our results support assessing CV risk in patients with PsA/PsO and suggest enhanced cancer monitoring in those with increased ASCVD risk. NCT01877668/NCT01882439/NCT01976364/NCT00678210/NCT01710046/NCT01241591/NCT01186744/NCT01276639/NCT01309737/NCT01163253. People who have psoriatic arthritis or psoriasis may have more heart-related problems and cancer if they have a higher risk of cardiovascular disease: A study in people with psoriatic arthritis or psoriasis receiving tofacitinib Why was this study done? • People with psoriatic arthritis (PsA) and psoriasis (PsO) are more likely than the general population to have a disease affecting the heart and blood vessels [cardiovascular (CV) disease].• People who are more likely to have CV disease may also be more likely to have certain types of cancer.• Tofacitinib is a medicine to treat people with PsA and has been tested in people with PsO.• We wanted to know if the risk of CV disease affects the number of heart-related problems (including heart attack, stroke, or death) and cancer in people with PsA and PsO. What did the researchers do? • We used results from 10 clinical trials.• In these trials, people with PsA and PsO were taking tofacitinib 5 or 10 mg twice a day.• After the trials had ended, we measured people's risk of CV disease using a risk calculator. This risk calculator showed if they had a low, borderline, intermediate, or high risk of CV disease over the next 10 years. We also checked if they had had CV disease before treatment.• We checked if people had a group of conditions linked to CV disease: diabetes, high blood pressure, and obesity.• We counted the cases of heart-related problems and cancer in people once they started taking tofacitinib. What did the researchers find? In people with PsA and PsO taking tofacitinib:• There were more cases of heart-related problems and cancer in people who had intermediate or high risk of CV disease.• There were more cases of heart-related problems in people who had had CV disease before.• More people with diabetes, high blood pressure, and obesity had heart-related problems and cancer than people without those conditions. What do the findings mean? • It is important to measure risk and assess history of CV disease in people with PsA and PsO, including those taking tofacitinib.• We should test for cancer in people with high risk of CV disease.

TREATMENT IN PSORIATIC ARTHRITIS: CHOICE AND DETERMINANTS OF RESPONSE

Psoriatic arthritis (PsA) is the second most common inflammatory arthropathy after rheumatoid arthritis in early arthritis clinics. PsA presents as a symmetrical polyarthritis, like rheumatoid arthritis or an asymmetrical oligo-arthritis, with a predilection for the distal interphalangeal joints. Spinal involvement is like ankylosing spondylitis. Joint damage occurs early in up to 50% of PsA patients and has an 11% annual erosion rate in the first 2 years of the disease. There have been significant advances in understanding of PsA pathogenesis in recent years in the areas of genetics and molecular biology implicating both innate and adaptive immune systems. This has led to the introduction of evidence-based targeted therapy, primarily with tumour necrosis factor inhibitor (TNFi) agents. Therapy with disease-modifying anti-rheumatic drugs, such as methotrexate and leflunomide, remains the first-choice therapeutic intervention, even though there are few randomized controlled trials with these agents. In contrast, several successful studies of TNFi agents demonstrate excellent efficacy, in combination with methotrexate, and several novel agents are currently in development for the treatment of PsA. Before the introduction of targeted biologic medications, such as TNF inhibitors, the capacity to control disease activity was limited, with only modest effects noted in most patients with traditional oral medications such as methotrexate and sulfasalazine. Pak J Physiol 2022;18(4):31–4

PsABIOnd Study and eDaily Substudy Design: Long-Term Effectiveness and Safety of Guselkumab and IL-17 Inhibitors in Routine Clinical Practice in Patients with Psoriatic Arthritis.

Randomised clinical studies in psoriatic arthritis (PsA) do not always reflect patients in routine clinical practice. Large-scale data from routine practice are needed to better understand drug persistence, effectiveness and long-term safety of therapeutic agents. PsABIOnd is an international, prospective, observational study designed to collect long-term routine care data in patients with PsA who receive guselkumab (an interleukin-23 [IL-23] inhibitor) or an interleukin-17 (IL-17) inhibitor. Adult patients (≥ 18years) with a confirmed diagnosis of PsA who are starting guselkumab or any approved IL-17 inhibitor as a first, second, third or fourth line of PsA treatment and who provide written informed consent will be eligible to participate. Participants will be followed for a maximum of 36months (+3months) from the start of treatment. Study visits will occur in line with the standard of care, approximately every 6months, plus an additional visit at 3months after the start of treatment. eDaily by PsABIOnd- aneHealth substudy, will document the impact of these treatments on wellbeing and symptoms in a subgroup of participants over a 24-week (+4weeks) observation period on treatment. The primary objective of PsABIOnd is to evaluate treatment persistence with guselkumab and IL-17 inhibitors. Data sources will include validated electronic patient-reported outcomes (ePROs) and physician-completed assessments. Safety data will be collected through reporting adverse events. The eDaily by PsABIOnd substudy will use wearable and digital technologies for continuous activity and sleep monitoring, and frequent patient eDiary and ePRO collection to provide a more detailed and comprehensive picture of PsA. ClinicalTrials.gov identifier: NCT05049798.

The Clinical Significance of Simultaneous IL-17A and IL-17F Blockade in Psoriasis Non-Responding to Anti-IL17A Therapy

The better understanding of the immunopathogenesis of psoriasis has led to the development of highly efficacious targeted therapies with favorable safety profiles. Among them, the class of Interleukin (IL)-17 antibodies are well established for the treatment of psoriasis, psoriatic arthritis and axial spondyloarthritis. Bimekizumab is a new antibody that simultaneously neutralizes IL-17A and IL-17F. We present two patients with psoriasis, who lost response to several biologics, among them IL-17 antagonists such as secukinumab, ixekizumab or brodalumab. Besides plaque-type psoriasis, patients also had psoriasis in hard-to-treat areas such as scalp and groins or psoriatic arthritis. Remarkably, both patients already responded to the therapy with bimekizumab 4 weeks after the first injection and, one year thereafter, both patients sustained PASI100. No side effects were observed. The fast response to bimekizumab emphasizes the crucial role of IL-17F in the pathogenesis of psoriasis. Besides, due to the new mechanism of action, non-responders to other anti-IL-17 therapies could benefit when switched to bimekizumab.

Guselkumab (Tremfya)


 CADTH recommends that Tremfya be reimbursed by public drug plans for the treatment of active psoriatic arthritis (PsA) if certain conditions are met.
 Tremfya should only be reimbursed to treat adult patients with active PsA according to the reimbursement criteria used for other biologic disease-modifying antirheumatic drugs (DMARDs) that are currently reimbursed by public drug plans.
 Tremfya should only be reimbursed if it is prescribed by a rheumatologist or a clinician who has experience treating adult patients with active PsA and if it does not cost more than other biologic DMARDs or targeted synthetic DMARDs. Tremfya should not be reimbursed when used together with other biologic or targeted synthetic DMARDs for active PsA.

Multidisciplinary Rheuma-Derma Clinics: 5 Years of Experience at the San Marco Hospital in Catania.

Early psoriatic arthritis (PsA) diagnosis is critical to prescribe timely treatment to prevent the irreversible joint damage and the many other problems that patients with PsA experience. This retrospective study aimed to highlight the benefits of a Rheuma-Derma Clinic focused on the early diagnosis and prompt treatment of PsA with a shared approach among Italian psoriasis patients. Diagnosing PsA early is the main goal to reduce joint damage and disability in the patients affected. Studies describing the results of rheuma-derma clinics aimed to reach this goal emerged in the last decade. This study presents limitations and advantages typical of retrospective designs. A Rheuma-Derma Clinic was created in 2017 at the Rheumatology Department of the Hospital Policlinico Gaspare Rodolico of the University of Catania in San Marco, Italy. This study compared the number of patients under disease-modifying antirheumatic treatment 5years before and after the joint clinic was created. A rheumatologist and dermatologist simultaneously assessed patients with psoriasis and/or PsA to obtain a rapid multidisciplinary diagnostic approach and a shared therapeutic strategy. In addition, demographic, clinical, and clinimetrics data were collected. The number of patients with PsA receiving biological disease-modifying antirheumatic drugs increased 47% (from 255 to 374 patients) before and after the joint clinic was implemented. Likewise, those receiving conventional synthetic disease-modifying antirheumatic drugs increased by 47% (from 367 to 539) as well. Additionally, for all the clinimetrics evaluated (DAS28, HAQ, BASDAI, DAPSA, PASI, PGA), there was an improvement over the 12months under the Rheuma-Derma Clinic care. The measures that improved the most were DAPSA, PGA, PASI, and BASDAI. The implementation of the Rheuma-Derma Clinic was associated with an increase in the number of patients diagnosed, the number of patients with PsA receiving DMARD treatments, and improvements in clinimetrics among the study participants.

Deucravacitinib: First Approval.

Deucravacitinib (SOTYKTU™) is a first-in-class, highly selective, oral tyrosine kinase 2 (TYK2) inhibitor. It acts via an allosteric mechanism, binding to the catalytically inactive pseudokinase regulatory domain of TYK2 and stabilizing an inhibitory interaction between the regulatory and catalytic domains. Deucravacitinib is being developed by Bristol Myers Squibb for the treatment of multiple immune-mediated diseases, including psoriasis, psoriatic arthritis, lupus and inflammatory bowel disease. It received its first approval (in the USA on 9September 2022) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. On 26 September 2022, it was subsequently approved in Japan for the treatment of plaque psoriasis, generalized pustular psoriasis and erythrodermic psoriasis. The Marketing Authorisation Application for deucravacitinib for the treatment of adults with moderate to severe plaque psoriasis has been validated in the EU, and clinical development of the drug for the treatment of multiple immune-mediated diseases is underway in numerous countries worldwide. This article summarizes the milestones in the development of deucravacitinib leading to this first approval for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

The Role of Interleukin-17 in Juvenile Idiopathic Arthritis: From Pathogenesis to Treatment.

Background and Objectives: Interleukin-17 (IL-17) is a cytokine family consisting of six members and five specific receptors. IL-17A was the first member to be identified in 1993. Since then, several studies have elucidated that IL-17 has predominantly pro-inflammatory activity and that its production is involved in both the defense against pathogens and the genesis of autoimmune processes. Materials and Methods: In this review, we provide an overview of the role of interleukin-17 in the pathogenesis of juvenile idiopathic arthritis (JIA) and its relationship with IL-23, the so-called IL-23-IL-17 axis, by reporting updated findings from the scientific literature. Results: Strong evidence supports the role of interleukin-17A in the pathogenesis of JIA after the deregulated production of this interleukin by both T helper 17 (Th17) cells and cells of innate immunity. The blocking of IL-17A was found to improve the course of JIA, leading to the approval of the use of the human anti-IL17A monoclonal antibody secukinumab in the treatment of the JIA subtypes juvenile psoriatic arthritis (JPsA) and enthesitis-related arthritis (ERA). Conclusions: IL-17A plays a central role in the pathogenesis of JIA. Blocking its production with specific biologic drugs enables the effective treatment of this disabling childhood rheumatic disease.

Pharmacoeconomic aspects of the targeted drugs use in psoriatic arthritis in context of the Russian healthcare system

Objective: to study the clinical and economic aspects of the use of biological disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), Janus kinase inhibitors (JAKi), for the treatment of psoriatic arthritis (PsA).Patients and methods. The study included adult patients (age ≥18) with active PsA, bionaive or previously treated with bDMARDs. Comparison technologies included: adalimumab (ADA), guselcumab, golimumab, ixekizumab, secukinumab (SEC), tofacitinib (TOFA), certolizumab pegol (CZP), upadacitinib (UPA), ustekinumab, etanercept. The efficacy and safety of the bDMARDs and tsDMARDs included in the study were evaluated based on the results of a systematic search and analysis of data on the comparative clinical efficacy and safety of their use. First of all, the results of phase III randomized controlled trials of drugs that are used to treat active PsA in adult patients as active treatment compared with placebo or with another active drug, or systematic reviews with meta-analysis (MA) and network MA based on them, were considered. The period from the 12th to the 24th week after the start of therapy was taken as the time point for assessing the clinical efficacy of drugs, and the frequency of achieving the ACR20/50/70 criteria was taken as the performance indicator. Cost per responder (СpR), calculated on the basis of the cost of PsA therapy by the time a response is achieved according to the ACR20/50/70 criteria, was used as a criterion for clinical and economic efficiency and to analyze the impact on the budget.Results and discussion. The data of the performed MA indicate a significantly greater effectiveness of the analyzed bDMARDs and JAKi compared to placebo in terms of the frequency of achieving a response according to the ACR20/50/70 criteria both in the group of bionaive patients and in the group of PsA patients, previously treated with bDMARDs. There were no differences between the drugs included in the study in terms of the frequency of achieving ACR20/50/70 response during the treatment of PsA. According to the study, by the 24th week of therapy, ADA, UPA and SEC 150 mg were characterized by the lowest costs to achieve the ACR20/50/70 criteria in bionaive patients and ACR20/50 in patients who were previously treated with bDMARDs. A low CpR value was determined in cases of ADA 40 mg and UPA 15 mg use for the treatment of patients with PsA who had not previously received bDMARDs. Among interleukin inhibitors, the lowest CpR value was registered for SEC 150 mg. By the 12th week of treatment, the CpR of TOFA 5 mg was higher compared to that of UPA 15 mg. CpR indicators for achieving ACR20/50 criteria in patients who were previously treated with bDMARDs were lower in UPA 15 mg and CZP compared to other drugs.Conclusion. The results of the study demonstrate the clinical and economic feasibility of introducing different bDMARDs and JAKi into real practice of PsA treatment. At the same time, the use of original drugs is not always associated with significant costs per 1 patient who responded to treatment. In the absence of direct comparisons, real clinical practice provides important information about the relative efficacy and safety of alternative therapies in the management of PsA patients.