Treatment Of Psoriatic Arthritis Research Articles

Cost-effectiveness analysis of bimekizumab for the treatment of active psoriatic arthritis in Sweden

AimsTo evaluate the cost-effectiveness of bimekizumab, an inhibitor of IL-17F and IL-17A, against biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARD) for psoriatic arthritis (PsA) from the Swedish healthcare system perspective.Materials and methodsA Markov model was developed to simulate the clinical pathway of biologic [b] DMARD-naïve or tumor necrosis factor inhibitor experienced [TNFi-exp] PsA patients over a lifetime horizon. Treatment response was incorporated as achievement of the American College of Rheumatology 50% (ACR50) and Psoriasis Area and Severity Index 75% (PASI75) response, and changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score. The efficacy of bimekizumab was obtained from the BE OPTIMAL (bDMARD-naïve) and BE COMPLETE (TNFi-experienced) trials while a network meta-analysis (NMA) informed the efficacy of the comparators. Resource use and drug costs were obtained from published studies and databases of drug retail prices in Sweden. A willingness-to-pay threshold of €50,000 per quality-adjusted life year (QALY) was applied.ResultsIn bDMARD-naïve patients, bimekizumab achieved greater QALYs (14.08) than with all comparators except infliximab (14.22), dominated guselkumab every 4 and 8 weeks, ixekizumab, secukinumab 300 mg, ustekinumab 45 mg and 90 mg, and was cost-effective against risankizumab, tofacitinib, upadacitinib and TNFis, except adalimumab biosimilar. In TNFi-experienced patients, bimekizumab led to greater QALYs (13.56) than all comparators except certolizumab pegol (13.84), and dominated ixekizumab and secukinumab 300 mg while being cost-effective against all other IL-17A-, IL-23- and JAK inhibitors.LimitationsAn NMA informed the comparative effectiveness estimates. Given gaps in evidence of disease management and indirect costs specific to HAQ-DI scores, and sequential clinical trial evidence in PsA, non-PsA cost data from similar joint conditions were used, and one line of active treatment followed by best supportive care was assumed.ConclusionsBimekizumab was cost-effective against most available treatments for PsA in Sweden, irrespective of prior TNFi exposure

Nail psoriasis dynamics during biologic treatment and withdrawal in patients with psoriasis who may be at high risk of developing psoriatic arthritis: a post hoc analysis of the VOYAGE 2 randomized trial

BackgroundNail psoriasis is a common, physiologically, and psychologically disruptive, and yet often under-treated manifestation of psoriasis. The objectives of this analysis were to investigate the trajectory of nail psoriasis, a risk factor for psoriatic arthritis (PsA), with guselkumab vs adalimumab treatment followed by withdrawal, and determine characteristics associated with nail response in patients treated with guselkumab.MethodsThis post hoc analysis of the phase III trial VOYAGE 2 included patients with moderate-to-severe plaque psoriasis and baseline nail involvement. Nail Psoriasis Severity Index (NAPSI) and Psoriasis Area and Severity Index (PASI) were analyzed through week 48 in patients randomized to guselkumab or adalimumab. Multiple logistic regression analyzed factors associated with NAPSI 0/1 at week 24/week 48 following guselkumab treatment. In a separate analysis, patients were stratified by prior biologic experience.ResultsOverall, 272 vs 132 patients receiving guselkumab vs adalimumab had nail psoriasis at baseline. Lower baseline NAPSI and week 16 PASI were associated with achieving NAPSI 0/1 at week 24 (NAPSI, odds ratio 0.685 [95% confidence interval: 0.586, 0.802]; week 16 PASI, 0.469 [0.281, 0.782]) and week 48 (NAPSI, 0.784 [0.674, 0.914]; week 16 PASI, 0.557 [0.331, 0.937]) with guselkumab. Previous biologic experience did not impact NAPSI response. Following treatment withdrawal at week 28, mean NAPSI was maintained in the guselkumab arm (week 24 1.7, week 48 1.9) and increased slightly in the adalimumab arm (week 24 1.4, week 48 2.3). Mean PASI increased across both treatment arms.ConclusionsHigher skin efficacy at week 16 was associated with better nail responses during guselkumab treatment. Nail psoriasis improvements reflected skin improvements. Following guselkumab withdrawal, nail response was maintained longer than skin response. Future studies should investigate whether such improvements in nail response reduce patients’ risk of later PsA development.Trial registrationClinicalTrials.gov, NCT02207244. Registered July 31, 2014.

Treatment with Upadacitinib in Active Psoriatic Arthritis: Efficacy and Safety Data of the First 192 Patients from the UPJOINT Study, a Multicentre, Observational Study in Clinical Practice.

Our aim was to investigate the efficacy and safety of upadacitinib (UPA) in patients with either oligo- or polyarticular active psoriatic arthritis (PsA) using routine clinical practice data from an observational, prospective, multicentre study. This interim analysis contains upadacitinib efficacy and safety data from the UPJOINT study, collected from baseline to the week24 visit with a focus on composite measures, clinical assessments and patient-reported outcomes, amongst others, including minimal disease activity (MDA), very low disease activity (VLDA), Disease Activity Index for Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI), resolution of dactylitis and nail psoriasis and body surface area affected by skin psoriasis (BSA). A total of 296 patients with baseline data and 192 with completed week24 visits were included in the analysis. The proportion of patients achieving MDA increased from 2.7% at baseline to 39.1% at week24 (95%CI 32.1, 46.3). Similarly, the number of patients in DAPSA remission (DAPSA ≤ 4) increased from 0 at baseline to 32 (16.7%) by week24. At that time, 59.4% of the patients were either in DAPSA remission or had low disease activity (DAPSA ≤ 14). During the 24weeks time frame, the proportion of patients with BSA ≤ 3 increased from 80.7% to 91.1%. Furthermore, at weeks12 and 24, 45.14% and 47.19% of affected patients showed a resolution of enthesitis. Active dactylitis and nail psoriasis at baseline were reported to affect 10.5% and 22.0%, decreasing to 2.6% and 5.7% at week24, respectively. The safety findings are consistent with the known safety profile of upadacitinib in rheumatoid arthritis and PsA; no new safety risks were identified. The data from this study confirm the findings of previous randomized controlled trials suggesting UPA is an effective treatment for active PsA without any new safety signals in patients from daily clinical practice. ClinicalTrials.gov identifier, NCT04758117.

The Effects of Biologics on Hematologic Malignancy Development in Patients with Ankylosing Spondylitis, Psoriasis, or Psoriatic Arthritis: A National Cohort Study.

Biologics are used for ankylosing spondylitis (AS), psoriasis, and psoriatic arthritis (PsA) treatment. The association between biologics and the development of hematologic malignancies is controversial, and data on patients with AS, psoriasis, and PsA are scarce. This retrospective cohort study used data from 2010 to 2020 from Taiwan's National Health Insurance Research Database (NHIRD). Patients with AS, psoriasis, and PsA were divided into a biologics and non biologics group after 1:10 propensity score matching. The hematologic malignancy incidences and the time-/dose-dependent effects on biologics were analyzed by Poisson regression to evaluate the incidence rate ratio (IRR). Of the 4157 biologics users and 38,399 non biologics users included in the study, 10 and 72 persons developed hematologic malignancies, respectively. Biologics only significantly increased the risk of hematologic malignancies in non-Hodgkin's lymphoma (IRR: 2.48, 95% confidence interval (CI): 1.28-4.80). Different treatment patterns, types of biologics prescribed, cumulative defined daily doses, comorbidities, and comedications did not significantly affect hematologic malignancy development. A significantly increased risk was observed when biologics had been prescribed for 1-2 years (IRR: 2.95, 95% CI: 1.14-7.67). Clinical professionals should be aware of a patients' risk of hematologic malignancies during the second year of biologic treatment.

Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis

IntroductionPsoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF)...

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.

Efficacy of tofacitinib on enthesitis in patients with active psoriatic arthritis: analysis of pooled data from two phase 3 studies

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post hoc analysis assessed tofacitinib efficacy on enthesitis by baseline location and severity, and impact on disease activity and patient-reported outcomes (PROs), in patients with PsA.MethodsData were pooled from two phase 3 studies (NCT01877668/NCT01882439) in patients with PsA receiving tofacitinib 5 or 10 mg twice daily to month (M)6 or placebo to M3. Endpoints were: change from baseline in Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC); proportions of patients with enthesitis, relapsed enthesitis after resolution, de novo enthesitis, low disease activity (LDA) or remission (minimal disease activity/very low disease activity; Psoriatic Arthritis Disease Activity Score; Disease Activity Index for Psoriatic Arthritis, and Composite Psoriatic Disease Activity in Psoriatic Arthritis); and PROs (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] total and arthritis pain Visual Analog Scale scores). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs was evaluated by multivariate linear regression.ResultsSeven hundred ten patients from two studies were included: 479 had LEI > 0; 545 had SPARCC > 0; and 136 had LEI = 0 and SPARCC = 0 at baseline. At baseline, among patients with LEI > 0 or SPARCC > 0, mean LEI and SPARCC across treatments and enthesitis locations/severities ranged from 1.0–4.4 and 1.3–9.4, respectively. Across several baseline enthesitis locations/severities, changes from baseline in LEI and SPARCC up to M3 were greater with tofacitinib (-2.0–0.4 and -3.5–0.2) vs placebo (-‍0.9–‍0.4 and -1.5–1.1). Enthesitis at M6 was more common in patients with greater baseline enthesitis severity. At M6, ≤ 40% of patients with baseline LEI > 0 or SPARCC > 0 whose enthesitis had resolved by M1/M3 experienced a relapse, and < 14% of patients with baseline LEI = 0 and SPARCC = 0 had de novo enthesitis. LDA/remission rates generally increased with tofacitinib over time. Baseline LEI location was significantly associated with change from baseline in arthritis pain score, while baseline SPARCC severity was significantly associated with change from baseline in FACIT-F total and arthritis pain scores.ConclusionTofacitinib treatment resulted in improvements in enthesitis in patients with PsA, regardless of baseline location or severity.Trial registrationNCT01877668;NCT01882439.

Thyroid abnormality in patients with psoriasis: prevalence and association with severity

BackgroundPsoriasis is associated with several comorbidities and its association with thyroid abnormality has been hypothesized. ObjectiveTo assess the prevalence of thyroid abnormality in Brazilian patients with psoriasis and to analyze its association with severity, presence of psoriatic arthritis and immunobiological treatment. Additionally, to compare results with literature as a control. MethodsIn this observational study, clinical and laboratory data of patients followed from January 2018 to December 2019 were analyzed. Thyroid abnormality was assessed through the current history of thyroid disease and laboratory tests - thyrotropin (TSH), free thyroxine (FT4), antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG) antibodies. Patients were classified according to psoriasis severity - Psoriasis Area and Severity Index (PASI), presence of psoriatic arthritis, and current treatment. Subsequently, the results were compared with a control group selected from the literature review. ResultsOf the 250 included patients, 161 were eligible. The prevalence of thyroid abnormality was 28.57% and of hypothyroidism, 14.91%. The mean age was 55 years and the median PASI was 2.2. There was no association between thyroid abnormality and PASI (p=0.8), presence of psoriatic arthritis (p=0.87), or use of immunobiological therapy (p=0.13). The literature control group included 6,227 patients and there was a statistically significant difference for the hypothyroidism variable (p<0.0001). Study limitationsAbsence of a control group from the same center. ConclusionThis was one of the first Brazilian studies on the prevalence of thyroid abnormality in patients with psoriasis.

Real-world apremilast use in biologic-naïve psoriatic arthritis patients. Data from Spanish clinical practice

IntroductionApremilast is approved for treatment of psoriasis and psoriatic arthritis (PsA). Real-world evidence on apremilast effectiveness in clinical practice is limited. MethodsObservational study enrolling adult patients, across 21 Spanish centres, who had initiated apremilast in the prior 6 (±1) months and were biologic naive. Data were collected at routine follow-up visits 6 and 12 months after apremilast initiation. Primary outcome was 6 and 12-month persistence to apremilast. Secondary outcomes included Disease Activity for PsA (DAPSA), joint erosions, enthesitis, dactylitis, and patient-reported quality of life (QoL, measured using the PsA impact of disease [PsAID] questionnaire). ResultsWe included 59 patients. Most had oligoarticular PsA, moderate disease activity, and high comorbidity burden. Three-quarters were continuing apremilast at 6 months and two-thirds at 12 months; mean (SD) apremilast treatment duration was 9.43 (1.75) months. DAPSA scores showed improved disease activity: one-third of patients in remission or low activity at apremilast initiation versus 62% and 78% at 6 and 12 months, respectively. Eleven of 46 patients with radiographic assessments had joint erosions at apremilast initiation and none at month 12. Median (Q1, Q3) number of swollen joints was 4.0 (2.0, 6.0) at apremilast initiation versus 0.0 (0.0, 2.0) at 12 months. Incidence of dactylitis and enthesitis decreased between apremilast initiation (35.6% and 28.8%, respectively) and month 12 (11.6% and 2.4%, respectively). Over two-thirds of patients had a PSAID-9 score <4 (cut-off for patient-acceptable symptom state) at month 12. ConclusionsIn Spanish clinical practice, two-thirds of PsA patients continued apremilast at 12 months, with clinical benefits at the joint level, no radiographic progression of erosions, and a positive impact on patient-reported QoL.Trial registration number Clinicaltrials.gov: NCT03828045.

The Psoriatic Arthritis Experience in Saudi Arabia from the Rheumatolo-gist and Patient Perspectives.

Psoriatic arthritis (PsA) is a musculoskeletal disease that adversely affects physical mobility and quality of life. It is challenging to manage because of the heterogeneous na-ture of the symptoms and the current treatment options. To explore the patient and rheumatologist perspectives of PsA to help improve understanding of the disease experience and improve disease management. A descriptive, observational cross-sectional study of Saudi Arabian dermatologists and rheumatologists and patients with psoriasis or PsA was conducted. Questionnaire data were collect-ed from 31 dermatologists, 34 rheumatologists, 90 patients with psoriasis, and 98 patients with PsA and analysed using descriptive statistics. Here, data from rheumatologists and patients with PsA are presented. The results revealed similarities and differences in the rheumatologist and patient perspec-tives of PsA. Rheumatologists and patients agreed on the impact that PsA had on patients' quality of life and that more education was needed. However, they differed on several aspects of disease man-agement. Rheumatologists estimated the time to diagnosis as four times shorter than what patients experienced. Patients accepted their diagnosis more than rheumatologists perceived them to; rheu-matologists perceived patients to be worried or fearful. Patients perceived joint pain as their most severe symptom, in contrast to rheumatologists, who presumed skin appearance was the most severe symptom. Reported input into PsA treatment goals differed significantly. More than half of the rheumatologists reported equal patient-physician input into goal development as opposed to <10% of patients reporting the same. Almost half of patients reported no input into the development of their treatment goals. The management of PsA could benefit from enhanced screening and re-evaluation of what PsA outcomes have the most value to patients and rheumatologists. A multidisciplinary ap-proach is recommended with increased patient involvement in disease management and individual-ized treatment options.

Neuropathic Pain in Patients with Psoriatic Arthritis: A Bystander or a Gamechanger?

Objectives&#x0D; &#x0D; The relationship between clinical and laboratory parameters associated with the neuropathic pain presence in Psoriatic Arthritis is not well known and has not been adequately studied. Based on these assumptions, the aim of our study is to investigate how often neuropathic pain occurs in Psoriatic Arthritis patients and how much it is related to the clinical and laboratory parameters of the disease.&#x0D; &#x0D; Methods&#x0D; &#x0D; In the cross-sectional study, 45 Psoriatic Arthritis patients diagnosed according to The Classification Criteria for Psoriatics were included. In our study, Pain Detect Questionnaire (PDQ) was used to assess the neuropathic pain characteristics. Presence of enthesitis was determined by SPARCC to ensure objective measurements. Functional status was evaluated with the Health Assessment Questionnaire (HAQ). The Short Form-36 (SF-36) questionnaire was used to evaluate the quality of life.&#x0D; &#x0D; Results&#x0D; &#x0D; A total of 45 patients were included in the study. The mean duration of symptoms was 78.91 ± 95.8 months. There are 16 patients receiving Nsaid treatment, 28 patients receiving DMARD treatment, and 13 patients receiving biological therapy. Among the patients included in the study, 30 patients with neuropathic pain and 15 without neuropathic pain were found according to the Pain Detect questionnaire. A significant difference was observed between these two groups in the results of DAPSA, VAS movement, HAQ, morning stiffness, and SF-36 Body pain.&#x0D; &#x0D; Conclusion&#x0D; &#x0D; Our study has shown that neuropathic pain has a high prevalence in Psoriatic Arthritis patients. This association was observed to be related to functional limitation. Additionally, the DAPSA score was found to be significantly higher in patients with neuropathic pain due to pain sensation which suggests that it may be a factor reducing treatment success. It is conceivable that the recognition and treatment of neuropathic pain may increase the success of Psoriatic Arthritis treatment.

Persistence and Use of Ixekizumab in Patients with Psoriatic Arthritis in Real-World Practice in Spain. The PRO-STIP Study.

Ixekizumab (IXE) is an IgG4-type monoclonal antibody targeting IL-17A indicated alone or in combination with methotrexate, for the treatment of active psoriatic arthritis (PsA) in adult patients with insufficient response or with intolerance to one or more disease-modifying anti-rheumatic drug (DMARD) therapy. The PRO-STIP study aimed to describe persistence, patient characteristics, treatment patterns, and effectiveness in patients with PsA receiving IXE in a real-world clinical setting in Spain. This was an observational, multicentric, retrospective, longitudinal study in adult PsA patients who started IXE between January 2019 and December 2020, with at least 24weeks of follow-up. A descriptive analysis of patient characteristics and treatment patterns was performed. The primary objective, treatment persistence, was estimated by Kaplan-Meier survival curve. Effectiveness was evaluated by Disease Activity in Psoriatic Arthritis (DAPSA) scores at baseline and at 12 and 24weeks. Eighty-nine patients met the selection criteria (55.1% women and mean age 51.5years). The median time from PsA diagnosis to starting IXE was 7.7years (IQR 3.4-14.6). Prior to IXE, 95.5% patients had been treated with at least one biologic or targeted synthetic DMARD (b/tsDMARD). The observed persistence rates were 95.5%, 84.3% and 68.5% at 24, 48, and 104weeks, respectively. The median persistence was not reached in the study period (mean persistence, 86.9 [95% CI 80.6-93.2] weeks). Twenty-eight (31.5%) patients discontinued IXE, 19 patients (21.3%) due to loss of effectiveness and two patients (2.2%) due to adverse events. In patients receiving treatment and with available effectiveness assessment (n = 24), DAPSA decreased significantly from baseline 23.7 (95% CI 19.5-27.9) to 14.8 (95% CI 10.5-19.2) at 12weeks (p = 0.005) and 14.3 (95% CI 11.1-17.4) at 24weeks (p = 0.004). PsA patients treated with IXE in a real-world setting show high treatment persistence through 104weeks and improvements in disease activity after treatment initiation. This suggests that IXE could be an effective treatment for patients with PsA. Date of registration: 25th May 2021.

Golimumab for Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis: Pharmacologic and Clinical Considerations.

Psoriatic arthritis is a chronic debilitating autoimmune condition, and when diagnosed in patients before the age of eighteen, it is considered pediatric polyarticular juvenile idiopathic arthritis. Monoarticular or polyarticular psoriatic arthritis can be distinguished from other arthropathies by its unique cutaneous manifestations. With numerous treatments already in clinical practice, there are numerous options for treatment. The current literature indicates an elevated level of tumor necrosis factor is present in the epidermis of patients with psoriatic arthritis when compared with the general population. For this reason, anti-tumor necrosis factor therapies have become a hallmark option for psoriatic arthritis patients. Golimumab, a human monoclonal antibody tumor necrosis factor-alpha (TNF-a) receptor antagonist, was chosen as the focus therapy for this investigation. The mechanism of action behind anti-tumor necrosis factor-alpha blockers involves the binding of human TNF-a soluble and transmembrane proteins to competitively inhibit TNF-a from binding to its cellular receptors. The present investigation evaluated current treatment options available for both juvenile- and adult-onset psoriatic arthritis and compared them with the efficacy seen with golimumab use. Pediatric patients included children ages 2-17, while adult populations included adults 18-83 years old. The Food and Drug Administration has approved golimumab for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and polyarticular juvenile idiopathic arthritis. The results of four different studies reporting on the therapeutic effects and adverse events of golimumab use in psoriatic arthritis, juvenile psoriatic arthritis, juvenile idiopathic arthritis, and juvenile polyarticular arthritis were used for comparison. The meta-analysis referenced studies including children ages 2-17 with no reference mentioning children less than age 2. Based on the results of each study, it can be concluded that golimumab, a human monoclonal antibody that prevents the activation of cellular inflammatory reactions when it binds to the TNF-a receptor, is an effective option for patients with active psoriatic arthritis and psoriatic juvenile idiopathic arthritis and for patients who are no longer responding to their current treatment with adalimumab. Each study also reported minimal adverse events associated with golimumab use, and the drug can be safely used in the pediatric population.

Inflammatory Cytokines in Psoriatic Arthritis: Understanding Pathogenesis and Implications for Treatment.

Psoriatic arthritis (PsA) is a persistent, inflammatory disease that affects individuals with psoriasis, arthritis, and enthesitis. Research has demonstrated that inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23), and interleukin-17 (IL-17) play a pivotal role in both the onset and progression of PsA. These cytokines are generated by activated immune cells and stimulate the attraction of inflammatory cells to the synovium and joint tissues, resulting in the deterioration of cartilage and bone. The blocking of these cytokines has become a successful treatment strategy for PsA, as biological drugs that inhibit TNF-α, IL-23, and IL-17 have demonstrated notable clinical benefits. The association between PsA and other types of inflammatory cytokines or chemokines, excluding TNF-α, IL-23, and IL-17, has been extensively investigated in numerous studies. These findings may provide a chance for the discovery of novel therapeutic agents targeting other molecules, distinct from the currently approved biologics and targeted synthetic disease-modifying anti-rheumatic drugs. In this review, we discuss the current understanding of the role of inflammatory cytokines in PsA pathogenesis and clinical implications of targeting these cytokines for PsA treatment.

Janus kinase inhibitors for the treatment of psoriatic arthritis.

Psoriatic arthritis (PsA), a systemic disease, has multi-domain musculoskeletal pathologies along with dermatological manifestations. The current recommendations and the standard of care for the treatment of PsA is to address the domain-based pathologies and the disease severity of the six clinical domains unique to PsA, namely, arthritis of the large and small joints, skin involvement, nail involvement enthesitis, dactylitis and axial disease. With currently available therapies, there are good numbers of primary/secondary non-responders and there are added concerns because of intolerance and adverse effects. In that respect, JAK/STAT inhibitors bring new options for many such patients with psoriasis and PsA. Here, we will discuss currently approved JAK inhibitors for PsA and the others which are in different phases of development, including the TYK2 inhibitors.

Discovery of a Potent and Selective Tyrosine Kinase 2 Inhibitor: TAK-279.

TYK2 is a key mediator of IL12, IL23, and type I interferon signaling, and these cytokines have been implicated in the pathogenesis of multiple inflammatory and autoimmune diseases such as psoriasis, rheumatoid arthritis, lupus, and inflammatory bowel diseases. Supported by compelling data from human genome-wide association studies and clinical results, TYK2 inhibition through small molecules is an attractive therapeutic strategy to treat these diseases. Herein, we report the discovery of a series of highly selective pseudokinase (Janus homology 2, JH2) domain inhibitors of TYK2 enzymatic activity. A computationally enabled design strategy, including the use of FEP+, was instrumental in identifying a pyrazolo-pyrimidine core. We highlight the utility of computational physics-based predictions used to optimize this series of molecules to identify the development candidate 30, a potent, exquisitely selective cellular TYK2 inhibitor that is currently in Phase 2 clinical trials for the treatment of psoriasis and psoriatic arthritis.

Prologue: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 Annual Meeting.

The 2022 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held from July 14 to 17, 2022, in New York City, New York, USA, and was attended by 420 rheumatologists, dermatologists, basic scientists, allied health professionals, patient research partners, and industry partners from 31 countries. A GRAPPA executive retreat, a Trainee Symposium, and the Patient Research Partners Network meeting were held prior to the annual meeting. Presentations included updates in basic research, focusing on biomarkers, personalization of treatments, and the promise of single-cell omics, elucidating the pathogenesis of psoriatic disease (PsD). Presentations also highlighted guttate and plaque psoriasis (PsO), the impact of coronavirus disease 2019 (COVID-19) and its treatments on patients with PsD globally, and the effects of sex and gender in PsD. Reports of ongoing projects included an update on the recently published treatment recommendations, educational initiatives, and the Diagnostic Ultrasound Enthesitis Tool (DUET) study. A session on early identification of psoriatic arthritis (PsA) among patients with PsO included an update on PsA screening tools. Debates were held on whether early intervention for PsO will reduce PsA, whether interleukin (IL)-17 or IL-23 inhibition is a better treatment for PsO and PsA, similarities and differences between axial PsA and axial spondyloarthritis with PsO, and data affecting the understanding of guttate and plaque PsO. Reports from the International Dermatology Outcome Measures (IDEOM) and Young GRAPPiAns concurrent sessions were presented in addition to reports of several other partner groups. Here, we highlight features of the annual meeting and introduce the manuscripts published together as a meeting report.

Difficult to Treat and Refractory to Treatment in Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a complex and chronic inflammatory condition in which the achievement of the best possible disease control has been proposed as the treatment target, which includes the possibility of reaching remission in all disease domains. However, due to the complexity of this multidomain disease, some patients may still have high disease activity in one or more domain and a high burden of disease, potentially leading to various treatment changes and to difficulty with the overall management. In this paper, we overview the concept of patients with difficult-to-treat PsA and the concept of patients with refractory-to-treatment PsA by providing a distinction between these two concepts and the possible implication for the management of patients withPsA.

Clinical practice guideline for the treatment of psoriatic arthritis in Colombia

IntroductionPsoriatic arthritis is a chronic inflammatory arthropathy characterized by subtypes with distinct phenotypes and variable clinical course, which requires optimal management of joint manifestations and skin involvement. ObjectivesThis study aims to provide recommendations for the pharmacological treatment of psoriatic arthritis based on evidence and applicability to the Colombian health system. Methodology and methodsThese guidelines were developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Clinical experts, rheumatologists, and dermatologists formulated the recommendations based on clinical evidence, the disease's impact, patient values and preferences, and the resource availability in the country. ResultsThe guideline includes 12 recommendations related to the use of anti-inflammatory drugs, glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs), including conventional synthetics, biologics, and targeted synthetic DMARD, for the PsA domains: peripheral disease, axial disease, enthesitis, and dactylitis. ConclusionsThis document presents a set of updated and evidence-based recommendations that guide decision-making about pharmacological management of psoriatic arthritis in adults in Colombia. They constitute general guidelines that should be interpreted and implemented according to the individualized evaluation of the patient and the medical criteria in the different clinical settings.

Evidence-based modalities in the management of Psoriasis and Psoriatic arthritis.

Psoriasis is a waxing and waning skin disorder, often associated with a plethora of co-morbidities, including psoriatic arthritis (PsA), a severe form of chronic inflammatory arthritis. All forms of psoriasis and PsA are immune-mediated diseases where the patient's immune system is overactive in the production of certain factors that stimulate and activate the function of certain immune cells. Recent evidence has uncovered an important role for cell-mediated immunity in the aetiology and course of psoriasis and PsA, with a critical role played by the pro-inflammatory IL-23/TH17 axis. Taken together, these new lines of evidence suggest new and improved therapeutic interventions for patients with psoriasis and PsA. The hypothesis-driven process of inquiry of the best available evidence and its implication, application and evaluation in the context of clinical practice pertains to the meta-science of evidence-based health care (EBHC). EBHC consists in the initial step of research synthesis and generation of the systematic review of the best available evidence, estimated both qualitatively and quantitatively (i.e., meta-analysis). Evidence-based decision-making, a process driven and controlled by the expertise of the clinician and by the clinical needs and personal wants of the patient, is the principal, most timely and critical aspect of evidence-based practice. Recent and systematic reviews for the treatment of psoriasis and PsA consistently updated for emerging new and revised data (i.e., living systematic reviews) confirm the efficacy and the effectiveness of methotrexate (MTX) in containing and controlling psoriasis. The outcomes of MTX intervention for PsA remain mixed and inconclusive.