Treatment strategies for Spondyloarthritis: Implementation of precision medicine - Or "one size fits all" concept?

Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations.

Treatment-emergent Candida infections in patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis treated with ixekizumab: an integrated safety analysis of 25 clinical studies.

BACKGROUND: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). RESEARCH DESIGN AND METHODS: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure. RESULTS: Candida infections had an IR of 1.9 per 100 PY in patients with PsO (N = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA (N = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA (N = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit. CONCLUSIONS: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications. TRIAL REGISTRATION: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material.

Ixekizumab (IXE) is a drug approved for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis. IXE belongs to the class of molecules that blocks a protein called interleukin-17A. Since interleukin-17A is involved in the defense against fungi, the clinical use of this class of drug has the potential to increase the risk of developing fungal infections, such as Candida infections.Therefore, researchers collected safety data from 25 clinical studies comprising 9225 adult patients treated with IXE: 6892 with psoriasis, 1401 with psoriatic arthritis, and 932 with axial spondyloarthritis. Researchers looked at the rate of new cases of Candida infections, the so-called incidence rate, and found that 1.9 per 100 patient-years experienced at least 1 Candida infection in the psoriasis group, 2.0 per 100 patient-years in the psoriatic arthritis group, and 1.2 per 100 patient-years in the axial spondyloarthritis group.Across indications, the majority of Candida infections (i) were experienced only once by patients, (ii) were mild or moderate in severity, (iii) involved infections caused by superficial skin fungus in the mouth or genitals, (iv) were considered recovered/resolved during the studies, (v) did not lead to IXE discontinuation, (vi) were managed with topical anti-fungal medications or no medications, and (vii) were typically resolved before next visit.In conclusion, this safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications.

Deepening the Understanding of Inflammatory Conditions Through Rheumatology Education in Family Medicine: An Autoethnography.

Introduction Rheumatic diseases, such as rheumatoid arthritis (RA) and psoriatic arthritis, significantly affect quality of life and require comprehensive management, especially where rheumatologists are scarce. Family physicians in rural settings play a crucial role in providing this care. This study aims to elucidate the educational process for family physicians in managing RA within rural hospitals. Methods Using a qualitative autoethnographic approach, we explored the learning experiences of family physicians at Unnan City Hospital in rural Japan. Data were collected through semi-structured interviews, direct observation, reflective field notes, and informal conversations with participants. The study focused on the practical education of RA management facilitated by a family physician with expertise in rheumatology. Results Three main themes emerged: (1) comprehending arthritis as a systemic disease, (2) managing dynamic conditions with prudence, and (3) providing comprehensive and continuous care amid uncertainty. Participants initially viewed arthritis as a localized condition but learned to approach it as part of systemic inflammation. They recognized the fluctuating nature of autoimmune diseases, emphasizing the need for cautious and flexible management. Continuous monitoring and a comprehensive approach to patient care with enduring uncertainty were identified as essential for effective RA management. Conclusion The study highlights the importance of experiential learning and mentorship in educating family physicians about RA in rural settings. Understanding arthritis as a systemic condition, exercising prudence in treatment, and maintaining comprehensive care amid uncertainty are crucial components of effective management. These findings inform the development of targeted educational programs for family medicine residents, ultimately enhancing patient care in rural areas. Future research should include multiple rural settings and quantitative data to validate and expand upon these insights.

Real-World Experience With Janus Kinase Inhibitors in Immune-Mediated Diseases: Clinical Experience of a University Hospital.

BACKGROUND: Several Janus kinase (JAK) inhibitors have been developed in recent years. These agents are widely applicable in clinical practice as an alternative treatment for immune-mediated diseases. While the safety and efficacy profile of these drugs has been evaluated in several randomized clinical trials and studies, very few authors have assessed safety and effectiveness under the real-world conditions of daily clinical practice. OBJECTIVE: This study aims to describe the effectiveness and safety of JAK inhibitors in daily clinical practice for the treatment of immune-mediated rheumatic diseases in a university hospital. METHODS: We performed a single-center observational, descriptive, retrospective study of all patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) receiving active treatment with JAK inhibitors between March 2022 and February 2023. We recorded study variables from the clinical history for subsequent analysis using STATA 12.0 (StataCorp LLC, College Station, TX). A 95% confidence interval was applied. RESULTS: The final analysis was performed on 64 patients (upadacitinib: 27, baricitinib: 16, tofacitinib: 13, filgotinib: eight), with a mean age of 55.69±10.78 years (60.94% females). The distribution by disease was as follows: RA, 44 (70.31%); SpA, 11 (17.18%); and PsA, eight (12.5%). A significant improvement was observed in all groups at six to 12 months, as follows: RA, remission in 48.89% and low activity in 26.67%; SpA, remission in 9.09% and low activity in 54.54%; and PsA, low activity in 87.5%. The factors most associated with poor response to treatment were activity before initiation of treatment and previous failure of biological disease-modifying antirheumatic drugs (bDMARDs). Adverse effects and complications were detected in 26.56% (SARS-CoV-2, one case; basal cell carcinoma, one case; and herpes zoster, two cases). There were no reports of cardiovascular or thromboembolic events, opportunistic infection, or tuberculosis. CONCLUSIONS: Our real-world data show that treatment with JAK inhibitors leads to a high rate of remission/low activity that remains unchanged at six to 12 months in RA, SpA, and PsA. The predictors of a poor response to JAK inhibitors in our study population were the level of activity before initiation of treatment and previous failure of bDMARDs. No cardiovascular or thromboembolic events were reported. Of note, we did record one case of severe infection, one case of basal cell carcinoma, and two cases of herpes zoster.

Efficacy and Safety of Tofacitinib in Patients with Psoriatic Arthritis or Ankylosing Spondylitis by Cigarette Smoking Status.

INTRODUCTION: Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening. METHODS: Pooled data from phase 3 and long-term extension (safety only) PsA trials and phase 2 and 3 AS trials were assessed by current/past versus never smoker status. Analysis included efficacy and safety data for tofacitinib 5 (PsA/AS) and 10 (PsA only) mg twice daily (BID) or placebo, and safety data in AS for tofacitinib 2 and 10 mg BID. Efficacy outcomes included American College of Rheumatology ≥ 50% responses (ACR50) and minimal disease activity (MDA) responses to month (M)6/M3 (tofacitinib/placebo) in PsA; and ≥ 40% improvement in Assessment of SpondyloArthritis international Society responses (ASAS40) and AS Disease Activity Score (ASDAS) < 2.1 responses to week (W)16 in AS. Safety was assessed to M48/W48 (PsA/AS), adjusted for treatment/smoking status/median body mass index (BMI) status/sex/trial/treatment-smoking status interaction. RESULTS: PsA/AS cohorts included 342/178 current/past and 572/194 never smokers. Tofacitinib efficacy was generally greater versus placebo to M3/W6 (PsA/AS), and comparable in current/past and never smokers to M6/W16 (PsA/AS). In patients receiving ≥ 1 tofacitinib dose, adjusted treatment-emergent adverse event (TEAE)/serious AE (SAE)/discontinuation due to AE incidence rates (IRs) to M48 in PsA were higher in current/past versus never smokers; adjusted IRs to W48 in AS were higher in current/past versus never smokers for TEAEs, but similar for SAEs/discontinuation due to AEs. CONCLUSIONS: In both patients with PsA and AS, tofacitinib efficacy was greater versus placebo, and comparable across smoking categories. Adjusted IRs were higher in current/past versus never smokers for TEAEs, SAEs, discontinuation due to AEs in PsA, and for TEAEs in AS, complementing reports of associations between smoking and comorbidities in spondyloarthritis. Findings support increased surveillance/caution for patients with PsA or AS with smoking history. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616.

Guselkumab in Biologic-Naïve Patients with Active Psoriatic Arthritis in Russia: A Post Hoc Analysis of the DISCOVER-1 and -2 Randomized Clinical Trials.

INTRODUCTION: There are limited data on the use of advanced therapies to treat psoriatic arthritis (PsA) in Russia. Guselkumab, an interleukin (IL)-23p19-subunit inhibitor, demonstrated efficacy in patients with PsA in the phase 3 DISCOVER-1 and -2, and COSMOS trials. This analysis evaluated the efficacy and safety of guselkumab in patients with PsA in Russia. METHODS: This post hoc analysis of DISCOVER-1 and -2 included 1002 biologic-naïve patients with active PsA from Russia (n = 317) and the rest of the world (RoW; n = 685). Patients received guselkumab 100 mg every 4 weeks (Q4W), or at week 0 and 4 then Q8W, or placebo then guselkumab Q4W at week 24 (Russian: n = 119, 88, and 110, respectively; RoW: n = 216, 246, and 223, respectively). Outcomes through week 52 were pooled (DISCOVER-1 and -2); outcomes from week 52 to 100 represent DISCOVER-2 only. RESULTS: In patients from Russia, ≥ 20% improvement in the American College of Rheumatology (ACR20) criteria response rates were higher with guselkumab vs. placebo at week 24, increased through week 52, and were consistent across all guselkumab-treated groups at week 100. Similar trends were generally observed for ACR50, ≥ 90% improvement in Psoriasis Area and Severity Index (PASI90), achievement of Disease Activity in Psoriatic Arthritis (DAPSA) low disease activity/remission and minimal disease activity, enthesitis and dactylitis resolution, ≥ 0.35 improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) score, improvement in patient-reported pain, and measures in patients with axial PsA (including Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS], and patient-reported spinal pain). Efficacy responses were similar between patients from Russia and the RoW across all endpoints and timepoints. The safety profile of guselkumab in patients from Russia was consistent with previous findings. CONCLUSION: This analysis demonstrated that the safety and efficacy profiles of guselkumab across all PsA domains and patient-reported outcomes in patients from Russia were similar to those in patients from the RoW. TRIAL REGISTRATION NUMBERS: NCT03162796 and NCT03158285.

Cardiovascular comorbidities in psoriatic arthritis: state of the art.

Psoriatic arthritis (PsA) is a complex multi-system immune-mediated condition, characterised by a high comorbidity burden, one of the most prevalent of which is cardiovascular disease (CVD), affecting up to 80% of patients. This narrative review explores the current understanding of cardiovascular comorbidities in PsA, focusing on mechanistic pathways, risk assessment, and the impact of treatment choices on cardiovascular health. Here, we outline the role of inflammatory cytokines, immune system dysregulation, and genetic predispositions in PsA, not only as drivers of musculoskeletal manifestations but also atherosclerosis and endothelial dysfunction, giving rise to cardiovascular pathology. Given these insights, accurately assessing and predicting cardiovascular risk in PsA patients is a critical challenge. This review evaluates traditional risk calculators as well as innovative biomarkers and imaging techniques, emphasising their utility and limitations in capturing the true cardiovascular risk profile of PsA patients. There are multiple complexities surrounding the treatment of PsA in the context of concurrent CVD, and therapeutic choices must carefully balance efficacy in managing PsA symptoms with the potential cardiovascular implications. A multidisciplinary approach, integrating dermatological, rheumatological, and cardiological perspectives, amongst others, to optimise patient outcomes, is key. Overall, a heightened clinical awareness and research focus on cardiovascular comorbidities in PsA is warranted, aiming to refine risk assessment strategies and therapeutic interventions that holistically address the multifaceted needs of patients with PsA.

Sonoanatomy of the Finger Synovio-Entheseal Complexes.

OBJECTIVES: The objectives of this ultrasound and anatomical study were: (1) To evaluate the reliability of ultrasound identification of the enthesis of the central slip of the extensor digitorum tendon (CSET) using cadaver specimens; (2) To assess the concordance of the measurement of the CSET thickness by ultrasound and gross anatomy; (3) To evaluate the variation in ultrasound identification of the CSET enthesis in a cadaveric experimental model of PIP synovitis. METHODS: Four rheumatologist ultrasonographers blindly and independently measured by ultrasound the CSET enthesis thickness in the second to fifth fingers of 8 hands from fresh-frozen human cadavers in two rounds. These fingers were dissected and the thickness of the CSET measured by the anatomist. In addition, an artificial synovitis was created in the proximal interphalangeal (PIP) joints of a different cadaveric hand. The ultrasonographic CSET enthesis thickness was measured by the four investigators before and after intra-articular ultrasound guided injection of material. RESULTS: Intra- and inter-observer reliability of CSET enthesis thickness measurement were good to excellent (ICC 0.93 for intra-observer agreement and 0.89-0.92 for inter-observer agreement). Ultrasound measurements were consistent and only slightly smaller than the anatomical ones (µ = -0.039 mm). The differences between the measurements of CSET enthesis thickness before and after the synovitis model were not statistically significant. CONCLUSION: Ultrasound demonstrated high multiobserver reliability and agreement with gross anatomy in identifying the CSET enthesis and discriminated it from the capsular tissue of the PIP. Furthermore, an experimental model of PIP synovitis did not interfere with its identification.

Successful treatment of the dupilumab-induced psoriatic dermatitis/arthritis and atopic dermatitis with a JAK inhibitor: A case report and literature review.

Dupilumab-induced psoriatic dermatitis and arthritis in a patient with atopic dermatitis were effectively managed with upadacitinib, highlighting the use of Janus kinase inhibitors as a possible treatment for biologic therapy side effects.

Predicting Psoriatic Arthritis in Psoriasis Patients - A Swiss Registry Study.

Background: Psoriatic arthritis (PsA) is a prevalent comorbidity among patients with psoriasis, heavily contributing to their burden of disease, usually diagnosed several years after the diagnosis of psoriasis. Objectives: To investigate the predictability of psoriatic arthritis in patients with psoriasis and to identify important predictors. Methods: Data from the Swiss Dermatology Network on Targeted Therapies (SDNTT) involving patients treated for psoriasis were utilized. A combination of gradient-boosted decision trees and mixed models was used to classify patients based on their diagnosis of PsA or its absence. The variables with the highest predictive power were identified. Time to PsA diagnosis was visualized with the Kaplan-Meier method and the relationship between severity of psoriasis and PsA was explored through quantile regression. Results: A diagnosis of psoriatic arthritis was registered at baseline of 407 (29.5%) treatment series. 516 patients had no registration of PsA, 257 patients had PsA at inclusion, and 91 patients were diagnosed with PsA after inclusion. The model's AUROCs was up to 73.7%, and variables with the highest discriminatory power were age, PASI, physical well-being, and severity of nail psoriasis. Among patients who developed PsA after inclusion, significantly more first treatment series were classified in the PsA-group, compared to those with no PsA registration. PASI was significantly correlated with the median burden/severity of PsA (P = .01). Conclusions: Distinguishing between patients with and without PsA based on clinical characteristics is feasible and even predicting future diagnoses of PsA is possible. Patients at higher risk can be identified using important predictors of PsA.

Subclinical dactylitis represents a more active phenotype of psoriatic arthritis.

OBJECTIVE: Dactylitis has been identified as an important feature of psoriatic arthritis (PsA) with poorer prognosis. Moreover, ultrasound can reveal subclinical dactylitis, however its significance is unclear. Therefore, in this study we aimed to determine the impact of subclinical dactylitis on PsA severity. METHODS: The study was performed based on the PKUPsA cohort. Patients with complete ultrasound assessment on synovitis, tenosynovitis, and soft tissue of both hands and feet were recruited. They were further classified into subgroups based on the presence of clinical or ultrasound evidence of dactylitis. Their clinical characteristics were compared. RESULTS: Among the 223 PsA patients enrolled, there were 90 (40.4%) patients with clinical manifestations of dactylitis (clinical dactylitis group), 26 (11.7%) with evidence of dactylitis on ultrasound however not on physical examination (subclinical dactylitis group), and 107 (47.9%) patients with neither clinical nor ultrasound evidence of dactylitis (no-dactylitis group). Compared with no-dactylitis group, patients in clinical dactylitis group had more swollen joint count (4 vs 2, P<0.01), tender joint count (4 vs 3, P<0.05), and greater median disease activity index in PsA (DAPSA) (25.0 vs 18.3, P<0.05). Moreover, 116 PsA patients in clinical dactylitis or subclinical dactylitis groups also had more tender joint count (4 vs 2, P<0.01), swollen joint count (4 vs 3, p<0.001), median C reactive protein levels (18.1 vs 11.8, P<0.05) and median DAPSA scores (25.5 vs 16.1, P<0.01). Even excluding the digits with dactylitis from counting, the swollen joint count of 116 patients with dactylitis remained significantly greater than that of no-dactylitis group (3 vs 2, P<0.01). 26 patients in subclinical dactylitis group also showed significantly higher DAPSA scores (27.2 vs 16.1, P<0.05), more swollen joint count (4.5 vs 2, P<0.01) and tender joint count (5 vs 3, P<0.05) than no-dactylitis group. CONCLUSION: Subclinical dactylitis also represents a more active phenotype of PsA, which calls for more attention and probably more aggressive therapy.

Monotherapy or combination therapy in PsA: current aspects.

Psoriatic arthritis (PsA) is an immune-mediated inflammatory disease with heterogeneity regarding its clinical features, mainly affecting the skin and the musculoskeletal system; additionally, extra-musculoskeletal manifestations and comorbidities are common, adding complexity to its treatment. In the last decades, a plethora of therapeutic options have been available, including conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), and many recommendations have been published regarding the proper use of them in patients with PsA. In rheumatoid arthritis, the combination of conventional with bDMARDs or tsDMARDs is a common and recommended practice, whereas in PsA there is scarce data about the benefit of this combination. This review summarizes all the available data from randomized clinical trials, observational studies, and registries about the value of this therapeutic strategy.

Use of b/tsDMARDs in PsA: with or without csDMARDs Over the last years, many different b/ts DMARDs have been porven to be efficacious in psoriatic arthritis (PsA). Although in rheumatoid arthritis, it is established that most of these drugs work better in combination with conventional synthetic DMARDs (e.g methotrexate), this seems to be slightly different in PsA. Herein, we review the current literature about the combination therapy versus monotherapy of b/ts DMARDs in PsA. We present the results of this narrative review in a structured (per drug category) way, so that it is easier for the reader to find relevant information. There is no doubt that the currently available treatment options in PsA have changed the course of the disease and improved the functional status of the patients. However, as there is still a substantial proportion of patients who do not achieve remission or low disease activity, the need to find effective therapeutic regimens or follow different strategies is growing. In this direction, the combination of a conventional synthetic with biological or targeted synthetic DMARD does not seem to be more effective than the monotherapy of the latter. This seems to be more pronounced in the newer drug categories (anti-IL-17, anti-IL23 and JAKi) compared to the TNFi, where the co-administration of a csDMARD improves their survival.

Neutrophil exhaustion and impaired functionality in psoriatic arthritis patients.

Background: Neutrophils (polymorphonuclear leukocytes, PMNs) are the most abundant subtype of white blood cells and are among the main actors in the inflammatory response. Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting both the axial and peripheral joints. Typically associated with psoriasis, PsA can also affect multiple systems and organs, including the nails and entheses. Despite the involvement of PMNs in PsA, their specific role in the disease remains poorly understood. This study aimed to characterize the biological functions of PMNs and neutrophil-related mediators in PsA patients. Materials and methods: 31 PsA patients and 22 healthy controls (HCs) were prospectively recruited. PMNs were isolated from peripheral blood and subjected to in vitro stimulation with lipopolysaccharide (LPS), N-Formylmethionyl-leucyl-phenylalanine (fMLP), tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate (PMA), or control medium. Highly purified peripheral blood PMNs (>99%) were evaluated for activation status, reactive oxygen species (ROS) production, phagocytic activity, granular enzyme and neutrophil extracellular traps (NETs) release. Serum levels of matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), TNF, interleukin 23 (IL-23), and interleukin 17 (IL-17) were measured by ELISA. Serum Citrullinated histone H3 (CitH3) was measured as a NET biomarker. Results: Activated PMNs from PsA patients displayed reduced activation, decreased ROS production, and impaired phagocytic activity upon stimulation with TNF, compared to HCs. PMNs from PsA patients also displayed reduced granular enzyme (MPO) and NET release. Serum analyses revealed elevated levels of MMP-9, MPO, TNF, IL-23, IL-17, and CitH3 in PsA patients compared to HCs. Serum CitH3 levels positively correlated with MPO and TNF concentrations, and IL-17 concentrations were positively correlated with IL-23 levels in PsA patients. These findings indicate that PMNs from PsA patients show reduced in vitro activation and function, and an increased presence of neutrophil-derived mediators (MMP-9, MPO, TNF, IL-23, IL-17, and CitH3) in their serum. Conclusions: Taken together, our findings suggest that PMNs from PsA patients exhibit an "exhausted" phenotype, highlighting their plasticity and multifaceted roles in PsA pathophysiology.

Development of a questionnaire to assess the patient perspective regarding challenges in psoriatic arthritis treatment-a mixed-methods study.

BACKGROUND: Limited data exist on psoriatic arthritis (PsA) treatment in lower-income regions, particularly from the patient perspective. This study explores the challenges faced by socioeconomically vulnerable PsA patients and the reasons for non-adherence to treatment guidelines. The main objective of the study is to develop a questionnaire to identify the primary challenges in PsA treatment adherence and to analyze its feasibility while simultaneously understanding the target population's unique characteristics. METHODS: We included PsA patients meeting the Classification Criteria for PsA (CASPAR), excluding those with other overlapping inflammatory diseases. The study, supported by two patient-research partners, began with focus groups to identify treatment challenges, leading to the creation of a 26-item questionnaire. Its reliability was verified using the test-retest method, targeting a percent agreement ≥ 0.8. Then, PsA patients at a rheumatology clinic completed the final survey. RESULTS: The study involved 69 PsA patients. The final questionnaire contained 26-questions across five-domains, with a 92.2% agreement rate and an average completion time of 8.3 minutes. Diagnostic delays exceeded a year for 59% of patients and more than two years for 33%. Daily life disruptions affected 43.2% of patients, with 35.3% taking sick leave or retiring. Around 25% waited over 8 weeks for drug approval, and 17.6% required legal intervention to access medication. Drug dispensation issues impacted about 60% of patients. Furthermore, 66.7% lived far from their rheumatologist, with 49% traveling over an hour for appointments. Approximately 30% were unaware of the risks of methotrexatein relation to alcohol consumption and pregnancy. CONCLUSIONS: The questionnaire was feasible and reliable, with its results underscoring patient-centric challenges in PsA management, particularly concerning diagnostic delays and medication access, as well as daily life disruptions and misinformation. These findings emphasize the urgency for healthcare reforms aimed at improving diagnosis efficiency, patient education, and streamlined medication access, emphasizing the need for tailored initiatives to improve the healthcare experience for PsA patients.

New Ustekinumab Biosimilar Candidate FYB202: Pharmacokinetic Equivalence Demonstrated in a Randomized, Double-Blind, Parallel-Group, Single-Dose Trial in Healthy Subjects.

In the RUSTIC trial, pharmacokinetic (PK) similarity between the proposed ustekinumab biosimilar FYB202 and EU-approved (EU-Ref) and US-licensed ustekinumab (US-Ref) as well as between both reference drugs was assessed after a single 45-mg subcutaneous injection. Safety analyses comprised immunogenicity (antidrug antibodies, neutralizing antibodies), adverse events, and local tolerability. Overall, 491 healthy adults were randomized 1:1:1 and observed for up to 112 days; 486 completed the trial, and 478 were included in the PK analysis. All 3 comparisons showed PK similarity, since the 90% confidence intervals of the respective geometric mean ratios for area under the concentration-time curve from time 0 to infinity and maximum serum concentration were contained within the acceptance interval of 80%-125%. No clinically meaningful differences regarding overall safety, immunogenicity, and local tolerability were observed. Notably, after FYB202 administration, in fewer subjects at least 1 positive antidrug antibody result was observed compared to the reference groups (FYB202, 20%; EU-Ref, 42%; US-Ref, 51%). In conclusion, the RUSTIC trial demonstrated equivalent PK characteristics for FYB202 when compared to both EU-Ref and US-Ref ustekinumab and between both reference drugs. It provides the basis for the marketing authorization of FYB202, together with an extensive analytical characterization and the results of a confirmatory efficacy and safety trial in patients with moderate to severe plaque psoriasis.

Screening of psoriatic arthritis by dermatologists - a German nationwide survey.

BACKGROUND AND OBJECTIVES: Up to 30% of psoriasis (PsO) is clinically associated with psoriatic arthritis (PsA). A large proportion of new onset of PsA is diagnosed at a later stage, despite the necessity of early effective treatment to prevent structural damage. This study aimed to identify the routine screening practices used for PsA in patients with PsO. PATIENTS AND METHODS: This non-interventional, prospective, epidemiological, cross-sectional study conducted in Germany focuses on screening activity and treatment selection of dermatological practices in suspected PsA. Descriptive statistics and patient characteristics were analyzed for different center types. RESULTS: One hundred ninety-five patients from 34 office-based physicians, five non-university hospitals, and nine university hospitals were included. Questionnaires or imaging techniques were not routinely used (< 45%). Especially, ultrasounds (≤ 5%) and MRIs (< 6.3%) were rarely performed. Between 30% and 75% of suspected PsA could be confirmed. Referral to rheumatologists and/or appropriate therapy initiation were the most frequent consequences. CONCLUSIONS: Results of this study reflect the status of PsA screening activity by dermatologists. Imaging techniques, particularly ultrasound or MRIs to detect early forms of PsA, were inadequately used, which may have contributed to continued underdiagnoses. Collaboration between dermatologists and rheumatologists should be reviewed with a view to improving effective PsA screening.

Nailfold Capillaroscopy Findings in Patients With Psoriasis Vulgaris and Different Domains of Psoriatic Arthritis.

Background: Psoriasis is a chronic autoimmune disease with longtime activity and multisystem affection. Nailfold capillaroscopy (NC) is a simple noninvasive microscopic tool useful for identification of nailfold microvasculopathy. Objective: The present study aimed to compare NC findings in patients with psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) with different clinical domains. Methods: The present cross-sectional study included 200 psoriasis patients classified into five 40-patient groups: group I (GI) included PsA patients with predominant peripheral arthritis; group II (GII) included PsA patients with predominant peripheral arthritis and dactylitis and/or enthesitis; group III (GIII) included PsA patients with predominant axial affection; group IV (GIV) patients included PsA patients with predominant axial affection and dactylitis and/or enthesitis and group V (GV) included patients with PsV. In addition, there were 40 age and sex-matched healthy controls (GVI). Results: The studied patients had capillary density of 6.7 ± 3.5/mm with 90 patients (45.0 %) having reduced capillary density. GI-GIV patients had significantly lower capillary density and higher frequency of patients with reduced capillary density as compared to GV patients. The reported capillary dimension in the studied patients is 15.7 ± 7.9 µm and 55 patients (27.5 %) had large/giant capillaries. Patients in GV had significantly lower capillary dimension in comparison to GI-GIV patients. There were 64 patients (32.0 %) with abnormal capillary morphology and 47 patients (23.5 %) with capillary hemorrhages. Conclusions: PsA patients of all domains have lower capillary density and larger capillary dimensions as compared to PsV patients.

Biological therapy for psoriatic arthritis: current state and future perspectives.

Psoriatic arthritis is a medical condition that lies at the intersection of various fields of medicine, and its therapy always requires a comprehensive, holistic approach. Biological disease-modifying antirheumatic drugs (bDMARDs) constitute an extremely effective treatment method for PsA, provided that appropriate principles for patient qualification for the drug are followed, along with subsequent monitoring of the response to treatment. Based on their mechanisms of action, four main groups of bDMARDs used in PsA can be distinguished (TNF inhibitors, IL-12/23 and IL-23 inhibitors, IL-17 inhibitors, CTLA4 agonists). Clinical trials are ongoing in search of registration for additional bDMARDs, and the tasks for doctors and scientists worldwide include patient education, increasing treatment accessibility, and optimizing its costs.

The prevalence and clinical features of leflunomide-associated peripheral neuropathy in patients with rheumatic disease in a New Zealand cohort.

OBJECTIVE: To identify the prevalence and clinical features of leflunomide-associated peripheral neuropathy in patients with rheumatic disease over a 42-month observational period between January 1, 2016 and June 30, 2019. METHODS: A retrospective observational study was conducted using regional prescription data identifying all patients treated with leflunomide for rheumatic diseases in the Southern District Health Board of New Zealand. Medical records were used to identify patients who developed peripheral neuropathy while receiving treatment with leflunomide. Demographic characteristics, co-therapies, and additional risk factors for peripheral neuropathy were also recorded. RESULTS: A total of 482 patients were identified as receiving leflunomide for the treatment of rheumatic during the study period. In total, 23 patients developed leflunomide-induced peripheral neuropathy within the cohort giving a prevalence of 4.7%. Nerve conduction studies (NCS) performed in 18 (78.2%) of these patients confirmed a distal axonal, sensory, or sensorimotor peripheral neuropathy. The majority of patients (n = 22; 95.6%) either improved, stabilized, or resolved on cessation of the drug, with or without medication washout. Adverse symptoms were reported in association with peripheral neuropathy in 15 of the 23 patients (65.2%): these included pain, poor sleep, compromised skin integrity, poor balance, and a Charcot-like arthropathy. Additional treatment was required to manage symptoms of peripheral neuropathy including nine patients (39%) who received pain relief. CONCLUSIONS: This study supports the previously reported association between leflunomide treatment and the development of a peripheral neuropathy. However, our findings suggest that this is more common than the previous estimates. In patients with psoriatic arthritis and previous tarsitis, there appeared to be an association with a Charcot's-like arthropathy, a complication not previously noted in the literature.

Pain catastrophizing negatively impacts drug retention rate in patients with Psoriatic Arthritis and axial Spondyloarthritis: results from a 2-years perspective multicenter GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica) study.

BACKGROUND: Chronic pain and inflammation are common features of rheumatic conditions such as Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA), often needing prolonged medication treatment for effective management. Maintaining drug retention is essential for both achieving disease control and improving patients' quality of life. This study investigates the influence of pain catastrophizing, a psychological response to pain, on the drug retention rates of PsA and axSpA patients. METHODS: A two-year prospective multicenter observational study involved 135 PsA and 71 axSpA patients. Pain Catastrophizing Scale (PCS) was employed to assess pain catastrophizing. Univariable and multivariable regression analyses were utilized to identify factors associated with drug retention. RESULTS: In the PsA group, patients early discontinuing therapy showed higher baseline disease activity as well as higher incidence of comorbid fibromyalgia. Notably, pain catastrophizing, specifically the domains of Helplessness, Magnification, and Rumination, were significantly elevated in PsA patients who interrupted the treatment. Multivariable analysis confirmed pain catastrophizing as an independent predictor of drug suspension within two years. In axSpA, drug discontinuation was associated with female gender, shorter disease duration, higher baseline disease activity as well as elevated levels of pain catastrophizing. Univariable analysis supported the role of pain catastrophizing, including its domains, as predictors of treatment interruption. However, limited events in axSpA patients precluded a multivariate analysis. CONCLUSION: This prospective study emphasizes the impact of pain catastrophizing on drug retention in patients with PsA and axSpA.