EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update.

OBJECTIVE: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. METHODS: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. RESULTS: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. CONCLUSION: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients.

OBJECTIVES: The ASSIST study investigated prescribing in routine psoriatic arthritis (PsA) care and whether the patient reported outcome: PsA Impact of Disease questionnaire (PsAID-12), impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification. METHODS: Patients with PsA were selected across the UK and Europe between July 2021-March 2022. Patients completed the PsAID questionnaire, with the results shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded. RESULTS: 503 patients recruited. 36.2% had changes made to treatment, 88.8% of this had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; the PsAID-12 score was associated with odds of treatment escalation (OR: 1.58; p< 0.0001). However, most clinicians reported PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician's assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation, (OR = 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact. CONCLUSION: This study highlights multiple factors impacting treatment decision making for individuals with PsA. PsAID-12 scoring correlates with multiple measures of disease severity and odds of treatment escalation. However, most clinicians reported the PsAID-12 did not influence treatment escalation decisions. PsAID scoring could be used to increase confidence in treatment de-escalation.

Patients With Psoriatic Arthritis-Related Enthesitis and Persistence on Tofacitinib Under Real-World Conditions.

OBJECTIVE: Information on the persistence of tofacitinib (TOF) in psoriatic arthritis (PsA) is scarce in real-world conditions. Our objective was to analyze the persistence and safety of TOF under these conditions. METHODS: This was a single-center retrospective longitudinal observational study of all patients with PsA who received at least 1 dose of TOF. The main focus was on adverse events (AEs) and drug survival. Drug survival was analyzed by Kaplan-Meier curves and persistence explanatory factors by multivariate Cox regression models. The hazard ratio (HR) was used to measure association. RESULTS: Seventy-two patients were included, 54 women and 18 men, mean age 51.9 (SD 11.1) years, mean disease duration of 10.4 (SD 6.99) years. TOF was ≥ third line of therapy in > 70% of cases. The median survival was 13.0 (IQR 5.3-29.0) months. One-year retention rate was 52.7% (95% CI 42.4-65.6). TOF survival was not influenced by sex, disease duration, comorbidities, or line of treatment. Younger patients (HR 0.96, P = 0.01) and those with enthesitis (HR 0.37, P = 0.03) showed lower odds of drug discontinuation. The overall rate of AEs was 52.9 (95% CI 38.5-70.6)/100 person-years. Most AEs occurred during the first 6 months of exposure. CONCLUSION: In this real-world study, TOF showed a reasonably good retention rate in a PsA population that was mostly refractory to biologic and oral targeted synthetic disease-modifying antirheumatic drugs. There were no new causes for concern regarding safety. Patients with refractory PsA and enthesitis might be a specific target population for this drug.

Core items to be included in a definition of moderate psoriatic arthritis: literature review and expert opinion.

Evidence-based treatment recommendations for psoriatic arthritis (PsA) suggest that treatment should be individualised but acknowledge the difficulty of correctly defining levels of activity (mild, moderate and severe). The aim of this study was to define the parameters or disease characteristics that should be included in a future definition of moderate PsA. Mixed. methods: (1) literature review to identify previous assessment tools used to classify patients into mild, moderate and severe forms, and (2) survey of rheumatologists, and experts in PsA, to obtain their opinion on the degree of validation and applicability of published definitions and tools, and on the parameters that should be included in a future definition of moderate PsA. We propose eight domains/items to be included in a definition of moderate PsA: number of active joints and inflamed entheses, physician global assessment (by visual analogue scale), dactylitis, body surface area (BSA) affected by psoriasis, psoriasis in special locations, and absence of hip involvement. The Disease Activity Index for Psoriatic Arthritis (DAPSA) score would be supported as part of this definition, as would the Psoriatic Arthritis Impact of Disease (PsAID) index. This study proposes a set of items/domains to be included in a definition of moderate PsA based on literature and expert opinion, which can be the starting point for further development and validation studies of the proposed items.

EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis.

BACKGROUND: The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. OBJECTIVE: To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. METHODS: A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. RESULTS: Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. CONCLUSION: These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development.

An international multi-centre analysis of current prescribing practices and shared decision-making in psoriatic arthritis.

OBJECTIVES: Shared decision-making (SDM) is advocated to improve patient outcomes in Psoriatic arthritis (PsA). We analysed current prescribing practices and the extent of SDM in PsA across Europe. METHODS: The ASSIST study was a cross-sectional observational study of PsA patients aged ≥18 years attending face-to-face appointments between July 2021-March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician's effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). RESULTS: 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. CONCLUSIONS: Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT05171270.

Confounders contributing to explain the association between sex and disease impact in patients with recent-onset psoriatic arthritis.

OBJECTIVES: To evaluate the effect of potential confounders on the association between sex and disease impact in recent-onset psoriatic arthritis. METHODS: We performed a multicentre observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. The dataset was generated using data for each patient at the 3 visits (baseline, first year, and second year of follow-up) matched with the PsAID values at each of the 3 visits. Once variables associated with both PsAID ≥4 and sex were selected, those that led to a difference of >10% between the adjusted and crude estimations were identified as potential confounders in the association between sex and PsAID. Lastly, the final multivariate logistic regression model estimating the association between sex and PsAID was defined. RESULTS: The dataset contained 418 observations (158 at baseline, 135 at the first follow-up visit, and 125 at the second visit). The confounders identified in the multivariate model were HAQ, global pain, level of physical activity, and joint pattern at diagnosis. After adjustment for these variables, no statistically significant association was observed between female sex and PsAID ≥4. CONCLUSIONS: The association between female sex and greater disease impact could be explained by the influence of other variables, specifically higher HAQ score, greater intensity of pain, differences in the level of physical activity and in the joint pattern at diagnosis (lower frequency of the spondylitis pattern in women).

The IFIH1/MDA5 rs1990760 Gene Variant (946Thr) Differentiates Early- vs. Late-Onset Skin Disease and Increases the Risk of Arthritis in a Spanish Cohort of Psoriasis.

The melanoma differentiation-associated protein 5 (MDA5; encoded by the IFIH1 gene) mediates the activation of the interferon pathway in response to a viral infection. This protein is also upregulated in autoimmune diseases and psoriasis skin lesions. IFIH1 gene variants that increase MDA5 activity have been associated with an increased risk for immune-mediated diseases, including psoriasis. Our aim is to determine the association between three IFIH1 variants (rs35337543 G/C, intron8 + 1; rs35744605 C/A, Glu627Stop; and rs1990760 C/T, Ala946Thr) and the main clinical findings in a cohort of Spanish patients with psoriasis (N = 572; 77% early-onset). Early-onset psoriasis patients (EOPs) had a significantly higher frequency of severe disease and the Cw6*0602 allele. Carriers of rs1990760 T (946Thr) were more common in the EOPs (p < 0.001), and the effect was more pronounced among Cw6*0602-negatives. This variant was also associated with an increased risk of psoriatic arthritis (PsA) independent from other factors (OR = 1.62, 95%CI = 1.11-2.37). The rs3533754 and rs35744605 polymorphisms did not show significant differences between the two onset age or PsA groups. Compared to the controls, the 946Thr variant was more common in the EOPs (nonsignificant difference) and significantly less common in patients aged >40 years (p = 0.005). In conclusion, the common IFIH1 rs1990760 T allele was significantly more frequent in early-onset compared to late-onset patients. This variant was also an independent risk factor for PsA in our cohort. Our study reinforces the widely reported role of the IFIH1 gene variants on psoriatic disease.

Construct validity of the ASAS health index in psoriatic arthritis: a cross-sectional analysis.

OBJECTIVES: The Assessment of SpondyloArthritis international Society health index (ASAS-HI) was designed to assess the global health of patients with spondyloarthritis, but its performance in psoriatic arthritis (PsA) is hardly known. We addressed the clinimetric properties of this instrument in patients with PsA. METHODS: This was a cross-sectional observational study that included 90 consecutive patients with PsA. The measurement properties of ASAS-HI were analysed against the Disease Activity index for PSoriatic Arthritis (DAPSA) and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. A multivariate analysis was performed to weigh the ASAS-HI items associated with DAPSA active disease and PsAID high impact. RESULTS: Mean ASAS-HI was 5.8 (4.3). Convergent validity was high both against DAPSA (ρ 0.78, P < 0.0001) and PsAID (ρ 0.80, P < 0.0001). ASAS-HI showed a high discriminant capacity for both DAPSA remission [optimal criterion ≤ 2, area under the receiver operating characteristic curve (AUC) 0.92 (95% CI: 0.85, 0.97), P < 0.0001], and low activity [optimal criterion ≤6, AUC 0.87 (95% CI: 0.79, 0.94), P < 0.0001]. The ASAS-HI items significantly associated with DAPSA active disease were: 'I find it hard to stand for long' (ß 4.48, P < 0.0001), 'I find it hard to concentrate' (ß 2.94, P = 0.042) and 'I sleep badly at night' (ß 1.86, P = 0.044). As for PsAID, the only item significantly associated with a high impact was 'I sleep badly at night' (ß -3.29, P = 0.015). CONCLUSION: We demonstrated construct validity of ASAS-HI, a spondyloarthritis instrument, for the assessment of global health in patients with PsA.

Management of particular clinical situations in psoriatic arthritis: an expert's recommendation document based on systematic literature review and extended Delphi process.

To establish practical recommendations for the management of patients with psoriatic arthritis (PsA) with particular clinical situations that might lead to doubts in the pharmacological decision-making. A group of six expert rheumatologists on PsA identified particular clinical situations in PsA. Then, a systematic literature review (SLR) was performed to analyse the efficacy and safety of csDMARDs, b/tsDMARDs in PsA. In a nominal group meeting, the results of the SLR were discussed and a set of recommendations were proposed for a Delphi process. A total of 65 rheumatologists were invited to participate in the Delphi. Agreement was defined if ≥ 70% of the participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grade of recommendation was established based on the Oxford Evidence-Based Medicine categorisation. Particular clinical situations included monoarthritis, axial disease, or non-musculoskeletal manifestations. The SLR finally comprised 131 articles. A total of 16 recommendations were generated, all but 1 reached consensus. According to them, it is crucial to carefully analyse the impact of individual manifestations on patients (disability, quality of life, etc.), but also to recognise the impact of each drug singularities on selected clinical phenotypes to adopt the most appropriate treatment strategy. Early diagnosis and treatment to target approach, along with a close risk management, is also necessary. These recommendations are intended to complement gaps in national and international guidelines by helping health professionals address and manage particular clinical situations in PsA.

Genetic Variants of the NF-κB Pathway: Unraveling the Genetic Architecture of Psoriatic Disease.

Psoriasis is a multifactorial genetic disease for which the genetic factors explain about 70% of disease susceptibility. Up to 30-40% of psoriasis patients develop psoriatic arthritis (PsA). However, PsA can be considered as a "disease within a disease", since in most cases psoriasis is already present when joint complaints begin. This has made studies that attempt to unravel the genetic basis for both components of psoriatic disease enormously difficult. Psoriatic disease is also accompanied by a high burden of comorbid conditions, mainly of the cardiometabolic type. It is currently unclear whether these comorbidities and psoriatic disease have a shared genetic basis or not. The nuclear factor of kappa light chain enhancer of activated B cells (NF-κB) is a transcription factor that regulates a plethora of genes in response to infection, inflammation, and a wide variety of stimuli on several cell types. This mini-review is focused on recent findings that highlight the importance of this pathway both in the susceptibility and in the determinism of some features of psoriatic disease. We also briefly review the importance of genetic variants of this pathway as biomarkers of pharmacological response. All the above may help to better understand the etiopathogenesis of this complex entity.

Mismatch between the impact of disease perceived by patients and the state of clinical remission assessed by physicians in psoriatic arthritis.

OBJECTIVES: Both the evaluation of disease activity and the assessment of the impact of the disease on patients' lives are subjects of intense research at present in psoriatic arthritis (PsA). We aimed to test the degree of concordance between the impact of the disease and the state of clinical remission defined by physicians in PsA. METHODS: We conducted a post hoc analysis of a multicentre study that analysed 223 PsA patients treated with remission-inducing systemic drugs. Clinical remission was assessed by the Disease Activity in Psoriatic Arthritis (DAPSA) score and by the opinion of the evaluating physician (specific question yes/no). A patient-acceptable symptom state (PASS) corresponded to a Psoriatic Arthritis Impact of Disease (PsAID) value less than 4. The degree of agreement between remission and PASS was estimated by the Cohen's kappa (κ) index. RESULTS: The degree of agreement between remission judged by physicians and the PASS status was low (κ: 0.16). There was a moderate agreement (κ: 0.46) between DAPSA remission and PASS, while there was almost a good concordance (κ: 0.58) between clinical DAPSA (without C-reactive protein) remission and PASS. CONCLUSIONS: We found a clear disagreement between the impact of illness perceived by the patient with PsA and clinical remission judged by physicians. Therefore, clinical and treatment decision-making in PsA should be based more on composite indexes (DAPSA) than on the perceptions of treating physicians.

Good clinimetric alignment between remission and a low impact of disease in patients with axial psoriatic arthritis.

OBJECTIVES: The concept of axial disease in psoriatic arthritis (PsA) is not well established. It is also unclear how this disease domain should be evaluated. We aimed to test whether the remission is aligned with a low impact state of the disease in patients with axial PsA. METHODS: Post hoc analysis of a multicentre study conducted in 223 patients with PsA under treatment with systemic biological and non-biological therapies. To define axial disease, ASAS criteria were used. Remission corresponded to a BASDAI less than or equal to 2. The impact of the disease was evaluated according to the PsAID. The Cohen's kappa agreement between remission and patient-acceptable symptoms state (PASS) was analysed. RESULTS: Thirty-seven of the 223 patients (16.6%) met ASAS criteria for axial disease. Fifteen of the 122 (12.3%) patients in PASS situation had axial disease compared to 22 of 101 (21.8%) who did not reach this state, p<0.05. All items, as well as the total score of the BASDAI (4.48±2.03 vs. 1.14±1.02) were significantly higher in the patients who did not achieve a PASS, p<0.001. The kappa agreement between BASDAI remission and PASS was high [κ: 0.73 (95%CI: 0.64-0.83) p<0.0001]. CONCLUSIONS: BASDAI remission and a low impact of the disease show good clinimetric alignment. Both measures could be useful for a more comprehensive assessment of axial disease in PsA.

Disease Activity in Psoriatic Arthritis Index and Psoriatic Arthritis Impact of Disease Questionnaire: correlation and sensitivity to change in a real clinical setting.

OBJECTIVES: The performance of many outcome measures for psoriatic arthritis (PsA) is almost unknown in real clinical practice. Our objective was to study the correlation and sensitivity to change of the Disease Activity in Psoriatic Arthritis (DAPSA) index and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire in a real practice setting. METHODS: This was a prospective, open, non-controlled study that included 60 consecutive patients with PsA treated with ustekinumab. Most had been previously treated with one or more biologic therapeutic agents. The correlation (Spearman's rho coefficient) and the sensitivity to change [Standardized Mean Response (SMR)] of DAPSA and PsAID were studied. Effect size values of 0.20, 0.50 and 0.80 corresponded to low, moderate and high sensitivity to change, respectively. RESULTS: More than 70% of patients achieved therapeutic goals (21.7% were in remission and 50% in low disease activity according to DAPSA categories). Two out of three patients reached an acceptable symptomatic state (PsAID <4). The correlation between final values of both instruments was substantial (Spearman's rho: 0.62, p<0.0001). The SMR for the PsAID was 1.08 (0.95-1.21) and for DAPSA was 1.5 (1.37-1.63), both values corresponding to instruments with a high sensitivity to change (>0.80). The best PsAID cut-off value for identifying DAPSA remission was 3.32 with an area under the ROC curve of 0.82. CONCLUSIONS: DAPSA and PsAID seem to be useful instruments for a more comprehensive assessment of PsA in daily practice. Our results can help to disseminate the use of these instruments in the clinical practice of many rheumatologists.

Evaluating standards of care in psoriatic arthritis of the QUANTUM project (qualitative initiative to improve outcomes): results of an accreditation project in Spain.

In Spain, the QUANTUM project has been promoted to reduce variability in clinical practice and improve the care and quality of life of people with psoriatic arthritis (PsA) by accrediting PsA units throughout the Spanish national health system. To present the results of this approach which sought to ensure an optimum level of quality for patients with PsA. Descriptive analysis of the self-assessments that the PsA units have carried out assessing their degree of compliance with the quality standards established in the QUANTUM project grouped into four blocks: shortening time to diagnosis; optimizing disease management; improving multidisciplinary collaboration; and improving patient monitoring. A total of 41 PsA units were self-evaluated. They met 64.1% of the defined quality standards. Optimize disease management obtained a higher level of standards compliance (72%) and improve multidisciplinary collaboration the lesser (63.9%). Accessibility to the treatments available for PsA in all hospitals was guaranteed (100%). Appropriate diagnostic equipment is available (97.6%). Compliance with specific quality standards leads to detect actions that should be implemented: quality of life assessment (9.8%), locomotor system assessment (12.2%), physical examination data record (14.6%), periodic cardiovascular risk assessment (17.1%). The QUANTUM project results make it possible to visualise how to care for patients with PsA is being developed in Spain. Problems identified in recent multinational reports are also identified in Spain.

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.