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.

Differences in treatment response between female and male psoriatic arthritis patients during IL-12/23 therapy with or without methotrexate: post hoc analysis of results from the randomised MUST trial.

BACKGROUND: The influence of sex on treatment outcomes during interleukin-12/23 therapy in patients with psoriatic arthritis (PsA) has not been explored. OBJECTIVE: To conduct exploratory post hoc analyses of sex-stratified data from the MUST trial, an investigator-initiated, multicentre, phase 3b study in which patients with active PsA initiating treatment with open-label ustekinumab were randomised to treatment with placebo or methotrexate (MTX). METHODS: We evaluated baseline characteristics, key treatment outcomes and adverse events stratified by sex, with a focus on outcomes that did not include erythrocyte sedimentation rate (ESR) as a component due to the known elevation of ESR in females. RESULTS: A total of 166 patients were treated with ustekinumab+MTX (37 female, 50 male) or ustekinumab+placebo (32 female, 47 male). At baseline, females had a significantly longer time since PsA diagnosis and greater impairment in physical function, but similar joint counts. At week 24, both females and males showed marked improvements to ustekinumab with or without MTX. Females generally had numerically reduced treatment responses compared with males, although differences did not achieve statistical significance. MTX did not show an overall effect on treatment outcomes, but was associated with faster enthesitis responses in males only. Adverse events were generally comparable, but females in the ustekinumab+MTX group had higher levels of gastrointestinal disorders. CONCLUSION: Females and males with PsA had differences in baseline characteristics, treatment responses and adverse events during therapy. A better understanding of sex-based differences in PsA may help optimise treatment.

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.

Association between biological immunotherapy for psoriasis and time to incident inflammatory arthritis: limitations and opportunities.

Psoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease that affects approximately 30% of psoriasis patients. In most cases, skin disease clearly precedes the musculoskeletal disease. Some studies suggest that targeted treatment may intercept the disease course and prevent psoriasis patients from developing PsA. A recent population-based retrospective analysis in 15 501 psoriasis patients evaluated the association between different biological treatment strategies and time to incident inflammatory arthritis based on data in a US electronic health records database. A cumulative incidence of 2.6 PsA cases per 100 person-years was determined. The multivariable regression analysis revealed a significantly lower risk of developing inflammatory arthritis in patients who had been prescribed interleukin (IL)-12/23 or IL-23 inhibitors compared with tumour necrosis factor (TNF) inhibitor-treated patients, whereas there was no significant difference in risk for patients prescribed inhibitors of IL-17 versus TNF. Although the analysis was based on a large set of clinical data and the findings were rigorously evaluated, there are some limitations in interpretation due to the study design. Prospective clinical trials are missing, and retrospective data analyses from clinical trials or population-based studies show conflicting results. Overall, the recent data on prevention of PsA in patients with psoriasis support the high need to characterise biomarkers of increased risk and perform prospective clinical trials to give a clear guidance on possibilities for disease interception in psoriatic disease.

Application of clinical and molecular profiling data to improve patient outcomes in psoriatic arthritis.

Achieving a good outcome for a person with Psoriatic Arthritis (PsA) is made difficult by late diagnosis, heterogenous clinical disease expression and in many cases, failure to adequately suppress inflammatory disease features. Single-centre studies have certainly contributed to our understanding of disease pathogenesis, but to adequately address the major areas of unmet need, multi-partner, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient-representative organizations. In this review, the ambitious programme of work to be undertaken by HIPPOCRATES is outlined and common approaches and challenges are identified. It is expected that, when completed, the results will ultimately allow for changes in the approaches to diagnosing, managing and treating PsA allowing for better short-term and long-term outcomes.

Improving outcomes in Psoriatic Arthritis Psoriatic Arthritis (PsA) is a form of arthritis which is found in approximately 30% of people who have the skin condition, Psoriasis. Frequently debilitating and progressive, achieving a good outcome for a person with PsA is made difficult by late diagnosis, disease clinical features and in many cases, failure to adequately control features of inflammation. Research studies from individual centres have certainly contributed to our understanding of why people develop PsA but to adequately address the major areas of unmet need, multi-centre, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient representative organisations (see appendix). In this review, the ambitious programme of work to be undertaken by HIPPOCRATES is outlined and common approaches and challenges are identified. The participation of patient research partners in all stages of the work of HIPPOCRATES is highlighted. It is expected that, when completed, the results will ultimately allow for changes in the approaches to diagnosing, managing and treating PsA allowing for improvements in short-term and long-term outcomes.

Management of Enthesitis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Enthesitis is a key pathological and clinical feature of psoriatic arthritis (PsA) in children and adults. Enthesitis is typically assessed clinically using several validated enthesitis scoring systems that have been used in clinical trials. Enthesitis treatment response has been reported as change in the total enthesitis score or the proportion of patients who achieved complete resolution. The majority of trials in PsA did not require patients to have enthesitis at study entry since enthesitis was evaluated only as a secondary outcome. Despite the inherent limitations of the clinical assessment of enthesitis, imaging of the entheses using ultrasound or magnetic resonance imaging has rarely been used in clinical trials to assess response to treatment of enthesitis. This systematic review summarizes existing evidence regarding pharmaceutical and nonpharmaceutical interventions for enthesitis in patients with PsA to facilitate an evidence-based update of the Group for Research and Assessment in Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for PsA. METHODS: We performed a systematic literature review to identify 41 randomized clinical trials that reported enthesitis treatment response in patients with PsA. For each intervention, the response effect size was summarized and the quality of evidence was graded. Recommendations were then formulated for the various pharmacological and nonpharmacological therapies. RESULTS: We included 41 randomized clinical trials in our review and graded each intervention. CONCLUSION: Several classes of systemic conventional and advanced therapies and local measures were recommended for active enthesitis in patients with PsA.

Omics and Multi-Omics Analysis for the Early Identification and Improved Outcome of Patients with Psoriatic Arthritis.

The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent. As with other IMIDs, the detection of multimodal molecular biomarkers offers some hope for the early diagnosis of PsA and the initiation of effective management and treatment strategies. However, specific biomarkers are not yet available for PsA. The assessment of new markers by genomic and epigenomic profiling, or the analysis of blood and synovial fluid/tissue samples using proteomics, metabolomics and lipidomics, provides hope that complex molecular biomarker profiles could be developed to diagnose PsA. Importantly, the integration of these markers with high-throughput histology, imaging and standardized clinical assessment data provides an important opportunity to develop molecular profiles that could improve the diagnosis of PsA, predict its occurrence in cohorts of individuals with psoriasis, differentiate PsA from other IMIDs, and improve therapeutic responses. In this review, we consider the technologies that are currently deployed in the EU IMI2 project HIPPOCRATES to define biomarker profiles specific for PsA and discuss the advantages of combining multi-omics data to improve the outcome of PsA patients.

Fluorescence-optical imaging as a promising easy-to-use imaging biomarker to increase early psoriatic arthritis detection in patients with psoriasis: a cross-sectional cohort study with follow-up.

OBJECTIVES: To evaluate the ability of fluorescence-optical imaging (FOI) to detect preclinical musculoskeletal inflammatory signs in patients with skin psoriasis at risk of developing psoriatic arthritis (PsA). METHODS: This investigator-initiated prospective exploratory study evaluated adult patients with psoriasis with musculoskeletal complaints and/or nail psoriasis within the last 6 months. Patients underwent a comprehensive rheumatological clinical examination (CE) along with musculoskeletal ultrasound (MSUS) and FOI of both hands at a single visit. Patients with CE-/MSUS-/FOI+ findings had MRI performed on the symptomatic or dominant hand within 7 days. If MRI was negative, the patients were followed over 2 years for the onset of clinically manifest PsA. RESULTS: A total of 389 patients were referred from dermatology centres and evaluated at 14 rheumatology sites in Germany. Seventy-seven (20%) patients with CE-/US-/FOI- were considered to have psoriasis only. PsA was diagnosed in 140/389 patients (36%) based on CE alone and in another 55 patients (14%) by additional MSUS; overall, 50% of the patient cohort was diagnosed with PsA. One hundred sixteen patients (30%) were FOI+ (CE-) of which 40 (37%) were FOI+/MRI+. In the 2-year follow-up of the FOI+/CE- patients, clinical PsA was confirmed in another 12%. CONCLUSION: FOI is a promising method for the detection of signs of musculoskeletal inflammation in hands that may serve as an early imaging biomarker for transitions from psoriasis to PsA. This imaging technique has the potential to detect PsA in at-risk patients with psoriasis, reduce time to PsA diagnosis and improve patient outcomes.

Does concomitant methotrexate confer clinical benefits in patients treated with prior biologic therapy? Analysis of data from a noninterventional study of rheumatoid arthritis patients initiating treatment with adalimumab.

Most studies of methotrexate (MTX) in combination with tumor necrosis factor (TNF) inhibitors have focused on treatment-naive patients with early disease. The goal of this study was to evaluate whether previous biologic therapy influenced the impact of concomitant MTX in patients initiating treatment with adalimumab.We retrospectively analyzed data from 2 large noninterventional studies of German patients with active rheumatoid arthritis (RA) who initiated adalimumab therapy during routine clinical practice. Patients were seen between April 2004 and February 2013 for study 1 and between April 2003 and March 2013 for study 2. Key outcomes were Disease Activity Score-28 joints (DAS28), patient global assessment of health (PGA), and pain. Subgroup analyses by prior biologic treatment were performed on patients treated with continuous adalimumab monotherapy or adalimumab plus MTX for 12 months and 2-sample t tests were used to evaluate differences. We also assessed outcomes in subgroups in which MTX had been added or removed at 6 months and compared outcomes with 1-sample t tests.Of 2654 patients, 1911 (72%) were biologic naive and 743 (28%) had received prior biologic therapy, usually with a TNF inhibitor. All subgroups showed improvements following initiation of adalimumab therapy. In patients with no previous biologic treatment, continuous adalimumab plus MTX was associated with greater improvements in DAS28, PGA, and pain at month 12 compared with continuous adalimumab monotherapy (P = .0006, .0031, and .0032, respectively). In patients with previous biologic treatment, concomitant MTX was associated with statistically significant benefits in pain only. Adding MTX at month 6 resulted in additional benefits in patients with no prior biologic therapy, but not those with previous biologics.We conclude that concomitant MTX resulted in additional improvements in DAS28 and PGA vs adalimumab monotherapy in patients with no previous biologic therapy, but changes were not statistically significant in patients treated with prior biologics. These findings may help inform the patient/provider treatment decision during routine clinical care.

Individual therapeutic DAS28-dcrit responses differentiate between effectiveness of rheumatoid arthritis therapies and reflect patient-reported outcomes: retrospective analysis of DAS28 responses in comparative tocilizumab studies.

Assessment of individual therapeutic responses provides valuable information concerning treatment benefits in individual patients. We evaluated individual therapeutic responses as determined by the Disease Activity Score-28 joints critical difference for improvement (DAS28-dcrit) in rheumatoid arthritis (RA) patients treated with intravenous tocilizumab or comparator anti-tumor necrosis factor (TNF) agents. The previously published DAS28-dcrit value [DAS28 decrease (improvement) ≥ 1.8] was retrospectively applied to data from two studies of tocilizumab in RA, the 52-week ACT-iON observational study and the 24-week ADACTA randomized study. Data were compared within (not between) studies. DAS28 was calculated with erythrocyte sedimentation rate as the inflammatory marker. Stability of DAS28-dcrit responses and European League Against Rheumatism (EULAR) good responses was determined by evaluating repeated responses at subsequent timepoints. A logistic regression model was used to calculate p values for differences in response rates between active agents. Patient-reported outcomes (PROs; pain, global health, function, and fatigue) in DAS28-dcrit responder versus non-responder groups were compared with an ANCOVA model. DAS28-dcrit individual response rates were 78.2% in tocilizumab-treated patients and 58.2% in anti-TNF-treated patients at week 52 in the ACT-ion study (p = 0.0001) and 90.1% versus 59.1% at week 24 in the ADACTA study (p < 0.0001). DAS28-dcrit responses showed greater stability over time (up to 52 weeks) than EULAR good responses. For both active treatments, DAS28-dcrit responses were associated with statistically significant improvements in mean PRO values compared with non-responders. The DAS28-dcrit response criterion provides robust assessments of individual responses to RA therapy and may be useful for discriminating between active agents in clinical studies and guiding treat-to-target decisions in daily practice.

Minimal disease activity is a stable measure of therapeutic response in psoriatic arthritis patients receiving treatment with adalimumab.

Objective: The aim of this study was to evaluate minimal disease activity (MDA) assessments in patients with PsA during routine clinical care. Methods: We used data from a multicentre observational study of patients with active PsA who initiated treatment with adalimumab during routine clinical practice and continued treatment for at least 6 months to evaluate achievement of MDA, individual MDA criteria (modified to conform to study assessments) and ACR responses during 24 months of therapy. Pearson correlation coefficients were used to evaluate the association between MDA and individual criteria at month 6; regression models were used to determine the influence of baseline MDA criteria on achievement of MDA at month 6. Results: A total of 1684 patients were included in these analyses; most had long-standing disease. MDA was achieved by 597 patients (35.5%) at month 6. This proportion increased to 45.5% at month 24 in patients remaining on therapy. MDA status was stable over time; >75% of patients with MDA at month 6 recorded MDA at subsequent visits. Pain was the most difficult individual criterion to achieve, and enthesitis was the least difficult. Higher functional status and fewer tender joints at baseline predicted achievement of MDA at month 6. About half of patients (51.5%) with an ACR20 response at month 6 achieved MDA. Conclusion: In this observational cohort of patients with long-standing disease, MDA provided a stable and valid assessment of clinical status over 24 months. Trial registration: Clinicaltrials.gov, https://clinicaltrials.gov, NCT01111240.

Anti-citrullinated protein antibodies are linked to erosive disease in an observational study of patients with psoriatic arthritis.

OBJECTIVE: ACPAs are associated with bone destruction in RA. The aim of this study was to evaluate the association between ACPA and bone destruction in patients with a distinct inflammatory disorder, PsA. METHODS: We used baseline data from a large observational study of PsA patients preparing to initiate treatment with adalimumab to analyse demographic and disease characteristics by ACPA status. To ensure a homogeneous PsA study population, only patients with active psoriatic skin manifestations who met Classification of Psoriatic Arthritis criteria for PsA were included in the analyses, thereby minimizing the risk of including misdiagnosed RA patients. Multiple logistic regression analyses were used to explore potential associations between ACPA seropositivity and bone destruction. RESULTS: Of 1996 PsA patients who met the strict inclusion criteria, 105 (5.3%) were positive for ACPA. ACPA-positive patients had significantly higher swollen joint counts and 28-joint DAS values than ACPA-negative patients and significantly higher rates of erosive changes and dactylitis. Multiple logistic regression analysis confirmed the association of ACPA seropositivity with a 2.8-fold increase in the risk of erosive disease. CONCLUSION: As has been previously shown for RA, ACPA is associated with bone destruction in PsA, suggesting that the osteocatabolic effect of ACPA is not confined to RA but is also detectable in the different pathogenetic context of a distinct disease entity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01111240.

Does Concomitant Methotrexate with Adalimumab Influence Treatment Outcomes in Patients with Psoriatic Arthritis? Data from a Large Observational Study.

OBJECTIVE: To examine the influence of concomitant methotrexate (MTX) with adalimumab (ADA) on outcomes in patients with psoriatic arthritis (PsA) using data from an observational study of ADA. METHODS: Data from a German noninterventional study of patients with PsA starting treatment with ADA were analyzed retrospectively for effects of concomitant MTX on key outcomes, including Disease Activity Score-28 joints, tender and swollen joint counts, skin assessments, and safety. Patients were categorized into those with symptoms of axial involvement and those with no symptoms of axial involvement as judged by the examining clinician. RESULTS: A total of 1455 patients met the study criteria, 296 with axial involvement (ADA monotherapy = 165; plus MTX = 131) and 1159 with no axial involvement (ADA monotherapy = 658; plus MTX = 501). ADA, alone or combined with MTX, resulted in strong and comparable reductions in disease activity measures in patients with and those without axial disease over 24 months of therapy. In multiple regression analyses, concomitant MTX did not affect joint or skin outcomes in either the group with axial manifestations or the group without axial disease. Neither adverse event rates nor withdrawal rates were significantly influenced by concomitant MTX. CONCLUSION: ADA is an effective treatment option for patients with PsA with or without axial involvement. Compared with ADA monotherapy, the use of concomitant MTX with ADA does not improve articular or skin outcomes in patients with PsA regardless of axial symptoms. TRIAL REGISTRATION: Clinicaltrials.gov NCT01111240.

Update 2011: leflunomide in rheumatoid arthritis - strengths and weaknesses.

PURPOSE OF REVIEW: Leflunomide is often used as a first choice disease-modifying antirheumatic drug after methotrexate. New data are available for efficacy and safety in both, monotherapy and combination with biologicals. RECENT FINDINGS: New data on efficacy demonstrate comparable effect sizes for leflunomide and methotrexate in the treatment of signs and symptoms in combination with tumour necrosis factor-blocking agents and rituximab. Equipotency has also been demonstrated by a recent radiographic outcome study on methotrexate and leflunomide monotherapy. Pharmacogenetic studies indicate an impact of polymorphisms on the variability in serum levels of the compound with potential relevance to effectiveness and tolerability in individual patients. Genetic factors are also likely to contribute to the significantly increased risk for leflunomide-induced pulmonary disease reported in Asia. Because pre-existing interstitial lung disease as well as methotrexate-induced pneumonitis have been identified as risk factors for leflunomide-induced pulmonary disease, the use of leflunomide as an alternative to methotrexate is limited under these conditions. SUMMARY: Effectiveness of leflunomide renders it a potent treatment option in rheumatoid arthritis. The known tolerability issues resulting in a less favourable adherence to therapy constitutes a weakness. However, documented data from large registries indicate that leflunomide is safe as far as the contraindications and recommendations for monitoring are regarded.