Elevating the Standard of Care for Patients with Psoriatic Arthritis: 'Calls to Action' from a Multistakeholder Pan-European Initiative.

INTRODUCTION: Psoriatic arthritis (PsA) is a complex, progressive, and often debilitating disease. Despite recent advances in treatment, numerous unmet needs in patient care persist. Rheumacensus is a multistakeholder, pan-European initiative designed to identify ways to elevate the standard of care (SoC) and treatment ambition for patients with PsA, using the perspectives of three key stakeholder groups: patients, healthcare professionals (HCPs) and payors. METHODS: Rheumacensus followed three phases: an insights-gathering workshop to identify current unmet needs in PsA and an area of focus for the project, a modified Delphi process to gain consensus on improvements within the agreed area of focus, and a Consensus Council (CC) meeting which used consensus statements as inspiration to generate 'Calls to Action' (CTA)-practical measures which, if implemented, could elevate the SoC for patients with PsA. RESULTS: The Rheumacensus CC consisted of four patient representatives, four HCPs and four payors. All 12 members completed all three Delphi e-consultations. The shared area of focus that informed the Delphi process was "patient empowerment through education on the disease and treatment options available, to enable patient involvement in management". Four key themes emerged from the Delphi process: patient empowerment, patient knowledge and sources of education, patient-HCP consultations, and optimal initial treatment. Statements within these themes informed 12 overarching CTA, which focus on the need for a multistakeholder approach to implementing a paradigm shift towards patient-centred care and improved outcomes for patients with PsA. CONCLUSION: Rheumacensus has identified shortcomings in the current SoC for patients with PsA and provides a foundation for change through practical CTA. It is hoped that all stakeholders will now take practical steps towards implementing these CTA across Europe to elevate the SoC for patients with PsA.

Inequalities in the care patients with psoriatic arthritis (PsA) receive can be mainly explained by poorly coordinated management due to a lack of disease and treatment knowledge. This report is about a programme called Rheumacensus which has the overall aim of improving the standard of care (SoC) for patients with PsA. Rheumacensus brings together the points of view of three key groups involved in the care of people with PsA: patients, payors and healthcare professionals (HCPs) from across Europe. Together, these three groups agreed to focus on patient empowerment through education on the disease and treatment options as a way to raise the SoC. Through a series of exercises­to agree on the current SoC and what needs to be improved­and group discussions, four themes were established which were used by the groups to help them suggest 'Calls to action' (CTA). The CTAs were ideas of how improvements could be made or what needs to be done to improve the care patients receive. The four themes were (1) patient empowerment, (2) patient knowledge, (3) patient­HCP consultation and (4) optimal initial treatment. In total, 12 CTAs were developed across these themes that provide direction and practical next steps which patients, payors and HCPs could take to drive change and make a real difference to patients by improving their care.

Lipid profile and NT-proBNP changes from pre-clinical to established rheumatoid arthritis: A 12 years follow-up explorative study.

OBJECTIVES: The aim of the current study was to explore the changes in lipid and NT-proBNP levels in rheumatoid arthritis (RA) patients through different phases of the disease: from the pre-clinical stage and RA onset up to the treatment phase with biological disease-modifying anti-rheumatic drugs (bDMARDS). METHODS: Thirty-eight consecutive patients, initially with arthralgia and rheumatoid factor and/or anti-citrullinated protein antibodies without arthritis, who later developed RA and eventually started treatment with bDMARDs, were included. Lipid spectrum and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured longitudinally from several months before diagnosis through treatment with bDMARDs. RESULTS: From baseline, C-reactive protein (CPR) initially increased sharply, decreasing with the start of biological treatment. Low-density lipoprotein-cholesterol (LDL-c) remained stable, high-density lipoprotein-cholesterol (HDL-c) increased, apolipoprotein A1 (ApoA1 and lipoprotein (a) (Lp(a)), and total cholesterol (TC)/HDL-c ratio and apolipoprotein B (ApoB) decreased during follow-up. NT-proBNP closely followed progression of CRP. TC, LDL-c, TC/HDL-c ratio, ApoA and ApoB inverse correlated with CRP, while Lp(a) positively correlated. HDL-c and triglycerides showed no correlation. CONCLUSION: Changes in the lipid profile and NT-proBNP in RA patients seem to be related to inflammation, with changes reflecting an increase in CVD risk occurring along with rises in CRP levels. These changes seem to already be present at diagnosis, indicating the need for timely control of inflammation.

Cardiovascular disease risk in patients with inflammatory arthritis nowadays still substantially elevated.

OBJECTIVES: This study aims to assess current cardiovascular disease risk and prevalence of risk factors in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (SpA). METHODS: 2050 consecutive patients with inflammatory arthritis (IA) and 939 controls were included, with 1308 patients with RA, 356 patients with PsA and 386 patients with SpA. In a prospective cohort setting, questionnaires regarding previous cardiovascular events and risk factors were used to assess cardiovascular risk and prevalence in patients with IA by calculating ORs using logistic regression models. RESULTS: 'Traditional' cardiovascular (CV) risk factors were significantly elevated in patients with IA compared with controls. Cardiovascular disease (CVD) ORs were increased in patients with RA and PsA compared with controls, 1.61 (95% CI: 1.04 to 2.48) and 2.12 (95% CI: 1.23 to 3.66), respectively, and a trend towards increased odds was observed in patients with SpA (OR 1.43; 95% CI: 0.79 to 2.59). After adjusting for traditional risk factors, CV risk was not increased in patients with RA (OR; 0.95, 95% CI: 0.58 to 1.55), PsA (OR 1.19; 95% CI: 0.64 to 2.22) and SpA (OR; 0.91, 95% CI: 0.47 to 1.77). CONCLUSION: CVD is currently still more prevalent in patients with IA compared with healthy controls and, more importantly, this elevated risk is highly influenced by an increased prevalence of 'traditional' CV risk factors. More attention to, as well as improvements in, identification and treatment of 'traditional' risk factors, need to be made for not only RA, but other IA conditions as well.

Gender-specific differences in patients with psoriatic arthritis receiving ustekinumab or tumour necrosis factor inhibitor: real-world data.

OBJECTIVE: Investigate effects of gender on disease characteristics and treatment impact in patients with PsA. METHODS: PsABio is a non-interventional European study in patients with PsA starting a biological DMARD [bDMARD; ustekinumab or TNF inhibitor (TNFi)]. This post-hoc analysis compared persistence, disease activity, patient-reported outcomes and safety between male and female patients at baseline and 6 and 12 months of treatment. RESULTS: At baseline, disease duration was 6.7 and 6.9 years for 512 females and 417 males respectively. Mean (95% CI) scores for females vs males were: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), 32.3 (30.3, 34.2) vs 26.8 (24.8, 28.9); HAQ-Disability Index (HAQ-DI), 1.3 (1.2, 1.4) vs 0.93 (0.86, 0.99); total PsA Impact of Disease-12 (PsAID-12) score, 6.0 (5.8, 6.2) vs 5.1 (4.9, 5.3), respectively. Improvements in scores were smaller in female than male patients. At 12 months, 175/303 (57.8%) female and 212/264 (80.3%) male patients achieved cDAPSA low disease activity, 96/285 (33.7%) and 137/247 (55.5%), achieved minimal disease activity (MDA), respectively. HAQ-DI scores were 0.85 (0.77, 0.92) vs 0.50 (0.43, 0.56), PsAID-12 scores 3.5 (3.3, 3.8) vs 2.4 (2.2, 2.6), respectively. Treatment persistence was lower in females than males (P ≤ 0.001). Lack of effectiveness was the predominant reason to stop, irrespective of gender and bDMARD. CONCLUSIONS: Before starting bDMARDs, females had more severe disease than males and a lower percentage reached favourable disease states, with lower persistence of treatment after 12 months. A better understanding of the mechanisms underlying these differences may improve therapeutic management in females with PsA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02627768.

18F-sodium fluoride PET-CT visualizes both axial and peripheral new bone formation in psoriatic arthritis patients.

PURPOSE: As bone formation is associated with psoriatic arthritis (PsA), positron emission tomography (PET) using a 18F-Fluoride tracer may enable sensitive detection of disease activity. Our primary aim was to determine the feasibility of whole-body 18F-sodium fluoride PET-CT in clinically active PsA patients to depict new bone formation (as a reflection of disease activity) at peripheral joints and entheses. Our secondary aim was to describe 18F-sodium fluoride findings in the axial skeleton. METHODS: Sixteen patients (female 10/16, age 50.6 ± 8.9 years) with PsA fulfilling CASPAR criteria or with a clinical diagnosis of PsA according to the treating rheumatologist and with ≥ 1 clinically active enthesitis site were included. Of each patient, a whole-body 18F-sodium fluoride PET-CT scan was performed. All scans were scored for PET-positive lesions at peripheral joints, enthesis sites and the spine. Clinical disease activity was assessed by swollen/tender joint count 44, enthesitis according to MASES and SPARCC scores. RESULTS: Out of 1088 evaluated joints, 109 joints showed PET enhancement, mainly in the interphalangeal and metatarsal joints of the feet (14/109, 12.9%) and the distal interphalangeal joints of the hands (14/109, 12.9%). PET positivity was found at 44/464 enthesis sites, mainly at the patella tendon insertion (11/44, 25%) and quadriceps tendon insertion (10/44, 22.7%). Of the PET-positive joints and enthesis sites, respectively 18.2% and 29.5% were clinically positive; 81.8% and 70.5% of the PET-positive joints and entheses respectively were clinically asymptomatic. In 11 patients, ≥ 1 axial PET-positive lesion was observed, mainly in the cervical spine. CONCLUSIONS: New molecular bone formation was observed on 18F-sodium fluoride PET-CT scans, in all domains in which PsA disease activity can be observed, with a substantial part showing no clinical symptoms. CLINICAL TRIAL REGISTRATION: EudraCT: 2017-004,850-40, registered on 13 December 2017.

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

OBJECTIVE: This literature review aimed to identify the most efficacious current interventions for dactylitis and provide up-to-date scientific evidence to support the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommendations on the management of psoriatic arthritis. METHODS: Original articles published from 2013 to 2020, registered in MEDLINE, Embase, and Cochrane Library, describing interventional trials and reporting dactylitis-related outcomes were included. The 20 members of the GRAPPA dactylitis group were divided into 9 subgroups according to treatment, and members of each group independently extracted data from articles/abstracts corresponding to their group by using a standardized data extraction form. RESULTS: Forty-nine publications were analyzed, representing 40 randomized clinical trials (RCTs) and including 16,752 patients. Dactylitis was assessed as a secondary outcome in 97.5% of these trials and more than 40% of RCTs did not employ a specific dactylitis measure or instrument. CONCLUSION: The emergence of agents with novel mechanisms of action in recent years, such as interleukin 17 (IL-17), IL-12/23, IL-23, and Janus kinase inhibitors, has significantly expanded the available treatment options for dactylitis. This article points out the lack of consensus regarding dactylitis assessment and the paucity of data concerning the effect of local steroid injections, nonsteroidal antiinflammatory drugs, and conventional disease-modifying antirheumatic drugs. Clinical trials evaluating the effect of these traditional and low-cost medications used to treat dactylitis should be encouraged.

Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis.

Interleukin (IL)-17 and tumor necrosis factor-alpha (TNF)-α are key players in psoriatic arthritis (PsA) pathogenesis. While both cytokines can be therapeutically targeted with beneficial clinical outcome, it is unclear whether inhibiting one cytokine will affect the other at sites of inflammation. If both act independently, this might provide a rationale for dual or combined inhibition of both cytokines. Here, we evaluated the effect of TNF blockade in PsA patients on IL-17 levels in both skin and synovial tissue biopsies. PsA patients with mild psoriatic skin lesions were randomized to receive either adalimumab or placebo for four weeks. Synovial and skin biopsies were obtained at weeks zero and four. Skin from healthy donors (HDs) was used for comparison. Expression of IL-17A, IL-17F, IL-17RA and IL-17RC was assessed by immunohistochemistry and analyzed with digital image analysis. We found relatively low levels of IL-17 and its receptors in the skin of PsA patients compared to HD, and only IL-17F in the dermis of lesional psoriatic skin was significantly higher compared to HD skin (p = 0.0002). Histologically IL-17A, IL-17F, IL-17RA and IL-17RC in skin and synovial tissue were not downregulated by adalimumab treatment. Thus, in this cohort of PsA patients with mild psoriasis, TNF blockade did not affect the protein levels of IL-17 cytokines and its receptors in skin and synovium, despite reduced cellular inflammation and improved clinical outcome for joint involvement.

Sustained remission with methotrexate monotherapy after 22-week induction treatment with TNF-alpha inhibitor and methotrexate in early psoriatic arthritis: an open-label extension of a randomized placebo-controlled trial.

BACKGROUND: If TNF inhibitors are initiated in the early stages of psoriatic arthritis, this could potentially modulate disease and therefore allow us to discontinue the TNF inhibitor after achieving remission. OBJECTIVE: To investigate whether remission induced by tumour necrosis factor alpha inhibitor (TNFi) and methotrexate in patients with early psoriatic arthritis is sustained after withdrawal of TNFi. METHODS: Open-label extension of a recently published double-blind, randomized placebo-controlled trial. Patients with psoriatic arthritis fulfilling the CASPAR criteria and with active disease at baseline (swollen and tender joint count ≥ 3) were randomized to either golimumab and methotrexate or matched placebo and methotrexate. Patients in Disease Activity Score (DAS) remission at week 22 continued in the open-label extension on methotrexate monotherapy. The primary end point was the percentage of patients in DAS-CRP remission (DAS < 1.6) at week 50. RESULTS: Eight patients from the original placebo group and 18 patients from the original TNFi group continued in the extension phase. At week 50, 6 out of 8 (75%) patients from the original MTX (methotrexate) group versus 10 out of 18 (56%) patients from the original MTX+TNFi group were in DAS-CRP remission (p = 0.347). Considering the total study population, 6 out of 24 (25%) of the original MTX group versus 10 out of 26 (38.5%) of the original MTX+TNFi group were in DAS remission at week 50 (p = 0.308). CONCLUSIONS: Remission achieved by initial combination treatment with TNFi and methotrexate in early psoriatic arthritis is maintained on methotrexate monotherapy in approximately half of the patients. TRIAL REGISTRATION: Registered at Clinicaltrials.gov with number NCT01871649 on June 7, 2013.