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• W4313477229 abstract "Psoriatic arthritis (PsA) is a chronic inflammatory arthritis and belongs to the family of spondyloarthropathies (SpA).1 Within the family of SpA, PsA is a distinct subgroup that has diverse clinical manifestations, including peripheral arthritis, enthesitis, dactylitis, and axial involvement, in addition to skin and nail psoriasis.1 Currently, the ClASsification of Psoriatic Arthritis (CASPAR) is the commonest classification used in randomized controlled trials. The CASPAR criteria have improved sensitivity in classifying PsA compared with previous classification criteria, allowing patients without skin psoriasis to be classified with the presence of family history of psoriasis, dactylitis, specific radiographic features, or absence of rheumatoid factor.2 This classification provides a mean to identify a homogeneous group of patients with PsA, distinct from other forms of SpA, reactive arthritis, or rheumatoid arthritis (RA) to enter into clinical trials, such that the effect of treatments can be properly interpreted. Although classification criteria may provide insights into diagnosis, clinical diagnosis is still a complex cognitive process made by an experienced clinician considering clinical manifestations, and biochemical and imaging features.3 The principle of management of PsA emphasizes “early diagnosis”, “early effective treatment”, and “treat-to-target” strategy.4 Conceptualized with the experience of RA, early treatment of inflammation reduces subsequent radiographic joint damage and hence long-term disability.5 A treat-to-target strategy has successfully reduced disability in patients with RA in the last two decades.6 For the case of PsA, there are several reasons to adopt a similar strategy in its management. First, erosions or irreversible joint damage occur early in PsA. In a prospective study, 27% of the patients had radiographic erosions on average 10 months after the onset of symptoms, and 47% of the patients have developed at least one erosion at the end of 2 years.7 Second, it has been well-described that a delay in diagnosis and appropriate treatment of PsA is associated with poorer outcomes, including joint erosions, radiographic joint damage, arthritis mutilans, sacroiliitis, and a lower chance of having drug-free remission.8 Third, a treat-to-target strategy has been shown to be feasible in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) study that targeted Minimal Disease Activity (MDA) as the treatment strategy.9 Lastly, it has been shown in multiple trials that patients achieving remission have less radiographic progression10, 11 and better cardiovascular outcomes.12 Advances in the understanding of the immune pathways has led to the discovery that autoimmune diseases depend on communication networks of cytokines that collapse upon neutralization of functionally vulnerable nodes. Tumor necrosis factor-α (TNF-α) seems to be the common node of the pathogenesis pathway for various inflammatory arthritis. Whilist the SpA spectrum of diseases is mediated by interleukin-17 (IL-17) pathways, in contrast to RA, which is mediated by IL-6 pathways.13 Apart from blocking TNF-α, blockage of IL-17 pathways has specifically demonstrated great improvement in outcomes for SpA.13 In addition, within SpA, we are beginning to see diverse efficacies of IL-23 versus IL-17 blockage. For example, IL-23 inhibition has a better response in patients with PsA, ulcerative colitis, and Crohn's disease, but is not effective for axial SpA where only IL-17 inhibition is relevant.13 Therefore, within PsA with diverse clinical manifestations, it is sensible to consider the types of biologics based on the predominant domains affected for the individual patient.14 The latest treatment recommendation guideline updates developed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in 2021 have reviewed the evidence of different classes of therapeutic options according to the predominant domains.15 For peripheral arthritis, conventional synthetic disease-modifying anti-inflammatory drugs, phosphodiesterase 4 inhibitor, biological disease-modifying anti-rheumatic drugs (DMARDs) (including TNF, IL-17, and IL-23 inhibitors), and Janus kinase inhibitor were strongly recommended with equal weights.15 For the axial domain, TNF and IL-17 inhibitors were both strongly recommended.15 Despite the low quality of evidence to support the use of conventional synthetic DMARDs for peripheral arthritis, it is still strongly recommended because of the reasonable response seen in observational studies,16-19 good experience of use, and universal accessibility.20 We now have a high level of evidence supporting TNF inhibitors as superior to methotrexate as a first-line therapy for patients with active peripheral diseases, particularly for those with early stage PsA.17-19 Very importantly, a treat-to-target strategy, consideration of patients' comorbidities, and shared decision-making are the overarching principles of management. Regardless of which drug is chosen as an initial therapy, regular and comprehensive reassessment of the patients and an escalation of therapeutic options should be considered if patients are not achieving the remission target. Despite advances in therapeutic options, 30%-40% of patients do not have an adequate response to any class of drugs, which constitutes a huge unmet need. Apart from the need for new drug development, biomarkers that have the potential for individual drug treatment should be able to give further guidance for treatment. A proof-of-concept study has shown that a stratified treatment regimen based on T-cell patterns stratified by flow cytometry was associated with doubling of clinical response compared with the standard biological DMARDs regimen.21 Although further research is required to validate the result, this offers the hope that relevant biomarkers that predict treatment outcomes would be expected. In conclusion, therapeutic advances in rheumatology have brought an evolutionary treatment paradigm. Several recommendation guidelines have been developed and updated to provide guidance to treat different clinical phenotypes of PsA.15, 22, 23 A domain-based evaluation of treatment options based on PsA manifestations is guided by evidence.15 Shared decision-making between physicians and patients, considering predominant domain manifestations and patient comorbidities, is recommended. In addition, a regular comprehensive assessment of treatment response and a treat-to-target strategy is advocated that should bring the best outcomes for patients with PsA. All authors (PEK, YHL, KSKM, AK, and YYL) provided their ideas and critical contributions. PEK, YHL, KSKM, AK, and YYL contributed to the editing of the manuscript. None declared. YYL is supported by the National Medical Research Council, Singapore (NMRC/CSA-Inv/0022/2017) and has received honoraria from AbbVie, DKSH, Janssen, Pfizer, and Novartis. YYL is an Editorial Board member of the journal and co-author of this article. They were excluded from the peer-review process and from all editorial decisions related to the acceptance and publication of this article. Peer-review was handled independently by members of the Editorial Board to minimize bias." @default.
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• W4313477229 title "Current treatment strategies and recommendations in psoriatic arthritis" @default.
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