Review ArticleUpdated therapies for the management of Psoriatic Arthritis
Introduction
Psoriatic arthritis (PsA) is a chronic inflammatory condition that affects the joints and periarticular structures, as well as the skin and nails. Its prevalence ranges from 0.06% to 0.25% in western countries (e.g. United States) [1]. Although PsA occasionally can precede psoriasis, approximately one third of patients with psoriasis may develop PsA [1].
PsA disease is progressive and closely associated with several comorbidities. Favorable long-term outcomes can be optimized with an early diagnosis, though its heterogeneous presentation can make diagnosis and management challenging for providers. Prompt treatment initiation is essential in improving prognosis and preventing further joint damage. Additionally, diagnosis can be indicative to providers of significant comorbidities requiring screening, including increased cardiovascular disease. Several screening tools have been developed to identify patients at risk for PsA, including the Toronto Psoriatic Arthritis Screening Questionnaire (TOPAS), the Psoriasis Epidemiology Screening Tool (PEST), the Psoriatic Arthritis Screening and Evaluation (PASE), and the Psoriasis and Arthritis Screening Questionnaire (PASQ) [2]. Of these, the TOPAS has the highest specificity, while the PEST has the highest sensitivity.
Outcome measures, such as the American College of Rheumatology Responder Index (ACR20), the Disease Activity Score for 28 joints (DAS28), the Minimal Disease Activity (MDA), the Disease Activity for Psoriatic Arthritis (DAPSA); the Psoriatic Arthritis Joint Activity Index (PsAJAI); the Composite Psoriatic Disease Activity Index (CPDAI), the Psoriasis Area and Severity Index (PASI); and indices for enthesitis and dactylitis currently are now in use to assess disease severity [2]. Using these measures to quantify treatment efficacy, therapy recommendations have been outlined by The Group for Research and Assessment of Psoriatic Arthritis (GRAPPA), the European League Against Rheumatism (EULAR), and more recently, the American Academy of Rheumatology (ACR)/National Psoriasis Foundation (NPF) [1,3].
PsA treatment options are diverse, including the traditional therapies of nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, conventional systemic disease-modifying antirheumatic drugs (csDMARDs), and the newest advent of biologics [1]. Despite the variety of drugs available for PsA, the landscape continues to broaden with more targeted and effective medications. Herein, we will review currently available therapies and discuss emerging agents and the mechanisms behind their efficacy.
Section snippets
Overview of treatment guidelines
The GRAPPA, EULAR, and ACR/NPF guidelines provide PsA-specific composite disease measures. Initially established in 2009, the GRAPPA guidelines are based on a review of six clinical domains (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) [4]. Recommendations were originally stratified by disease severity (mild, moderate, severe); this was removed in the 2015 updated guidelines, which organized treatment recommendations by available supporting evidence [4]. In
Comorbidities
Psoriasis and PsA are known to be accompanied by numerous comorbidities, including cardiovascular disease, diabetes, obesity, metabolic syndrome, osteoporosis, inflammatory bowel disease, and malignancies, among others [6]. Accordingly, effective management of PsA should incorporate a multidisciplinary approach. Consultations with appropriate subspecialties, including but not limited to endocrinology and cardiology, should be strongly considered in at-risk patients. Addressing management of
Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) are a commonly used initial therapeutic agent for PsA, particularly in those with minor joint involvement. However, previous studies have demonstrated their limited ability to modify or reduce disease progression. A four week clinical trial comparing nimesulide, a COX-2 selective NSAID, versus placebo in 76 patients revealed a significant decrease in tender and swollen joint count with 200 mg and 400 mg daily nimesulide dosing, not seen in the
Anti-TNF agents
Biologics have revolutionized targeted immunotherapy in psoriasis and PsA. The ability to selectively target inflammatory cytokines has improved our understanding of the pathophysiology of the disease. Specifically, TNF inhibitors have drastically improved the management of PsA, as they are effective in inhibiting radiographic disease progression [30]. Used in both psoriasis and PsA, TNF antagonists continue to be the therapy demonstrating the highest efficacy in treating PsA, on par with many
PDE4 inhibitors
Phosphodiesterases (PDEs) are composed of 11 families that serve to degrade cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP), which are second messengers regulating cellular function and metabolism [60]. PDE inhibitors act to increase cAMP levels and therefore modulate inflammatory cellular responses [47]. Patients with inflammatory diseases have been found to have higher quantities of PDE4 than healthy controls. In the skin, PDE4 is expressed in keratinocytes, neutrophils, and
Janus kinase (JAK) inhibitors
The JAK/STAT pathway mediates cytokine signaling in PsA, particularly within the IL-12, IL-23 and IL-17 axis, and may mediate the expansion of Th17 cells [[62], [63], [64]]. Tofacitinib is the first JAK inhibitor to be approved for the treatment of PsA. A phase III trial demonstrated that tofacitinib at doses of 5 mg or 10 mg twice daily in patients with psoriatic arthritis with possible prior DMARD use can improve clinical burden of disease, in several areas such as reduction of arthritis,
Co-stimulatory Blockade (Abatacept)
T cell activation requires interaction between the major histocompatibility complex (MHC) and the T cell receptor (TCR), as well as a second interaction between receptor/ligand pairs. One example of a second interaction is between antigen presenting cells (APCs) and CD28 on T cells [66]. This interaction is blocked by co-stimulatory blockade agents, thereby preventing T cell activation and ensuing damage.
The most well-known co-stimulatory blockade agents are abatacept [67]. Abatacept mimics
Drugs in preclinical development
An array of novel molecules targeting the inflammatory-proliferative mechanisms of psoriatic disease are in progress. A broad discussion is not within the scope of this review. Here, we will briefly discuss a few.
Concept of total care
Treatment for PsA remains incomplete without addressing comorbidities. Psoriatic disease is a multisystem disorder; there is an increased prevalence of metabolic syndrome in PsA (40%–60%), putting PsA patients at high cardiovascular risk [84,85]. Understandably, it is not possible to provide the full spectrum of healthcare during a brief rheumatology office visit. Thus, a multidisciplinary approach involving subspecialists should be employed. These can include dermatologists, cardiologists,
Conclusion
In conclusion, PsA is a chronic inflammatory condition of the skin and joints that is associated with debilitating comorbidities. Clinicians can consider the GRAPPA, EULAR, and ACR/NPF guidelines to create personalized treatment regimens for patients. Early diagnosis can be achieved with the use of screening tools and a multidisciplinary approach can reduce disease-associated morbidity. Successful management should aim to provide a comprehensive program as outlined as a “total care program” for
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