Open prospective studies and randomized controlled trials (RCT) have shown the short-term efficacy of adalimumab (ADA) in psoriatic arthritis (PsA) and psoriasis. ADA effectively treated all varied musculoskeletal manife...Open prospective studies and randomized controlled trials (RCT) have shown the short-term efficacy of adalimumab (ADA) in psoriatic arthritis (PsA) and psoriasis. ADA effectively treated all varied musculoskeletal manifestations characteristic of PsA, including peripheral arthritis, spinal disease, enthesitis, and dactylitis. ADA significantly inhibited structural changes on radiographs, lessened disability, and improved quality of life in patients with active PsA. One study showed the efficacy of 24-week ADA therapy on bone marrow edema and erosions, as measured by magnetic resonance imaging. The clinical and radiographic efficacy of ADA demonstrated during short-term treatment was sustained during longterm treatment. ADA was generally well tolerated and its safety profile was similar to that reported in studies of ADA in rheumatoid arthritis. Overall, ADA has a favorable risk-benefit profile in PsA. The combination of ADA and cyclosporine seems to be more effective than ADA monotherapy in patients with active PsA and inadequate response to methotrexate; however, this observation must be confirmed in RCT.
In this update on etanercept (ETN) in psoriatic arthritis (PsA) we analyze this drug's mechanism of action, clinical efficacy/effectiveness, optimal dosage, disease-modifying antirheumatic drugs (DMARD) association, radi...In this update on etanercept (ETN) in psoriatic arthritis (PsA) we analyze this drug's mechanism of action, clinical efficacy/effectiveness, optimal dosage, disease-modifying antirheumatic drugs (DMARD) association, radiological progression, safety, switching aspects, and pharmacoeconomy. The efficacy/effectiveness of ETN in PsA has been demonstrated in randomized placebo-controlled trials as well as in observational studies representing routine clinical practice. At 1 and 2 years, ETN inhibited radiographic disease progression, assessed by the modified total Sharp score. ETN (generally at a dosage of 50 mg/weekly) can be used either in monotherapy or in combination with DMARD such as methotrexate. A systematic search of randomized, placebo-controlled trials of ETN to treat adults with plaque psoriasis or PsA suggests that the short-term risk/benefit ratio is favorable. Longterm studies, such as observational studies, confirmed this safety profile of ETN. A variable percentage of patients withdrew anti-tumor necrosis factor-α (TNF-α) inhibitor treatment owing to inefficacy or poor tolerability. Observational studies showed that in the case of treatment failure with 1 agent, switching to the other agent may also be useful in patients with PsA because of the different molecular structures and targets of available TNF-α blockers. The clinical effect of ETN is associated with favorable pharmacoeconomic considerations.
Tumor necrosis factor-α (TNF-α) plays a central role in the pathogenesis of psoriasis and psoriatic arthritis (PsA). Recently, 2 expert committees provided evidence-based recommendations for the treatment of PsA. Anti-TN...Tumor necrosis factor-α (TNF-α) plays a central role in the pathogenesis of psoriasis and psoriatic arthritis (PsA). Recently, 2 expert committees provided evidence-based recommendations for the treatment of PsA. Anti-TNF-α drugs are indicated in all forms of PsA resistant to traditional therapeutic approaches. Anti-TNF-α infliximab (IFX) is an immunoglobulin G-1 antibody that binds to soluble and cell membrane-bound TNF-α with its inactivation. Confirming previous open-label studies, 2 randomized, placebo-controlled clinical trials, IMPACT and IMPACT2, have provided evidence of the efficacy and safety of IFX in the treatment of PsA as evaluated by American College of Rheumatology (ACR)20, ACR50, and ACR70 response rates. At Week 16, a significant proportion of 51 IFX-treated patients achieved ACR20, ACR50, and ACR70 responses compared to the 51 patients of the placebo arm in the IMPACT trial. In the IMPACT2 study, 58% of the IFX-treated patients and 11% of placebo patients achieved an ACR20 response (p < 0.001), and 41% and 27% of patients in the IFX group were ACR50 and ACR70 responders, compared with 4% and 2% of placebo patients, respectively. Of note, a significant inhibition of radiographic disease progression was observed in the IFX-treated group. In both trials, psoriasis improvement was recorded in more than 80% of patients receiving IFX, with a significant difference compared to placebo group. IFX was well tolerated, with no difference compared to placebo in terms of adverse events. The extension phase of these studies showed the sustained efficacy and safety of the drug.
Although several reviews and metaanalyses have shown lack of evidence of efficacy of traditional disease-modifying antirheumatic drugs (DMARD) in psoriatic arthritis (PsA), these drugs are very often used and are recomme...Although several reviews and metaanalyses have shown lack of evidence of efficacy of traditional disease-modifying antirheumatic drugs (DMARD) in psoriatic arthritis (PsA), these drugs are very often used and are recommended by treatment guidelines around the world as first-line therapy for most patients with PsA. Some new investigations showed that higher doses of methotrexate (MTX) are more beneficial for patients with PsA with peripheral involvement. Also, observational studies have shown that retention of MTX for patients with PsA is comparable to that of patients with rheumatoid arthritis (RA), and that with MTX, remission is achievable by around 20% of patients with PsA. Sulfasalazine, leflunomide, and cyclosporine have also been shown to be effective in a small number of patients, although the overall effect on disease activity for these drugs is small. Although combination of anti-tumor necrosis factor agents with traditional DMARD is not mandatory in PsA as it is in RA, there is evidence that some extra benefit might be achieved when combinations are used, not only for the joints but for the skin. There is still room for the use of traditional DMARD in PsA, and for the time being, DMARD should still be considered as first-line therapy for most patients with PsA.
Patients with psoriatic arthritis (PsA) have a higher inflammatory burden and poorer quality of life compared to patients with psoriasis without PsA. Early identification of PsA may prevent joint damage progression and i...Patients with psoriatic arthritis (PsA) have a higher inflammatory burden and poorer quality of life compared to patients with psoriasis without PsA. Early identification of PsA may prevent joint damage progression and improve quality of life. Soluble biomarkers have the potential to be useful for screening patients with psoriasis for underlying PsA so that appropriate referral to a rheumatologist is made. Pilot studies have shown that C-reactive protein, interleukin 6, cartilage oligomeric matrix protein (COMP), Dickkopf-1, and macrophage-colony stimulating factor may differentiate PsA from psoriasis without PsA. Compared with controls, increased serum levels of receptor activator of nuclear factor-κB ligand, tumor necrosis factor superfamily member 14, matrix metalloproteinase-3 (MMP-3), and COMP are independently associated with psoriatic disease. Increased levels of high-sensitivity CRP (hsCRP), osteoprotegerin (OPG), MMP-3, and the ratio of C-propeptide of type II collagen (CPII) to collagen fragment neoepitopes Col2-3/4 C(long mono) (C2C) are independently associated with PsA. A combination of hsCRP, OPG, MMP-3, and the ratio CPII of C2C was able to distinguish patients with PsA from those with psoriasis alone in a receiver-operating characteristic curve analysis, with area under the curve 0.904. Therefore, a combination of the above biomarkers may at least have a role in screening patients with psoriasis for PsA. These findings need to be validated in prospective studies.
Fiocco U, Oliviero F, Sfriso P
… +16 more, Calabrese F, Lunardi F, Scagliori E, Rubaltelli L, Stramare R, Di Maggio A, Nardacchione R, Cozzi L, Molena B, Felicetti M, Gazzola K, Lo Nigro A, Accordi B, Roux-Lombard P, Dayer JM, Punzi L
OBJECTIVE: To find candidate biomarkers of psoriatic arthritis (PsA). A panel of synovial fluid (SF) and synovial tissue (ST) biomarkers was analyzed in patients with resistant peripheral PsA, in relation to clinical and...OBJECTIVE: To find candidate biomarkers of psoriatic arthritis (PsA). A panel of synovial fluid (SF) and synovial tissue (ST) biomarkers was analyzed in patients with resistant peripheral PsA, in relation to clinical and imaging outcomes of synovitis response following serial intraarticular (IA) etanercept injections (12.5 mg). METHODS: Fourteen PsA patients with resistant knee joint synovitis were treated with 4 IA etanercept injections in a single knee joint, once every 2 weeks. Primary outcome (Thompson's knee index: THOMP) and secondary outcomes were assessed at baseline and end of study: C-reactive protein, Knee Joint Articular Index (KJAI), Health Assessment Questionnaire disability index, maximal synovial thickness (MST) by gray-scale ultrasonography, contrast-enhanced magnetic resonance imaging (C+MRI), ST-cluster differentiation (CD)45+ mononuclear cell, ST-CD31+ vessels, and ST-CD105+ angiogenic endothelial cells, along with levels of SF interleukin 1ß (IL-1ß), IL-1 receptor antagonist (Ra), and IL-6. RESULTS: At the end of the study, clinical and imaging outcomes, ST and SF biological markers were significantly reduced compared to baseline. There was a significant association between IL-6 and either THOMP or KJAI; between either ST-CD31+ or ST-CD105+ or ST-CD45+; between ST and SF biomarkers expression (CD45+ and IL-1ß) and between ST-CD45+ and both KJAI and MRI-MST. Comparing pre- versus post-IA etanercept injection changes (Δ), Δ IL-1ß was significantly correlated with both Δ IL-6 and with Δ IL-1Ra and Δ IL-6 with Δ IL-1Ra. CONCLUSION: The association to disease activity and the changes following IA treatment indicate that ST-CD45+ and ST-CD31+, along with SF-IL-6 and SF-IL-1ß, may represent candidate biomarkers of the knee synovitis response to IA tumor necrosis factor-α blockade.
Biomarkers can provide insights into disease pathogenesis and assist clinicians in screening patients with psoriasis for arthritis. They can also help to stratify patients who are at risk for progression to bone destruct...Biomarkers can provide insights into disease pathogenesis and assist clinicians in screening patients with psoriasis for arthritis. They can also help to stratify patients who are at risk for progression to bone destruction or ankylosis. Biomarkers in psoriatic disease are still in the discovery phase, but the field is advancing at a rapid pace. This review discusses definitions of the different types of biomarkers and the development of markers that reflect preclinical and early psoriatic arthritis along with those that may be able to predict disease severity and response to anti-tumor necrosis factor agents.
This article summarizes the state of radiological assessment of axial involvement in psoriatic arthritis (PsA). The definition and measurement of axial disease in PsA remain problematic and this situation in turn could a...This article summarizes the state of radiological assessment of axial involvement in psoriatic arthritis (PsA). The definition and measurement of axial disease in PsA remain problematic and this situation in turn could affect the choice of approach to evaluate radiological findings of the spine. At present, the radiological assessment has been evaluated by using scoring systems borrowed from ankylosing spondylitis (AS). In particular, the Bath AS Radiology Index (BASRI) and the modified Stoke AS Spine Score (m-SASSS) have been validated for axial PsA. A recent study showed that BASRI and m-SASSS were valid instruments; however, neither score encompassed all radiological features of PsA. Therefore, a new index for assessing radiological axial involvement in PsA was developed--the PsA Spondylitis Radiology Index (PASRI). This new index encompassed a greater range of the spinal radiological features of PsA, providing a greater score range, and it correlated well with anthropometric and patient-reported outcomes. Recently, a study assessed the sensitivity to change of BASRI, m-SASSS, and PASRI, and showed that these 3 instruments provided a moderate sensitivity to change but high specificity to detect the true changes.
The evolution of dedicated magnetic resonance imaging (MRI) musculoskeletal equipment allows new sequences and better images of the nail unit. The use of MRI has modified the imaging strategies used in treating inflammat...The evolution of dedicated magnetic resonance imaging (MRI) musculoskeletal equipment allows new sequences and better images of the nail unit. The use of MRI has modified the imaging strategies used in treating inflammatory arthritis. In the case of psoriatic arthritis (PsA), the MRI study of the nail unit identifies nail involvement, which appears as an initial lesion for the induction of distal phalanx damage and consequently of distal interphalangeal joint arthritis. All patients with psoriasis, even in the absence of a clinically evident onychopathy, show characteristic MRI changes in the nail. This evidence could have a practical diagnostic value, because MRI study of the nail could document diagnosis in patients with undifferentiated spondyloarthropathies who have a barely evident psoriasis. We discuss the advantages and problems related to the use of low-field and high-field MRI in the study of the nail unit of patients with PsA.
OBJECTIVE: Dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous...OBJECTIVE: Dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous administration of contrast agent, evaluates synovitis and bone marrow edema in psoriatic arthritis (PsA). In this pilot study, we looked at possible differences between joint synovitis and tenosynovitis in PsA as compared with rheumatoid arthritis (RA). METHODS: Seven patients with PsA and 10 with RA were studied. After DCE-MRI was performed on 3 axial slices of the wrist, the enhancement ratio was calculated on 6 different regions of interest (ROI) of the synovial membrane outlined by the operator: the wrist compartment, 3 extensor tendon compartments, and 2 flexor compartments. DCE-MRI results were quantitatively analyzed using the Dynamika software, a computer-aided semiautomated method. RESULTS: In PsA, the area of the ROI outlined around the first and second extensor compartments was larger than in RA; the opposite was true for the extensor carpi ulnaris region. The volume of inflammation was significantly higher in RA than in PsA for all the extensor compartments except the second, and in the joint synovial membrane. The DCE-MRI indicators of the degree of inflammation were higher for PsA in the joint synovial membrane (p = 0.002 and p < 0.001, respectively). There was a significant correlation between volume of inflammation but not its degree and 28-joint Disease Activity Score at the level of the wrist joint (r = 0.6; p = 0.01). CONCLUSION: DCE-MRI can reveal useful and potentially clinically important information on the characteristics of different types of arthritis.
Ultrasound (US) is a rapidly evolving technique that is gaining increasing success in the assessment of psoriatic arthritis (PsA). It permits early detection and careful characterization of the inflammatory process at di...Ultrasound (US) is a rapidly evolving technique that is gaining increasing success in the assessment of psoriatic arthritis (PsA). It permits early detection and careful characterization of the inflammatory process at different tissues, which is important in diagnostic and therapeutic procedures. US presents several advantages over other imaging techniques: it is patient-friendly, safe, noninvasive, free of ionizing radiation, less expensive, and permits multiple target assessment in real time without the need for external referral. The aim of this report was to analyze the potential role of US in the assessment and management of PsA and to discuss the current evidence supporting its application in daily clinical practice.
Osteoporosis (OP) is a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture. The prevalence of OP in the general population is very high as established in several...Osteoporosis (OP) is a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture. The prevalence of OP in the general population is very high as established in several studies, and OP represents one of the possible aspects of bone involvement in arthritis. In psoriatic arthritis this involvement is particularly complex because it affects not only mechanisms of bone loss but also of bone formation. We will discuss these aspects and the available epidemiological data.
OBJECTIVE: To evaluate the mortality associated with psoriatic arthritis (PsA) and causes of death. METHODS: Data were evaluated from several published studies identified by a literature search. A standardized mortality...OBJECTIVE: To evaluate the mortality associated with psoriatic arthritis (PsA) and causes of death. METHODS: Data were evaluated from several published studies identified by a literature search. A standardized mortality ratio was documented when available, as were causes of death derived from clinical databases, death certificates, and mortality databases. In some studies, mortality data was stratified by sex, age, and calendar year with time trend analysis. RESULTS: There were variable reports of increased mortality in PsA that may be explained by factors such as pattern of referral, the severity of arthritis and/or skin psoriasis, and treatment exposure. There appears to be a greater incidence of cardiovascular death in psoriatic disease, although further studies are needed to separate the effect of skin psoriasis from arthritis. CONCLUSION: PsA is not a mild disease and mortality may be increased in more severe disease. Although cardiovascular risk is more substantiated in severe psoriasis than in arthritis, it would be remiss not to evaluate the cardiovascular risk profile in all patients with psoriatic disease. It is important to treat patients with PsA early and aggressively to prevent disease severity that may influence longevity.
OBJECTIVE: To compare the power Doppler ultrasonography (PDUS) pictures of peripheral entheses in patients with psoriatic arthritis (PsA) and fibromyalgia (FM). METHODS: Thirty patients with PsA and 30 with FM participat...OBJECTIVE: To compare the power Doppler ultrasonography (PDUS) pictures of peripheral entheses in patients with psoriatic arthritis (PsA) and fibromyalgia (FM). METHODS: Thirty patients with PsA and 30 with FM participating in a study aimed at identifying the clinical features that distinguish the 2 conditions underwent the PDUS assessment of 14 major peripheral entheses. All of the detected entheseal changes were recorded and scored, and the data were statistically analyzed by means of univariate analysis and receiver-operating characteristic curves. RESULTS: Four hundred twenty entheseal sites were assessed in each group of patients. At least 1 lesion was detected in each of the patients with PsA and in 80% of the patients with FM (p = 0.01), but inflammatory changes were present in respectively 70% and 23% (p = 0.001). A cutoff point of ≥ 3 involved sites had the greatest discriminating power in the patients with PsA, who were the only patients with bony erosions. PDUS signs of plantar fascia enthesopathy and Achilles tendon inflammation were highly specific of PsA. CONCLUSION: PDUS assessment of the peripheral entheses distinguishes patients with PsA and patients with FM in terms of the number and distribution of the involved sites, and the presence of inflammatory changes.
J Rheumatol Suppl
· 2012 Jul · PMID 22751586
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Psoriasis is a common Th-1 and Th-17-mediated chronic inflammatory disease that has been associated with metabolic syndrome, a constellation of cardiovascular risk factors including obesity, hypertension, dyslipidemia, a...Psoriasis is a common Th-1 and Th-17-mediated chronic inflammatory disease that has been associated with metabolic syndrome, a constellation of cardiovascular risk factors including obesity, hypertension, dyslipidemia, and insulin resistance. Overlapping inflammatory pathways and genetic susceptibility may be potential biologic links underlying this association. Multiple epidemiologic studies have consistently demonstrated higher prevalence of metabolic syndrome in patients with psoriasis. Dose-response relationships between more severe psoriasis and higher prevalence of metabolic syndrome components were recently established. This association has important clinical implications for the comprehensive management of psoriasis: Patients with psoriasis should be routinely screened for metabolic syndrome and treated accordingly to manage cardiometabolic risk, while clinicians should monitor potential effects on treatment efficacy and safety in patients with comorbid psoriasis and metabolic syndrome. Further research will be necessary to establish the directionality of this association and to explore the effect of treatment on these comorbid diseases.
Since the 1970s, asymptomatic involvement of several musculoskeletal structures was described in patients with psoriatic arthritis (PsA). We recently designated this clinical condition as occult PsA. This concept address...Since the 1970s, asymptomatic involvement of several musculoskeletal structures was described in patients with psoriatic arthritis (PsA). We recently designated this clinical condition as occult PsA. This concept addresses an "underground" inflammatory process that can eventually cause structural damage. The percentage of PsA cases occurring in an occult manner remains to be determined but it does not seem small. From a teaching perspective, we suggest differentiating occult PsA into 3 subsets: real occult PsA, characterized by a continuous asymptomatic course; temporary occult PsA, in which the clinical course remains asymptomatic for a period; and limited occult PsA, which occurs asymptomatically in some areas of the body but is clinically evident in others. Some serum biomarkers could identify patients to be studied with imaging techniques to discover real occult PsA. Since an asymptomatic course was also reported for other spondyloarthropathies, the concept of occult arthritis could be expanded to the whole field of such conditions.
Psoriatic arthritis (PsA) is a multifaceted disease that challenges outcome methodologists. A number of measures have been used to define remission in PsA but they have been mostly articular. Composite measures of diseas...Psoriatic arthritis (PsA) is a multifaceted disease that challenges outcome methodologists. A number of measures have been used to define remission in PsA but they have been mostly articular. Composite measures of disease activity and low disease states are now emerging, but further work is required to assess the implications of achieving these goals and to develop cost-effective treatment strategies to achieve them.
Psoriatic arthritis and spondyloarthritis (SpA) are complex immune-mediated diseases affecting peripheral and axial joints. T cells have been considered fundamental in triggering the disease and maintaining the process i...Psoriatic arthritis and spondyloarthritis (SpA) are complex immune-mediated diseases affecting peripheral and axial joints. T cells have been considered fundamental in triggering the disease and maintaining the process in the chronic phase. The recent discovery of the CD4+ Th17 lymphocyte subset and the interleukin 23/interleukin 17 axis has further contributed to the definition of unknown pathways, challenging previous models and the role of Th1/Th2 T cells in immune mediated diseases, including SpA.
Tendon, ligament, and capsular insertions are parts of "enthesis organs" whereby the enthesis itself has an elaborate functional integration with the adjacent soft tissues and the synovium in particular. The purpose of t...Tendon, ligament, and capsular insertions are parts of "enthesis organs" whereby the enthesis itself has an elaborate functional integration with the adjacent soft tissues and the synovium in particular. The purpose of this article is to review the sophisticated degree of integration between insertions and adjacent synovium in what has been dubbed "synovio-entheseal complexes" (SEC). SEC arise at multiple sites in the immediate vicinity of insertions and may also arise within the joint capsule at sites well away from enthesis insertions. Not only does this relationship between the enthesis and synovium hold in synovial joints, but it is also crucial for understanding the microanatomical basis for joint disease localization to tendons in the seronegative spondyloarthropathies as well as in other conditions including osteoarthritis. The fibrocartilages at insertions are prone to microdamage whereas this tissue is completely devoid of immune cells. In healthy conditions, the synovium lubricates and nourishes the entheseal associated fibrocartilages, but damage or aberrant tissue repair responses at the insertion may manifest as an immediately adjacent synovitis or tenosynovitis, given that the synovium has resident immune cell populations and the ability to undergo substantial hyperplasia. Therefore SEC are likely to represent key orchestrators that contribute to joint inflammation by mechanisms that have been hitherto poorly appreciated.
Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease with both autoimmune and autoinflammatory features. Evidence supports the distinct nature of PsA regarding its clinical, genetic, immunohistochemical,...Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease with both autoimmune and autoinflammatory features. Evidence supports the distinct nature of PsA regarding its clinical, genetic, immunohistochemical, and imaging features. Such features can help to distinguish PsA from other common rheumatic diseases. Apart from peripheral joint involvement, the musculoskeletal lesions in PsA include enthesitis and involvement of the distal interphalangeal joint (frequently associated with nail involvement, dactylitis, and axial involvement). The traditional model of pathogenesis in PsA has identified it as an autoimmune disease; however, an alternative model classifies it as having autoinflammatory features. Similarly, there are important new genetic observations focusing on the HLA region, and genome-wide association that confirms the genetic heterogeneity of patients with psoriasis and patients with PsA. Newer imaging techniques have also provided a much more detailed characterization of tissue abnormalities, in particular highlighting the extent of new bone formation, which is quite distinct from rheumatoid arthritis.