Psoriatic arthritis

Psoriatic arthritis occurs in 5 - 42% of patients with psoriasis. It is an inflammatory arthritis distinct from rheumatoid, being usually sero-negative, asymmetrical and often affecting the spine, sacro-iliac and distal interphalangeal joints. It runs a very variable course, from a mild non-destructive disease to a severe rapidly progressive erosive arthropathy, producing an 'arthritis mutilans' with a combination of bone lysis and joint ankylosis. Its pathogenesis is not as well understood as rheumatoid arthritis, but is thought to be similarly immune driven, with a qualitatively similar immunomodulatory cascade and cytokine profile. Quantitatively, however, there are distinct differences in cell ratios and cytokine levels that may well impact on therapeutic strategies. Current therapies, such as methotrexate and sulphasalazine, have yet to be shown to be significantly more effective than placebo in delaying damage and produce only marginal improvements in symptoms. The newer specific biological agents, such as the anticytokine antibodies, interleukins and more specific anti-T-cell therapies, are starting to be studied in psoriatic arthritis. The rationale for their use comes mostly from extrapolation of their efficacy in rheumatoid arthritis. It has yet to be seen whether they will be efficacious in treating the osteolysis, fibrosis and new bone formation particular to psoriatic arthritis. Any treatment for the arthritis must also help the skin. Greater understanding of psoriatic arthritis, its pathogenesis and natural history is required if we are to target these exciting but expensive therapies effectively.     

Psoriatic arthritis

Psoriatic arthritis occurs in 5 - 42% of patients with psoriasis. It is an inflammatory arthritis distinct from rheumatoid, being usually sero-negative, asymmetrical and often affecting the spine, sacro-iliac and distal interphalangeal joints. It runs a very variable course, from a mild non-destructive disease to a severe rapidly progressive erosive arthropathy, producing an ‘arthritis mutilans’ with a combination of bone lysis and joint ankylosis. Its pathogenesis is not as well understood as rheumatoid arthritis, but is thought to be similarly immune driven, with a qualitatively similar immunomodulatory cascade and cytokine profile. Quantitatively, however, there are distinct differences in cell ratios and cytokine levels that may well impact on therapeutic strategies. Current therapies, such as methotrexate and sulphasalazine, have yet to be shown to be significantly more effective than placebo in delaying damage and produce only marginal improvements in symptoms. The newer specific biological agents, such as the anticytokine antibodies, interleukins and more specific anti-T-cell therapies, are starting to be studied in psoriatic arthritis. The rationale for their use comes mostly from extrapolation of their efficacy in rheumatoid arthritis. It has yet to be seen whether they will be efficacious in treating the osteolysis, fibrosis and new bone formation particular to psoriatic arthritis. Any treatment for the arthritis must also help the skin. Greater understanding of psoriatic arthritis, its pathogenesis and natural history is required if we are to target these exciting but expensive therapies effectively.     

Psoriatic arthritis: current therapy and future directions

Introduction: Psoriatic arthritis (PsA) once regarded as an auto-inflammatory arthritis that involves the skin is proving to be more complex with a different driver of disease process compared to rheumatoid arthritis. As growing differences emerge between PsA and rheumatoid arthritis so have the experiences and responses to therapeutics used in both disease processes.

Areas covered: This review highlights articles of interest in the past 10 years in the OVID and PubMed database and focuses on major concepts regarding current disease-modifying anti-rheumatic drugs in PsA as well as newer target agents.

Expert opinion: Presently, it is agreed upon that use of tumor necrosis factor inhibitors (TNFi) has greatly changed our ability to manage varying aspects of disease in PsA. However, there remain many unanswered questions in which research in PsA is mirroring RA work, these include: i) the need for outcome measures that are more specific to PsA, ii) the concept of early and treat to target, iii) the role of highly sensitive imaging, and iv) efficacy of combination therapy and further targets in those unable to tolerate or fail TNFi.     

Psoriatic arthritis: advances in pharmacotherapy based on molecular target

The progress on the improved understanding of disease pathogenesis and molecular biology has changed the understanding of disease profiles, emphasizing aspects that simple clinical observation could not identify, and demarcating differences between clinical pictures that seemed to overlap. An example of this spectacular evolution is represented by psoriatic arthritis (PsA). This increase of knowledge on pathogenesis has led to an important impact on therapeutic approach. Therapies are now taken into account because their precise target is known. The authors describe treatment guidelines and revisit traditional therapies as well as innovative therapies in PsA.     

Methotrexate: new indication. Psoriatic arthritis: approved at last

Efficacy is mainly based on long experience but must be weighed against potentially severe adverse effects.     

An update on methotrexate pharmacogenetics in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that mainly affects the joints. When left untreated, the disease can result in irreversible joint damage with high morbidity and mortality. Disease-modifying antirheumatic drugs are the cornerstones of treatment in RA. Disease-modifying antirheumatic drugs not only ameliorate the clinical signs and symptoms of disease, but also prevent the radiographic progression of joint damage. Methotrexate is one such disease-modifying antirheumatic drug that has been used in the treatment of RA for over two decades with excellent long-term efficacy and safety. However, there is significant variability in patients' response to methotrexate, both in terms of efficacy and toxicity. At the present time, there are no reliable means of predicting, a priori, an individual patient's response to methotrexate. In this review, recent published literature on the pharmacogenetics of methotrexate in RA is highlighted. Pharmacogenetics may be a powerful tool for optimizing methotrexate therapy in patients with RA.     

Infliximab: new indication. Psoriatic arthritis: just another intravenous me-too drug

Minimal assessment, based on a non comparative prospective cohort study of single-agent therapy.     

IL-1F10基因多态性与类风湿关节炎遗传易感性研究

目的探讨类风湿关节炎易感性与白细胞介素-1F10（IL-1FIO）基因中rs6743376和rs6761276位点基因多态性的关系。方法采用病例对照的研究方法,收集安徽医科大学第一附属医院风湿科门诊确诊的类风湿关节炎患者184人和同期正常健康体检人群184人,采用高温连接酶的连接酶检测反应（LDR）方法检测两位点的单核苷酸多态性,分析基因型及等位基因频率在两组中的分布。结果白细胞介素-1FIO（IL-1FIO）基因中rs6743376和rs6761276位点基因型频率和等位基因频率在病例组和对照组中的分布差异无统计学意义,rs6743376位点基因型频率（x2=2．04,P=0．361）,等位基因频率（X2=0．187,P=0．667）;rs6761276位点基因型频率（X2．28,P=0．320）,等位基因频率（X2=0．206,P=0．650）。结论中国安徽省汉族类风湿关节炎患者遗传易感性与白细胞介素-1F10基因中rs6743376和rs6761276位点无关。     

Potential role of pharmacogenetics in anti-TNF treatment of rheumatoid arthritis and Crohn's disease

Etanercept, infliximab and adalimumab have shown clinical benefit in immune-mediated inflammatory diseases; however, the outcome of treatment with these tumour-necrosis factor inhibitors remains insufficient in approximately 40-60% and approximately 25-40% of individuals with rheumatoid arthritis and Crohn's disease, respectively. Moreover, their use is accompanied by adverse events and unintentional immune suppression. Pharmacogenetics has the potential to increase efficacy and ameliorate adverse events and immune suppression, and its application might be of clinical benefit for patients with rheumatoid arthritis and Crohn's disease. Pharmacogenetic studies have shown associations between single nucleotide polymorphisms in genes encoding enzymes related to the pharmacodynamics of these drugs and treatment outcome. As we discuss here, replication and prospective validation are warranted before pharmacogenetics can be used in clinical practice.     

Meta-analysis: tumour invasion-related genetic polymorphisms and gastric cancer susceptibility

Background  Host genetic susceptibility has been suggested as one of the most important possible explanations for interindividual difference in gastric cancer (GC) risk.
Aim  To evaluate the impact of tumour invasion-related gene polymorphisms, which may be involved in a variety of processes during GC development, such as cell adhesion and angiogenesis, on the risk of GC.
Methods  We reviewed published studies on tumour invasion-related gene polymorphisms and GC susceptibility until 31 March 2008, and then quantitatively summarized associations of the most widely-studied polymorphism, CDH1 −160C>A, with GC using meta-analysis.
Results  Twenty-seven eligible studies were included in this review. Fourteen polymorphisms significantly related to GC in at least one study were identified. For several polymorphisms, heterogeneous results were observed and associations in opposite directions were seen among Asian and Caucasian populations. In meta-analysis, CDH1 −160C>A showed an inverse association with GC among Asians (OR, 0.76; 95% CI, 0.55–1.05) and a positive association among Caucasians (OR, 1.40; 95% CI, 0.95–2.04).
Conclusions  This review suggests that genetic polymorphisms in tumour invasion could be candidate biomarkers of GC risk. However, differences between populations and stages of cancer need to be taken into account and may explain some of the inconsistencies found in previous studies.     

Sarcomas and pharmacogenetics

Sarcomas are a heterogeneous group of tumors, requiring different chemotherapeutic approaches. Recently, several regimens for metastatic tumors were evaluated with respect to the different responses to conventional chemotherapy of the various histologic subtypes of sarcomas. The impact of pharmacogenetics in the progress of chemotherapy appears to be crucial in defining the clinical response to many drugs, such as anthracycline or alkylating agents, that are widely used in treatment regimens for soft tissue sarcomas (STS) or sarcomas of the bone. Polymorphisms of metabolizing enzymes (e.g., cytochrome P450 and glutathione-S-transferase), transporter proteins (reduced folate carrier and P-glycoprotein) or target proteins (thymidylate synthase, methylenetetrahydrofolate reductase, dihydrofolate reductase, and c-KIT) may be responsible for an altered clinical outcome, in terms of both response and toxicity. The administration of new chemotherapeutic agents, such as imatinib for gastrointestinal tumors (GIST), requires the study of genetic polymorphisms possibly affecting the integrity of the target (c-KIT), which may provide valid information regarding possible developments of therapy. For STS and sarcoma of the bone, the genetic markers, which could be unambiguously predictive of the phenotypic profile of patients, are as yet undetermined.     

Clopidogrel pharmacogenetics: metabolism and drug interactions

The thienopyridine, clopidogrel bisulfate (clopidogrel), is the most widely prescribed antiplatelet therapy in the world. Clopidogrel, alone or in conjunction with aspirin as part of a dual antiplatelet therapy regimen, is the standard of care for reducing ischemic events in patients with acute coronary syndrome, recent myocardial infarction, recent stroke, or established peripheral artery disease. Initially approved for use in 1997, the label was updated by both the USA Food and Drug Administration and the European Medicines Agency in 2009 to include information regarding cytochrome P450 (CYP) genotype status and concomitant proton pump inhibitor use. Labeling warns of reduced effectiveness in those with impaired CYP2C19 function and to avoid concomitant clopidogrel use with drugs that are strong or moderate CYP2C19 inhibitors, such as omeprazole. The interpretation of this warning and the implementation in clinical practice is not without controversy. The following review provides a summary of the published evidence regarding CYP2C19 function, both genotype status and drug inhibition from concomitant proton pump inhibitors use, and response to clopidogrel.     

BSG基因多态性与中国汉族人群类风湿性关节炎的遗传易感性研究

目的：探讨BSG（Basigin）基因多态性与中国汉族人群类风湿性关节炎发病之间的相关性。方法：收集196例类风湿性关节炎患者和249例健康人群,应用PCR-RFLP的分析方法,对BSG基因T-10292A多态性进行基因分型,用ELISA法检测血清中可溶性CD147（sCD147）的表达。结果：病例组与对照组BSG基因T-10292A多态基因型的分布差异存在着统计学意义（P〈0．05）。与正常对照组相比,类风湿性关节炎患者血清中sCD147的浓度显著升高。与其他基因型患者相比,TT基因型患者,其sCD147的浓度最低。结论：BSG基因多态性与中国汉族人群类风湿性关节炎的发病可能相关。