银屑病关节炎的药物治疗

银屑病关节炎是一种与银屑病相关的炎症性关节病变,临床表现轻重不一、病情迁延反复,可呈轻微非毁损性单关节炎、也可能发展迅速而出现毁损性多关节炎并出现骨溶解和关节强直.银屑病关节炎的发病机制未明,其治疗长期困扰着风湿科及皮肤科医生.本文就银屑病关节炎的药物治疗进行综述.     

银屑病关节炎的药物治疗

银屑病关节炎是一种与银屑病相关的炎症性关节病变,临床表现轻重不一、病情迁延反复,可呈轻微非毁损性单关节炎、也可能发展迅速而出现毁损性多关节炎并出现骨溶解和关节强直。银屑病关节炎的发病机制未明,其治疗长期困扰着风湿科及皮肤科医生。本文就银屑病关节炎的药物治疗进行综述。     

Apremilast for the treatment of psoriatic arthritis

Psoriatic arthritis occurs in about one-third of patients with psoriasis, and is a severely disabling, progressive inflammatory spondyloarthropathy typically treated with non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, TNF-α inhibitors and ustekinumab. These medications moderately improve the arthritis, dactylitis, and enthesitis that characterize psoriatic arthritis, however, they are associated with serious long-term adverse effects, issues with safety and tolerability, and high cost. Moreover, many patients do not respond or have resistant or recurrent manifestations to these agents. Apremilast is an orally available phosphodiesterase type 4 inhibitor that may block the pathogenic inflammatory Th17 and Th1 pathways upstream of current biologics, which target extracellular molecules of the immunological response.     

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: 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.     

Juvenile idiopathic arthritis: current and future treatment options

Juvenile idiopathic arthritis is the most common rheumatic disease in children. The management of juvenile idiopathic arthritis has improved in recent decades, and morbidity due to the disease is significantly decreased. In particular, the use of more effective drugs and their combination has changed the course of the disease in many patients. The increasing knowledge of inflammation mechanisms has lead to the development of new agents that target specific cytokines interfering with the inflammatory cascade. In particular, anti-TNF agents seem effective: etanercept is the only one licensed for juvenile idiopathic arthritis, and Phase III trials on two other anti-TNF agents, infliximab and adalimumab, are ongoing. This review discusses the current practice in the medical management of juvenile idiopathic arthritis, and potential new agents are discussed.     

Key findings from studies of methotrexate tapering and withdrawal in rheumatoid arthritis

Methotrexate is the dominant initial drug in the management of rheumatoid arthritis (RA). Despite its widespread use, methotrexate is associated with a number of adverse effects. Tapering its dose to the minimal amount required to maintain RA remission is, therefore, an important clinical goal. While the complete withdrawal of disease-modifying anti-rheumatic drugs is associated with a definite risk of a disease flare, it is unclear as to what the risk is specific to methotrexate withdrawal and whether this can be minimized by gradual dose reduction (termed ‘tapering’). This review examines studies of methotrexate tapering and withdrawal on RA outcomes. It covers three scenarios: tapering/withdrawing methotrexate monotherapy; tapering/withdrawing methotrexate as part of a ‘step-down’ combination disease-modifying anti-rheumatic drug regimen; and tapering/withdrawing methotrexate when it is being co-prescribed with biologic agents.     

Approaches to the treatment of early rheumatoid arthritis with disease-modifying antirheumatic drugs

This paper reviews recent approaches to treatment of early rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs (DMARDs). The literature on treatment the early RA published between 1995 and 2007 was accessed through the PubMed database from the National Library of Medicine. Keywords were 'early rheumatoid arthritis', 'disease-modifying antirheumatic drugs', 'biologic agents' and 'combination therapy'. Only results of trials on human subjects that directly measured the effects of DMARDs or biological agents on clinical, laboratory parameters and radiological progression of early RA were selected. Combination therapy suppresses RA activity and radiological progression more effectively than monotherapy. If better control of RA is evident after 3–6 months of treatment with the combination of DMARDs, one must still decide whether to stop the first DMARD, stop the second, or continue with the combination. Combination therapy biological agents (infliximab, adalimumab) with methotrexate and etanercept therapy alone may induce remission in many patients with early RA. It is a method of choice in patients with an adverse prognosis. The main indications for combination therapy 'standard' DMARDs or combination 1 DMARDs with a biological agent are such variables as detection of a shared epitope, increase of concentration of anticyclic citrullinated peptide antibodies, rheumatoid factor, C-reactive protein, 28-joint disease activity score, Sharp score and presence of erosion in joints. The majority of rheumatologists believe that patients with RA should be treated with DMARDs earlier rather than later in the disease process. Further trials should establish the optimal approaches to early RA therapy.     

Emerging drugs for psoriatic arthritis

Importance of the field: The socioeconomic burden of psoriatic arthritis (PsA) is considerable and not different from that of rheumatoid arthritis. Current treatment options do not always allow reaching the therapeutic objectives consisting of the remission of symptoms and prevention of the appearance of damage in the early stage of PsA or the blocking of PsA progression in the established cases.

Areas covered in this review: After reviewing the current treatment choices, we examine the new drugs in clinical Phase II and III trials for PsA up to January 2010. Information was mainly obtained from the network of international clinical trial registries.

What the reader will gain: The current management of PsA includes NSAIDs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α blocking agents. These last drugs are more effective than traditional DMARDs on symptoms/signs of inflammation, quality of life and function and can inhibit the progression of the structural joint damage. Recent advancement in the knowledge of the immunopathogenesis of PsA has permitted the development of novel drugs including new TNF-α blockers, IL-1, -6, -12, -23 and -17 inhibitors, co-stimulator modulation inhibitors, B-cell depleting agents, small molecules and receptor activator of NF-κB/receptor activator of NF-κB ligand inhibitors.

Take home message: The currently available anti-TNF-α blocking agents have revolutionized the management of PsA. However, there is a need for more effective and safer drugs.     

Pharmacotherapy of scleritis: current paradigms and future directions

Introduction: Scleritis is an inflammatory condition affecting the eye wall that may be associated with a number of systemic inflammatory diseases. Because scleritis can be refractory to standard treatment, knowledge of the body of available and emerging therapies is paramount and is reviewed here.

Areas covered: This review focuses on both traditional and emerging therapies for noninfectious scleritis. The authors cover the mechanisms of action and potential adverse effects of each of the treatment modalities. In addition, a summary of the significant MEDLINE indexed literature under the subject heading ‘scleritis', ‘treatment', ‘immunomodulator' will be provided on each therapy, including commentary on appropriate use and relative contraindications. Novel treatments and potential drug candidates that are currently being evaluated in clinical trials with therapeutic potential will also be reviewed.

Expert opinion: While oral nonsteroidal anti-inflammatory drugs and oral corticosteroids are widely used, effective, first-line agents for inflammatory scleritis, refractory cases require antimetabolites, T-cell inhibitors, or biologic response modifiers. In particular, there is emerging evidence for the use of targeted biologic response modifiers, and potentially, for local drug delivery.     

Abatacept: the evidence for its place in the treatment of rheumatoid arthritis

Introduction:

Rheumatoid arthritis (RA) is the most common inflammatory joint disease in adults with a prevalence of 0.5–1%. The development of targeted therapies, especially anti-TNF (tumor necrosis factor) treatment, has improved disease outcome during the last decade. But despite this progress 25–30% of patients still show unsatisfactory response. Abatacept is a costimulation blocker that inhibits T-cell activation and interrupts the process that leads to inflammation in RA.

Aims:

The purpose of this article is to review the clinical trials of abatacept and to discuss how it will fit into the treatment of RA. The medical literature was reviewed for appropriate articles and 123 articles have been identified containing the search terms “abatacept OR CTLA4-Ig AND rheumatoid.” All clinical trials were reviewed with respect to clinical and radiologic outcome, quality of life, and safety of patients with RA receiving abatacept therapy.

Evidence review:

There are seven (phase II or phase III) clinical trials that have clearly demonstrated efficacy and safety of this new drug. Furthermore, radiographic data show that abatacept also inhibits the progression of joint destruction, one of the important burdens of RA. Abatacept can be used concomitantly with conventional disease-modifying antirheumatic drugs or as monotherapy. Due to an increased risk of infections and malignancies but without an important enhancement of efficacy, simultaneous treatment with abatacept and other biologic response modifiers is not recommended.

Place in therapy:

With its different mechanism of action, abatacept may be an alternative therapy for patients with an inadequate response to other arthritis therapies, especially for those patients with RA refractory to anti-TNF treatment. Cost effectiveness is dependent on underlying disease progression.     

Pharmacogenetics and pharmacogenomics in psoriasis treatment: current challenges and future prospects

Introduction: Topical, systemic, oral disease modifying, and biologic agents are part of the armamentarium to manage psoriatic disease. The choice of therapy depends upon disease severity, relevant co-morbidities and patient preference. There is great variability in patient response with these agents, and there is still no clear method of selecting the preferred therapeutic agent for efficacy or lack of adverse events.

Areas covered: This article will review the pharmacogenetic and pharmacogenomic targets that are currently known with respect to psoriasis vulgaris, and the most frequent co-morbidity of psoriasis, psoriatic arthritis.

Expert opinion: Presently, no clinically actionable biomarker exists for any therapeutic agent used to treat psoriasis or psoriatic arthritis. The lack of validated outcome measures and conflicting results of open-label studies conducted may be attributed to a multitude of issues that confound discovery. Consequently, studies have been underpowered to identify genes or genetic variants worth translating to clinical practice. In order to achieve a pharmacogenetic/pharmacogenomic signature, improvements in study design of future investigations are required, including carefully designed prospective studies. It is imperative to combine known clinical, serological, and molecular markers with consistent outcomes and an adequate health economic evaluation before they can be adopted widely in clinical practice.     

Pharmacoeconomics of long-term treatment of rheumatoid arthritis

Rheumatoid arthritis affects ~ 1% of the population. It is associated with pain, deformity, decreased quality of life and disability that in turn affects patients’ ability to work. A variety of disease-modifying antirheumatic drugs are available to control the disease activity of rheumatoid arthritis. The goal of treatment is to improve patients' quality of life and prevent joint destruction. This paper reviews both the clinical aspects of frequently prescribed disease-modifying antirheumatic drugs and the available cost-effectiveness information. Clinical evidence supports the effectiveness of methotrexate, etanercept, infliximab, gold, hydroxychloroquine, leflunomide, sulfasalazine, penicillamine, cyclosporin, azathioprine, and corticosteroids. The last four of these are associated with greater toxicity and are only used if less toxic drugs are ineffective. The lack of published economic evaluations of disease-modifying antirheumatic drugs highlights the need for such studies to allow efficacious and cost-effective drugs to be used to prevent the long-term complications of uncontrolled rheumatoid arthritis.     

Novel therapies for the treatment of juvenile rheumatoid arthritis (juvenile idiopathic arthritis)

The majority of children with juvenile idiopathic arthritis respond well to conventional treatment. However, some children will have a more aggressive disease course and will be resistant to standard management. Over the past 20 years, growth in our understanding of the immunopathogenesis of juvenile idiopathic arthritis and related diseases has facilitated significant therapeutic advances. In this report, recently released antirheumatic drugs, as well as some treatments currently in development, will be discussed. Biological agents, such as antiTNF and other cytokines inhibitors, and unique drugs, such as thalidomide, provide new opportunities to suppress the inflammation found in severe cases of systemic onset juvenile idiopathic arthritis and can obtain a satisfactory outcome.     

Pharmacological therapy of spondyloarthritis

Introduction: The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs.

Areas covered: A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account.

Expert opinion: Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.     

Current status and new developments in the treatment of psoriasis and psoriatic arthritis with biological agents

Psoriasis is a chronic inflammatory disease affecting 1–3% of the general population. Among psoriatic patients, 5–40% are affected by psoriatic arthritis. Due to the chronic nature of the disease, patients suffer from substantial psychological and financial burdens, thus adding to a significantly impaired quality of life. Traditional systemic therapies for psoriasis, such as methotrexate, cyclosporin A, retinoids or PUVA therapy, have a potential for long-term toxicity and may not always provide sufficient improvement of the disease. The development of novel therapies targeting key steps in the pathogenesis of psoriasis and psoriatic arthritis now provide new and efficient treatment options. Biological therapies for the treatment of psoriasis and/or psoriatic arthritis are defined by their mode of action and can be classified into three categories: the T-cell modulating agents (alefacept and efalizumab), the inhibitors of tumour necrosis factor-α (TNFα blockers, e.g. adalimumab, certolizumab, etanercept, golimumab and infliximab) and the inhibitors of interleukin (IL) 12 and IL-23 (e.g. ustekinumab and briakinumab). This article provides a brief overview of the currently approved biological agents in the European Union and of some newer agents, such as briakinumab, certolizumab and golimumab.     

Discontinued drugs in 2006: pulmonary-allergy,dermatological, gastrointestinal and arthritis drugs

This perspective is the second in a series discussing drugs dropped from development in 2006, with a focus on pulmonary-allergy, dermatological, gastrointestinal and arthritis drugs. A survey of discontinued drugs from 2006 is provided, based on data from the Pharmaprojects database, along with an analysis of biology, mechanisms of action and economic considerations in developing new drugs.     

Perioperative statin therapy: current knowledge and future directions

Perioperative statin therapy has come to represent a cornerstone of risk reduction for millions of patients who undergo cardiac and noncardiac surgeries. While large-scale, robust, randomized controlled studies support the use of statins in cardiac surgery, their role in noncardiac surgery has become ambiguous following concerns regarding scientific misconduct in many pivotal studies. In this edition of the Expert Opinion on Pharmacotherapy, Irwin et al. comprehensively summarize the evidence for perioperative statin treatment. The authors add to this review by providing expert opinions regarding the state of the science and future paths for research and enquiry.