Golimumab for the treatment of axial spondyloarthritis.

INTRODUCTION: Anti-TNF drugs have represented an epochal revolution in the treatment of rheumatoid arthritis and spondyloarthritis. In the field of axial spondyloarthritis, golimumab, a fully human monoclonal anti-TNFα administered subcutaneously every 4 weeks, has shown significant efficacy and good safety in patients with ankylosing spondylitis. More recently, it was also indicated as an effective treatment for patients suffering from non-radiographic axial spondyloarthitits. Areas covered: A systematic literature search was completed, using the largest electronic databases (Medline, Embase and Cochrane), with the aim to review all data concerning the administration of golimumab in patients suffering from axial spondyloartritis. Expert opinion: In the 16-week GO-AHEAD study, golimumab was effective in patients with non-radiographic spondyloarthritis with high levels of CRP and/or positive MRI findings, but not in subjects with both negative CRP and MRI. This finding allows for the addressing the of anti-TNF treatment more specifically. Preliminary data concerning an open-label extension of the GO-AHEAD study outlined the high retention-rate of the drug at 52 weeks. The production of antibodies against golimumab is rare and it seems to exert scarce influence on the drug performances. In conclusion, golimumab appears as a very useful and well tolerated anti-TNF agent.

Improvements in diagnostic tools for early detection of psoriatic arthritis.

INTRODUCTION: Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease characterized by a wide clinical spectrum. The early diagnosis of PsA is currently a challenging topic. Areas covered: The literature was extensively reviewed for studies addressing the topic area "diagnosis of psoriatic arthritis". This review will summarize improvements in diagnostic tools, especially referral to the rheumatologist, the role of patient history and clinical examination, laboratory tests, and imaging techniques in getting an early and correct diagnosis of PsA. Expert commentary: Due to the heterogeneity of its expression, PsA may be easily either overdiagnosed or underdiagnosed. A diagnosis of PsA should be taken into account every time a patient with psoriasis or a family history of psoriasis shows peripheral arthritis, especially if oligoarticular or involving the distal interphalangeal joints, enthesitis or dactylitis. Magnetic resonance imaging and ultrasonography are useful for diagnosing PsA early, particularly when isolated enthesitis or inflammatory spinal pain occur.

Rheumatic manifestations of hepatitis C virus chronic infection: Indications for a correct diagnosis.

Hepatitis C virus (HCV) is a hepato- and lymphotropic agent that is able to induce several autoimmune rheumatic disorders: vasculitis, sicca syndrome, arthralgias/arthritis and fibromyalgia. The severity of clinical manifestations is variable and sometimes life-threatening. HCV infection can mimic many primitive rheumatic diseases, therefore, it is mandatory to distinguish HCV-related manifestations from primitive ones because the prognosis and therapeutic strategies can be fairly dissimilar. The new direct-acting antivirals drugs can help to avoid the well-known risks of worsening or new onset of autoimmune diseases during the traditional interferon-based therapies.

Relationship of Psoriatic Arthritis to Other Spondyloarthritides.

In the early 1970s, Moll and co-workers formulated the unified concept of spondyloarthritides, a group of conditions sharing similar clinical features. Subsequently, criteria for their classification have been proposed by Amor and coworkers, the European Spondylarthropathy Study Group, and the Assessment in SpondyloArthritis international Society. Opinion, however, is divided between those who believe that the different entities of the complex represent the variable expression of the same disease ("lumpers") and those who think that these should be considered separately but under the same umbrella ("splitters"). Several sets of criteria have been proposed for psoriatic arthritis (PsA), the most recent being the ClASsification for Psoriatic Arthritis (CASPAR) criteria. According to some authors, there are persuasive arguments to support the view of PsA as a distinct entity.

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.

An update on the management of hepatitis C virus-related arthritis.

INTRODUCTION: Hepatitis C virus (HCV)-related arthritis is an uncommon disease belonging to the autoimmune disorders due to the chronic stimulus exerted by the virus on the immune system. It shows two clinical subsets: a symmetrical polyarthritis resembling rheumatoid arthritis but less aggressive and an intermittent mono-oligoarthritis involving the lower limbs. AREAS COVERED: We extensively review the current literature using the largest electronic databases (MEDLINE, EMBASE and COCHRANE) with regard to HCV-related arthritis (HCVrA) and studies focusing on the co-existence of HCV and other kinds of arthritides. EXPERT OPINION: The therapeutic approach to HCVrA remains largely empirical, because few studies have been published on this topic. Mainstream treatment based on the administration of hydroxychloroquine and low doses of corticosteroid is still largely preferred. Cyclosporine represents a useful alternative due to its antiviral properties. Anti-TNF agents are safe, but their hypothetic use appears excessive for a mild disorder such as HCVrA. IFN-α (and more recently pegylated IFN-α) when administered as a component of the combined (IFN-α + ribavirin) anti-HCV therapy can promote the appearance or the worsening of several autoimmune HCV-related disorders, including arthritis. New and forthcoming antiviral molecules will be used in the near future for a revolutionary IFN-free treatment.

Advances in the management of psoriatic arthritis.

Psoriatic arthritis (PsA), which affects musculoskeletal structures, skin and nails, is a heterogeneous chronic inflammatory disease with a wide clinical spectrum and variable course. Patients with PsA are more likely than healthy individuals to have metabolic syndrome or cardiovascular disease. To include these comorbidities, 'psoriatic disease' has been suggested as an umbrella term. The management of PsA has changed tremendously over the past decade owing to early diagnosis and improvement in treatment strategies, including, early referral from dermatologists and primary-care physicians to rheumatologists, early initiation of therapy, treating to the target of remission or low disease activity, and advances in pharmacological therapy. Outcome assessment is also improving, because of validated instruments for clinical disease manifestations. The commercialization of TNF blockers, including adalimumab, etanercept, golimumab and infliximab, is representative of a revolution in the treatment of PsA. A new anti-TNF agent, certolizumab pegol, and a fully human monoclonal antibody against IL-12 and IL-23, ustekinumab, are approved for the treatment of active PsA. The efficacy of ustekinumab suggests that inhibiting the type 17 T helper pathway might be an alternative to blocking TNF. PsA management must now use improved measures to predict patient outcomes and define remission, and develop better-targeted therapies.

Safety of anti-tumor necrosis factor agents in psoriatic arthritis - an update.

INTRODUCTION: Tumor necrosis factor (TNF) blockers have represented a real revolution in the treatment of rheumatoid arthritis and spondyloarthritides (SpAs). In the case of psoriatic arthritis (PsA), anti-TNF agents are much more effective than conventional disease modifying antirheumatic drugs on all manifestations of the disease, that is, axial involvement, peripheral arthritis, peripheral enthesitis, dactylitis and skin lesions. A complete understanding of their safety is fundamental in clinical practice. AREAS COVERED: This article addresses the safety of anti-TNF therapy in PsA. A systematic literature review was performed using the largest electronic databases (MEDLINE, EMBASE and COCHRANE). The reported data were derived from randomized controlled trials, open-observational studies and meta-analyses. Useful information derived from the experiences in rheumatoid arthritis has also been reported. EXPERT OPINION: Anti-TNF therapies are as safe as conventional disease-modifying antirheumatic drugs in the management of psoriatic arthritis when the candidate patients are accurately selected. An adverse event could still occur when the patient is managed according to current national and/or international recommendations; therefore, tight controls aimed to detect adverse events early is mandatory.

Can we reduce the dosage of biologics in spondyloarthritis?

TNF blockers have revolutionized the management of spondyloarthritis (SpA). To date, four anti-TNFα agents (etanercept, infliximab, adalimumab, golimumab) have been approved for the management of ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The first objective in the management of AS and PsA with TNF inhibitors is to reduce disease activity to clinical remission or low disease activity. After remission has been achieved, this state should be maintained as long as possible. However, the financial burden associated with the cost of anti-TNF agents as well as concerns about their long-term safety suggest reducing the dosage of the drug or discontinuing the therapy in the hopes of drug-free remission. The aim of this review is to examine what has, till now, been published on this topic in axial SpA, which includes AS and non-radiographic axial SpA (nr-axSpA), peripheral SpA and PsA. Discontinuation of therapy in axial SpA is not possible in the majority of patients, while on the contrary, reducing the dosage often is. In some patients with peripheral SpA and PsA it is also possible to discontinue therapy and to achieve drug-free remission.

New insights in occult psoriatic arthritis.

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.

The radiological assessment of axial involvement in psoriatic arthritis.

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.

Pharmacoeconomic issues in psoriatic arthritis.

Therapies for psoriatic arthritis were inadequate until a short time ago. Nonsteroidal antiinflammatory drugs are helpful in relieving symptoms but do not prevent joint damage. Traditional disease-modifying antirheumatic drugs are used to control symptoms, but there is no evidence that they prevent or significantly slow the progression of structural damage in peripheral joints. The introduction of tumor necrosis factor-α (TNF-α) blocking agents has opened new horizons. These drugs lessen signs and symptoms of inflammation, enhance functional capacity and quality of life, and inhibit structural joint damage. On the other hand, TNF-α blockers are very costly and not easily available to all patients, whether they rely on a national health system or on private insurance. Pharmacoeconomic studies on these drugs so far have shown that they are cost-effective on both the musculoskeletal and skin manifestations of psoriatic disease, offering good value for money.

Etanercept in spondyloarthropathies. Part I: current evidence of efficacy.

Etanercept is a recombinant soluble tumour necrosis factor alpha receptor administered subcutaneously at the dose of 50 mg weekly (or 25 mg/twice weekly) for the treatment of the main chronic arthritides: rheumatoid arthritis and spondyloarthropathies. It shows high qualities in terms of efficacy and manageability. Favourable results were reported in all localisations of spondyloarthropathies: axial disease, peripheral arthritis, and enthesitis. In particular, several studies demonstrated its efficacy on the clinical and functional indicators of ankylosing spondylitis. Similar data were also reported for psoriatic arthritis in which, in addition, a significant reduction in the progression of erosive damages was widely described. Furthermore, although only a few studies are available, very interesting results have been obtained in patients suffering from undifferentiated spondyloarthropathies and severe enthesitis.

Etanercept in spondyloarthopathies. Part II: safety and pharmacoeconomic issues.

Etanercept (ETN) and other anti-TNF-α agents have revolutionised the management of spondyloarthropathies (SpA). With the increasingly widespread and prolonged use of these drugs an assessment of their long-term safety is extremely important. An additional concern regarding biological agents is their higher costs compared with conventional drugs. We examined safety data regarding ETN from clinical reports, clinical trials, review articles, databases and registries. In addition, evidence was reviewed about the cost effectiveness of ETN in the treatment of patients with SpA. Our review suggests that ETN is well tolerated as long-term, continuous treatment of SpA with a favourable risk-benefit ratio maintained from 4 to 5 years. Diversity in structure and mode of action could explain some differences in the safety profile of ETN with respect to the other anti-TNF agents. In particular, ETN is less immunogenic and is less likely to induce tuberculosis re-activation than the other TNF-α antagonists. Although ETN is considerably more expensive than conventional therapy, it reduces direct and indirect costs associated to SpA by improving disease activity and quality of life. Recent pharmacoeconomic studies have demonstrated its cost-effectiveness in the treatment of SpA.

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-alpha 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-alpha blockers, IL-1, -6, -12, -23 and -17 inhibitors, co-stimulator modulation inhibitors, B-cell depleting agents, small molecules and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand inhibitors. TAKE HOME MESSAGE: The currently available anti-TNF-alpha blocking agents have revolutionized the management of PsA. However, there is a need for more effective and safer drugs.

Treatment strategies for early psoriatic arthritis.

BACKGROUND: Until a few years ago, the early diagnosis of psoriatic arthritis (PsA) did not receive much attention, especially in view of the lack of drugs capable of altering the disease course. This changed with the introduction of the TNF-alpha-blocking agents, as a result of which the early diagnosis of PsA is now a topic of great interest. OBJECTIVE: The aim of the study was to review the treatment for PsA in order to determine the optimal approach to managing early disease. METHODS: The systematic review performed by members of GRAPPA (Group of Research and Assessment of Psoriasis and Psoriatic Arthritis) was integrated with data from more recent studies. RESULTS/CONCLUSION: After making the diagnosis of PsA, the next step is to stage of the disease with the aim of establishing the prevalent manifestation (peripheral arthritis, peripheral enthesitis, axial involvement and dactylitis) and degree of severity (mild, moderate or severe) of the disease. Each patient should be treated according to the defined disease status following the suggested treatment algorithms.

Pharmacological management of SAPHO syndrome.

The SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome (SaS) includes different skeletal manifestations such as recurrent multifocal osteomyelitis, osteitis and arthritis, which are frequently associated with different forms of skin pustulosis (palmoplantar pustulosis, pustular psoriasis and severe acne). This syndrome is strictly related to the spondyloarthopathies (particularly to psoriatic arthritis) and many SaS cases fulfil the classification criteria for the spondyloarthopathies. Because SaS is an uncommon disease, current knowledge regarding its therapy is based on limited experiences gained by treating mainly small groups of patients. As a consequence, its treatment is still empiric. Several drugs (including NSAIDs, corticosteroids, sulfasalazine, methotrexate, ciclosporin, leflunomide, calcitonin and so on) have been administered and obtained conflicting results. The use of antibiotics, due to the isolation of Propionibacterium acnes from the bone biopsies of several subjects with SaS, has not represented a turning point in therapy, although some patients are responsive to this treatment. Initial reports concerning the administration of bisphosphonates (pamidronate and zoledronic acid) and of an anti-TNF-alpha agent (infliximab) are very promising for the future. In any case, larger, multi-centre, controlled, double-blind studies are required to emerge from the present pioneering phase.