SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Expert review of clinical immunology

0

The prognosis of juvenile idiopathic arthritis (JIA) has changed dramatically due to the availability of novel drugs. Prompt diagnosis and treatment are essential to prevent permanent joint damage. As a result, methods to improve JIA diagnosis and prognosis are of high priority to tailor treatment strategies and maximize their efficacy. Musculoskeletal ultrasound and MRI are more sensitive than clinical examination and radiography in the detection of joint involvement and might play a substantial role to optimize the management of JIA. Areas covered: This review compiles an inventory of potential uses of imaging studies in the modern practice of paediatric rheumatology, together with a critical analysis of the major challenges that are still to be addressed. Imaging appearance of normal growth-related changes of the musculoskeletal system will be discussed. Expert commentary: Knowledge of the evolving patterns of skeletal maturity is paramount to define pathological findings and avoid misinterpretations. Establishing a novel radiological algorithm for a rational use of imaging in JIA is of high priority to allow a speedier integration of imaging into the clinical workflow and decision-making process.

0

The idiopathic inflammatory myopathies (IIM) dermatomyositis and polymyositis are chronic diseases affecting the striated muscles with variable involvement of other organs. Glucocorticoids are considered the cornerstone of treatment, but some patients require adjunctive immunosuppressive agents because of insufficient response to glucocorticoids, flares upon glucocorticoid tapering, or glucocorticoid-related adverse events. Areas covered: The aim of this article was to review (PubMed search until February 2018) the evidence on established and new therapies derived from randomized controlled trials (RCT) on adult dermatomyositis and polymyositis. In addition, key data from open-label trials, case reports and abstracts was included where data from RCT was lacking. Expert commentary: Numerous synthetic and biological immunosuppressive agents are currently available to treat the IIM, sometimes in combination. The choice of the specific medication in the individual patient depends upon the disease phenotype and patient’s characteristics. Exercise improves muscle performance without causing disease flares and should be an integral part of the treatment of the IIM. Prompt diagnosis and treatment can lead to better outcome.

0

The aim of the meta-analysis was to evaluate the association between ten widely studied polymorphisms of interleukin-23 receptor gene (IL-23R) and ankylosing spondylitis (AS).

0

Interleukin-6 (IL-6) is well-known for its pro-inflammatory properties, has been proven to target a wide range of cells in the joint and has been implicated in extra-articular and articular manifestations in rheumatoid arthritis (RA). Tocilizumab (TCZ) is now widely used in patients with active RA and a number of additional agents that target the IL-6 pathways are under development, including sirukumab (SRK). Areas covered: SRK is a IgG1κ human anti-IL-6 monoclonal antibody which binds to IL-6 and prevents IL-6 mediated downstream effects. Initial trial results in phase III studies in patients with RA seemed promising, showing improved results in patients with moderate to severe RA. Data derive from the phase II study and the various SIRROUND studies (phase III). Expert commentary: The available data show that SRK50 mg every 4 weeks or 100 mg every 2 weeks will be effective in treating the RA population, with clinical improvements as early as week 2 and sustained over time. The adverse event profile seems to be similar to TCZ, except for an increased mortality post open-label studies due to infections and cardiovascular events, our knowledge of which will be deepened with post-marketing surveillance and registry data.

0

For successful switching of bio-originators to biosimilars, confidence in the switch is an important criterion. To promote confidence, scientific evidence is critical, but still there are insufficient data for the majority of approved biosimilars. Areas covered: Scientific evidence for switching from bio-originator DMARDs to biosimilars is derived from randomized controlled trials (RCTs) for switching, extension studies of RCTs for the approval process, and real-world observational studies. To identify candidate studies, PubMed was searched to collect appropriate studies in all approved biosimilars for the treatment of rheumatic diseases. In addition, abstracts for scientific meetings were reviewed to discover abstracts focused on switching. To date, we have identified 17 extension studies of RCTs, one RCT, and 17 real-world observational studies. Most real-world studies have originated from CT-P13 and SB4. Switching was definitively safe and effective in most of studies, but some nocebo effects were observed. Expert Commentary: Clear guidelines for switching and data from post-marketing surveillance and registries will be required to confirm existing results on the safety and efficacy of switching from bio-originators to biosimilars. To lessen the nocebo effect against biosimilars, effective educational programs should be provided for all stakeholders, including patients and physicians.

0

Giant cell arteritis (GCA) is the most common large-vessel vasculitis in individuals older than 50 years from Western countries. The goal of the treatment is to achieve improvement of symptoms and clinical remission as well as decrease the risk of severe vascular complications. Areas covered: The review summarizes the main epidemiological and clinical features of GCA and discusses in depth both the classic and the new therapies used in the management of GCA. Expert commentary: Prednisone/prednisolone of 40-60 mg/day is the mainstay in GCA therapy. It yields improvement of clinical features and reduces the risk of permanent visual loss in patients with GCA. Other drugs are used in patients who experience relapses (flares of the disease) or side effects related to glucocorticoids. Methotrexate is the most common conventional immunosuppressive drug used as a glucocorticoid sparing agent. Among the new biologic agents, the most frequently used is the recombinant humanized anti-IL-6 receptor antibody, which is effective to improve clinical symptoms, decrease the cumulative prednisone dose and reduce the frequency of relapses in these patients. Anti-tumor necrosis factor-α therapy is not useful in GCA. Experience with other biologic agents, such as abatacept or ustekinumab, looks promising but it is still scarce.

0

The B7/CD28/CTLA4 signaling cascade is the most thoroughly studied costimulatory pathway and blockade with CTLA4Ig (abatacept) or its derivative belatacept has emerged as a valuable option for pharmacologic immune modulation. Several clinical studies have ultimately led to the approval of belatacept for immunosuppression in kidney transplant recipients. Areas covered: This review will discuss the immunological background of costimulation blockade and recent preclinical data and clinical results of CTLA4Ig/belatacept. Expert commentary: The development of belatacept is a major advance in clinical transplantation. However, in spite of promising results in preclinical and clinical trials, clinical use remains limited at present, in part due to increased rates of acute rejection. Recent efforts showing encouraging progress in refining such protocols might be a step towards harnessing the full potential of costimulation blockade-based immunosuppression.

0

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease (CTD) characterized by vascular dysfunction, fibrosis, inflammation and autoantibodies. The pathophysiology of SSc is not completely understood, and many patients acquire organ or tissue damage despite advances in treatment. Current treatments target affected organs with modest improvements. Areas covered: This review evaluates several treatment strategies for SSc based on involved organs including skin, pulmonary, cardiac, renal, musculoskeletal and gastrointestinal. Currently, pulmonary hypertension and interstitial lung disease are the primary causes of increased mortality. We will outline an approach to treatment of SSc based on disease manifestations and current evidence. Expert commentary: This complex disease is currently treated with therapies developed for similar indications such as for vascular manifestations of SSc using idiopathic pulmonary arterial hypertension treatments. Future directions in this field may include combination and maintenance therapy that is currently used in other autoimmune diseases, and tailoring these treatments according to the patients' phenotype. This will hopefully increase the efficacy of available treatments and decrease mortality from SSc.

0

Common Variable Immunodeficiency Disorders (CVID) are the most frequent symptomatic primary immune defect in adults. Within the broad spectrum of CVID, a proportion of patients present with a predominant T cell phenotype associated with increased mortality. These patients are termed late onset combined immunodeficiency (LOCID) and are currently separated from patients suffering from CVID. Areas covered: We have recently co-discovered a new CVID-like disorder caused by mutations of the NFKB1 gene. Members of this non-consanguineous NZ kindred have a very diverse spectrum of phenotypes in spite of carrying the identical mutation. The proband appears to have the autoimmune variant. The proband’s recently deceased sister best matched LOCID while other family members are less severely affected, including one asymptomatic adult brother, who has an affected daughter. Differences in genetics was one of the main arguments for separating these disorders in the past. Expert commentary: Given the recent advances in the understanding of the genetic basis of these conditions, we present the case that LOCID should now be considered a subset of CVID, rather than a separate disorder. At a clinical level, this distinction is less important but it is imperative these patients are carefully evaluated, the relevant complications are treated and they are offered prognostic information.

0

Several studies have employed microarray-based profiling to predict response to tumor necrosis factor-alpha inhibitors (TNFi) in rheumatoid arthritis (RA); yet efforts to validate these targets have failed to show predictive abilities acceptable for clinical practice.