Barbara Maria Colombo

Anti-TNF-α Inhibitors: A New Therapeutic Approach for Inflammatory Immune-Mediated Diseases: An Update upon Efficacy and Adverse Events

The ongoing progresses in the knowledge of the pathogenic mechanisms of various inflammatory or immune-mediated diseases and the availability of innovative biotechnological approaches have lead to the development of new drugs which add to conventional treatments. TNF-α inhibitors (Infliximab, Adalimumab and Etanercept) have demonstrated efficacy either as monotherapy or in combination with other anti-inflammatory or disease modifying anti-rheumatic drugs (DMARDs). The efficacy and safety profile of the TNF-α inhibitors can be considered, in general, as a class effect. Nevertheless, some differences may exist among the three agents. In this paper, we will briefly review the indications for the use of the three TNF-α inhibitors, the pre-treatment considerations and the reported adverse events.

Maternal arrhythmias during pregnancy.

Introduction.An increased incidence of maternal cardiac arrhythmias is observed during pregnancy and they can range from clinically irrelevant isolated premature beats to debilitating supraventricular and ventricular tachycardias.Discussion.Management of arrhythmias during pregnancy is similar to that in non-pregnant patients. However, the presence of the foetus and the risk of teratogenicity, the haemodynamic changes, the effect of therapy on labour, delivery and lactation must be evaluated. Antiarrhythmic drug selection depends on the specific arrhythmia being treated and the cardiac condition of the mother. Although no drug is completely safe, most are well tolerated and can be given with relatively low risk. Some antiarrhythmic agents, such as propranolol, metoprolol, digoxin and quinidine, have been extensively tested during pregnancy and have proved to be safe; they should therefore, whenever possible, be used as a first-line. For supraventricular tachycardia, intravenous adenosine may be used to terminate the arrhythmia if vagal manoeuvres fail. If possible, drug therapy should be avoided during the first trimester of pregnancy. When drug treatment fails or is not indicated because of the haemodynamic instability of the patient, direct current cardioversion can be used.Conclusion.Most patients with arrhythmias during pregnancy can be treated with an excellent result.

The role of Th17 lymphocytes in the autoimmune and chronic inflammatory diseases.

The emerging role of interleukin-17 as a hallmark proinflammatory cytokine of the adaptive immune system produced by a new T helper cell subset termed “Th17” has received considerable attention. In this review we will focus on recent information regarding IL-17 and its relevance in autoimmune and chronic inflammatory diseases.

Traditional and non traditional risk factors in accelerated atherosclerosis in systemic lupus erythematosus: role of vascular endothelial growth factor (VEGATS Study).

OBJECTIVE To evaluate the role of vascular endothelial growth factor (VEGF) in accelerated atherosclerosis in patients with Systemic Lupus Erythematosus (SLE). METHODS We have enrolled 80 SLE female patients and 80 age-matched healthy control females who underwent a structured interview, physical examination, routine laboratory tests, VEGF plasma level determination and B-mode ultrasonography of carotid arteries to determine carotid intima media thickness (IMT). Framingham risk factors for cardiovascular events were also calculated and VEGF plasma levels were correlated with traditional and nontraditional cardiovascular risk factors. RESULTS SLE was significantly associated with higher mean IMT values (0.74+/-0.15 mm versus 0.59+/-0.12 mm in controls, p<0.001) and higher mean plasma VEGF levels (307.9+/-292.2 pg/mL versus 120.7+/-118.4 pg/mL in controls, p<0.001) independently from age, smoking habits, and Framingham risk factors. A significant correlation was also found between IMT and VEGF values (r=0.25; p<0.001). CONCLUSION We show that SLE patients have increased mean IMT and VEGF values as compared with healthy age-matched controls and that IMT and VEGF values are independently and directly associated with SLE disease.

Emerging biological drugs: a new therapeutic approach for Systemic Lupus Erythematosus. An update upon efficacy and adverse events.

B-cells abnormalities leading to autoantibody production play a central role in Systemic Lupus Erythematosus (SLE) pathogenesis. B-cell targeted therapies, including anti-B lymphocyte stimulator (BLyS) and anti-CD20 monoclonal antibodies, are at forefront of new SLE treatments. Biologic agents targeting specific pathways (i.e. T-B lymphocyte interaction, cytokines and complement) have been also proposed as new tools for SLE treatment. In this review we will focus on biological drugs whose potential efficacy has been evaluated in open-label and randomized clinical trials.

Update upon efficacy and safety of TNF-α inhibitors

The ongoing progresses in the knowledge of the pathogenic mechanisms of various immune-mediated and inflammatory diseases as well as the availability of innovative biotechnological approaches have led to the development of new drugs that add to conventional treatments. Among these, tumor necrosis factor (TNF)-α inhibitors, that is, infliximab, adalimumab, etanercept, golimumab and certolizumab pegol, are now available for clinical use. This editorial discusses the recent indications of TNF-α inhibitors, the pretreatment considerations, the reported adverse events and, finally, the recommendations for its use in pregnancy.

Adalimumab for the treatment of immune-mediated diseases: an update on old and recent indications.

Ongoing progress in understanding the pathogenic mechanisms regulating various immune-mediated and inflammatory diseases, as well as the availability of innovative biotechnological approaches, have lead to the development of new drugs that add to conventional treatments. Among these, tumor necrosis factor (TNF)-α inhibitors such as infliximab, adalimumab, etanercept, golimumab and certolizumab pegol, are now available for clinical use. Adalimumab is a fully recombinant human immunoglobulin G1 monoclonal antibody that specifically binds with high affinity to human TNF-α and inhibits its binding to TNF receptors. Adalimumab was approved by the U.S. FDA in 2002 and was granted approval from the European Medicines Agency in September 2003 for the treatment of moderate to severe rheumatoid arthritis and subsequently for the treatment of ankylosing spondylitis, chronic plaque psoriasis, psoriatic arthritis, juvenile idiopathic arthritis and Crohns disease. In this paper, we will briefly review the structure and biological effects of TNF-α, the old and recent indications of adalimumab, the pretreatment considerations, the reported adverse events and finally, the recommendations for its use in pregnancy.

Anti-Tumor Necrosis Factor-α Treatment with Infliximab for Disseminated Granuloma Annulare

Granuloma annulare (GA) is a chronic inflammatory disease of unknown etiology characterized by the development of plaques preferentially localized to the distal extremities. Spontaneous remission and relapses are quite common and the course of GA is not easy to predict. Moreover, most therapeutic regimens have been used anecdotally and with variable success. We report the case of a 62-year-old White female patient affected by disseminated GA unsuccessfully treated with psoralen plus UVA photochemotherapy, prednisone, and cyclosporine (ciclosporin) who responded to the anti-tumor necrosis factor-a monoclonal antibody infliximab administered intravenously at a dosage of 5 mg/kg at weeks 0, 2, and 6 and thereafter at monthly intervals for 10 additional months. Most of the GA lesions improved within 8 weeks and then slowly resolved within 10 months of treatment. We suggest that infliximab may be proposed as an additional therapeutic option in the treatment of recalcitrant forms of disseminated GA.

Serum vascular endothelial growth factor in allergic rhinitis and systemic lupus erythematosus

Allergic rhinitis (AR) is characterized by an inflammatory reaction sustained by Th2 polarization, whereas systemic lupus erythematosus (SLE) is a typical autoimmune disorder. Vascular endothelial growth factor (VEGF) is a critical mediator of inflammation. The aim of this study was to compare serum VEGF levels in three groups of subjects: 40 normal subjects, 40 allergic patients, evaluated before and after specific immunotherapy, and 40 patients with inactive SLE. Patients who were allergic before immunotherapy had the lowest VEGF serum levels, which significantly increased after treatment; SLE patients had the highest VEGF serum levels. This comparative study provides evidence that serum VEGF levels depend on the type of immune response: they are high in autoimmune disease and low in Th2-polarized allergic reaction. The relevance of this phenomenon is further apparent, as it is also observed in patients with inactive disease.

Intima-media thickness: a marker of accelerated atherosclerosis in women with systemic lupus erythematosus.

Abstract:  Accelerated atherosclerosis is an emerging problem in patients with systemic lupus erythematosus (SLE). We planned an observational study to determine whether in patients with SLE carotid intima‐media thickness (IMT) represents an early sign of accelerated atherosclerosis and to confirm that SLE adds to the traditional cardiovascular Framingham risk factors. Thirty females with SLE (age 18–65 years) underwent anamnestic, clinical, and laboratory evaluation and B‐mode ultrasonography of carotid arteries, which provides a direct and noninvasive assessment of subclinical atherosclerosis. IMT measurements were performed on the right and left common carotid arteries 1.0 cm proximal to the carotid bulb and the mean IMT value was calculated with a dedicated software. The Framingham Point Score was also calculated for each subject. SLE patients showed a mean IMT value of 0.73 ± 0.12 (SD) mm. This value is significantly (P < 0.05) higher than that reported for an age‐matched healthy female control population (0.66 ± 0.11 SD mm). A preliminary evaluation of the Framingham Point Score, estimating the 10‐year risk for women to develop cardiovascular events, indicated an increased risk of early cardiovascular events in SLE patients. In our study we have shown that patients with SLE have an increased mean IMT value compared with a healthy females control. Moreover, the evaluation of the Framingham Point Score suggests that SLE is an additional risk factor for cardiovascular disease.