Patients with moderate-to-severe psoriasis recapture clinical response during re-treatment with etanercept

Background  Patients with psoriasis experience remission and gradual reappearance of erythematous and scaly plaques and require individualized treatment over time. A goal of psoriasis treatment is to provide optimal efficacy with a flexible therapeutic regimen that may include treatment pauses.
Objectives  To determine whether patients receiving initial treatment with etanercept who then pause therapy would subsequently recapture response during re-treatment.
Patients and methods  A post-hoc analysis of 226 patients with moderate-to-severe psoriasis from a large multicentre trial was performed. Patients had received etanercept 50 mg twice weekly subcutaneously until a target clinical response had been achieved, then had paused treatment and eventually relapsed. They were then re-treated with etanercept 25 mg twice weekly. The number of patients recapturing a Physician Global Assessment (PGA) of psoriasis rating of ≤ 2 (clear, almost clear or mild) on first re-treatment was assessed. Patient satisfaction during the initial treatment and first re-treatment period was also determined.
Results  A total of 187 (83%) patients recaptured the target clinical response of a PGA of ≤ 2 after re-treatment. The majority of patients [219 of 226 (97%)] reported satisfaction with etanercept re-treatment. No new safety concerns emerged during re-treatment.
Conclusions  In this post-hoc analysis, patients with psoriasis who were re-treated with etanercept 25 mg twice weekly effectively recaptured clinical responses that patients found satisfactory. A flexible treatment option is available to dermatologists and patients for individualized care.     

治疗类风湿性关节炎的新药

非甾体类抗炎药(NSAID)的抗炎镇痛作用主要通过抑制环氧合酶(COX),阻断前列腺素及与疼痛、炎症相关的炎症介质的生物合成来实现,但胃肠道和肾毒性副作用限制了其应用,而大多数NSAID毒性是由非特异性COX抑制引起的.塞来克西(celecoxib)系第一个特异性COX-2抑制剂,其临床效果与传统NSAID相似,但安全性较好.来氟米特是一个新的病症缓解性抗关节炎药,通过抑制嘧啶合成而减少关节炎炎症,来氟米特与甲氨蝶呤一样有效,但无骨髓毒性.etanercept是FDA批准治疗类风湿性关节炎的第一个生物制剂,有效且只有轻微的注射部位反应.     

Anti-drug antibodies in psoriasis: a critical evaluation of clinical significance and impact on treatment response

TNF inhibitors and anti-p40IL12/23 monoclonal antibodies are efficacious treatments for moderate-to-severe psoriasis. However, the formation of anti-drug antibodies (ADA) with biologics may prevent patients from achieving a full clinical response. ADA have been reported in patients treated with etanercept, infliximab, adalimumab or ustekinumab at rates of 0–18.3%, 5.4–43.6%, 8.8–44.8% and 3.8–5.4%, respectively. Antibodies against etanercept have no apparent effects on clinical response, whereas antibodies against infliximab or adalimumab have been associated with diminished clinical response. The significance of ADA against ustekinumab is yet to be determined. Data regarding management strategies to counteract ADA formation and their effects are limited in psoriasis patients. However, some evidence suggests that concomitant immunomodulators such as methotrexate may suppress ADA development in psoriasis. ADA specific to one biologic do not appear to carry cross-linking potential with other biologic agents. ADA formation needs to be considered as a possible factor contributing to diminished response from biologic agents.     

Reduction of inflammatory slan (6‐sulfo LacNAc) dendritic cells in psoriatic skin of patients treated with etanercept

Dermal dendritic cells (DCs) play a central role in the immunopathology of psoriasis. We previously identified slanDCs as pro‐inflammatory TNF‐α, IL‐23‐ and IL‐12‐producing DCs in human blood and as prominent inflammatory dermal TNF‐α secreting and CD11c‐positive DC subset in psoriasis. Here, we ask for the effects of TNF‐α‐inhibition on inflammatory slanDCs in skin and blood of 10 patients with psoriasis during 24 weeks of treatment with etanercept. Treatment with etanercept reduced the frequency of dermal slanDCs but did not induce apoptosis as determined by lack of increased active caspase‐3‐expression. In parallel, we found increased frequencies of slanDCs in blood which expressed lower levels of HLA‐DR. Stimulating slanDCs isolated from the blood of healthy donors in vitro induced a strong production of IL‐1β, IL‐6, IL‐23 and IL‐12p70. This capacity was efficiently reduced in the presence of etanercept, thereby indicating that TNF‐α is an autocrine stimulus for maturation and pro‐inflammatory cytokine production of slanDCs. In vivo, we noticed that treatment with etanercept did reduce the number of dermal slanDCs in parallel to the overall expression of TNF‐α and IL‐23p19. However, successful treatment did not down‐regulated the percentage of dermal slanDCs that stained positive for TNF‐α and IL‐23p19 indicating that remaining slanDCs kept their pro‐inflammatory capacity. This study provides novel insights into the immune regulatory properties of etanercept at the level of inflammatory slanDCs in vivo in skin and blood as well as in vitro.     

Etanercept for refractory asthma therapy

Asthma is a chronic disease of the airways in which inflammation causes bronchial hyper-reactivity and consequent asthma attacks triggered by various stimuli. The bronchospasm attacks are usually relieved by short-acting β₂ agonists, and inflammation and bronchial hyper-reactivity are reduced by maintenance therapy and, in particular, by inhaled corticosteroids. In milder asthma subjects, airway inflammation is dominated by eosinophils, whereas in more severe asthma increased neutrophil counts were detected. In severe/refractory asthma, TNF-α is known to play a role in the maintenance of neutrophilic inflammation and of bronchial hyper-responsiveness and is not influenced by corticosteroid therapy. Etanercept, a TNF-α-blocking agent, could represent one of the potential therapies for refractory asthma based on demonstrated safety and efficacy.     

Emerging biotherapies for Sjögren's syndrome

Importance of the field: Sjögren's syndrome (SS) is an autoimmune epithelitis. This exocrinopathy is frequently associated with extraglandular complications, and the patients are at risk of developing B cell lymphoma. Given the lack of disease-modifying drugs, and the fact that SS is a quintessential B-cell mediated disease, attention has recently been focused on biotherapies.

Areas covered in this review: Despite negative grounds, TNF-α antagonists have been tested in the disease, and proven not be efficient. However, B-cell depleting therapy using anti-CD20 antibodies such as rituximab, which is a chimeric mAb, has shown promise in the field, while anti-CD22 mAb seems to be less active.

What the reader will gain: New treatments against the B-cell activating factor of the TNF family are about to be tested, or replaced by receptor immunoglobulin decay protein.

Take home message: B-cell depleting therapies seem promising in SS, but no data are, thus far, available on treatments targeting B-cell activating factor of the TNF family.     

The treatment of juvenile arthritis

Until recently, two different classification systems for juvenile arthritis (JA) were utilised, each with its own terminology and subclassification (Table 1) [1]. It has been recognised that particularly within the polyarticular and pauci-articular groups, many distinct subsets exist each with a different prognosis. As a result, a new classification system for JA has been developed (Table 2) [2]. It is hoped that this will allow more accurate assessment of incidence and aetiology of the various subtypes in future generations and in time will allow therapy to be targeted at those most likely to achieve benefit. Since there is a new classification system for JA, the vast majority of published clinical studies were performed using the old classification system. For the purposes of this review, unless otherwise stated, the American College of Rheumatology classification will be used. This is outlined in Table 1 with clinical features of the major subtypes described in Table 3. This review will cover current best practice and discuss future directions for research using the recent advances in the treatment of rheumatoid arthritis (RA) as a model.     

Who is afraid of biosimilars? Openness to biosimilars in an Australian cohort of patients with rheumatoid arthritis

Biosimilars are increasingly adopted to improve affordability of biologics. An effective introduction of biosimilars requires an understanding of patient acceptance of these agents. We performed a cross‐sectional study of 132 patients with rheumatoid arthritis prior to the introduction of biosimilar switching or prescribing in this cohort. Despite being unfamiliar with biosimilars, most patients are willing to accept biosimilar medicines if recommended by their rheumatologist. Patient concerns about biosimilar uptake mainly focus on concerns about its efficacy. There is a significant correlation between patient attitudes towards biosimilar and generic medicines.     

Biologics in oral medicine: principles of use and practical considerations

Oral Diseases (2012) 18, 525-536 Biologic therapies are relatively innovative treatments aimed at modulating lymphocytes or cytokines. There are currently three broad classes of biologic therapies, tumour necrosis factor-alpha inhibitors, lymphocyte modulators and interleukin inhibitors; all are increasingly used in the treatment of inflammatory immune-mediated conditions, and several have potential applications in oral medicine. Guidelines for their use in licensed indications (e.g. rheumatoid arthritis, psoriasis, inflammatory bowel disease) include recommendations and guidance for patient selection and subsequent monitoring with discussion of potential adverse effects. An understanding of these is important when managing patients receiving biologic therapy for systemic disease, and compliance is essential in any use in oral medicine. Key aspects of current guidance are presented with particular emphasis on their relevance to clinicians working within oral and maxillofacial medicine/pathology/surgery and in specialist practice.