Short‐term effects of the TNFα antagonist infliximab on the acute phase reaction and activities of daily life in patients with rheumatoid arthritis

Objective. To investigate the short‐term effects of the tumour necrosis factor alpha (TNFα) antagonist infliximab on the acute phase reaction and activities of daily life (ADL) in patients with rheumatoid arthritis (RA). Methods. Fourteen patients with active RA were treated with an intravenous infusion of 200?mg infliximab. The values of the erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), fibrinogen, granulocyte count, lymphocyte count, platelet count and a patient questionnaire score on ADL, the Health Assessment Questionnaire (HAQ), were obtained at baseline and on days 4 and 14. The significance levels and effect sizes (ESs) of the changes from baseline were calculated. Results. Changes by day 4: The ESs and significance levels were: CRP 1.7, p<0.005; lymphocyte count 1.4, p<0.005; fibrinogen 0.9, p<0.005; ESR 0.7, p<0.005; and HAQ 0.6, p<0.01. Changes by day 14: CRP 1.6, p<0.005; ESR 1.5, p<0.005; fibrinogen 1.3, p<0.005; lymphocyte count 1.0, p<0.005; granulocyte count 0.7, p<0.05; and HAQ 0.6, p<0.05. Conclusion. CRP, fibrinogen and ESR showed the largest ESs and were thus the most sensitive variables showing the early effect of infliximab in this study. The score on ADL (HAQ) showed less ES, but still significant short‐term improvements.     

英夫利西单抗联合甲氨蝶呤治疗早期严重类风湿性关节炎

目的了解英夫利西单抗及甲氨蝶呤联合应用对早期严重类风湿性关节炎的临床疗效。方法 78例早期严重类风湿性关节炎患者随机分为英夫利西单抗组、英夫利西单抗联合甲氨蝶呤组及甲氨蝶呤组,治疗前作相应的临床、实验室检查后,英夫利西单抗以每次剂量3 mg/kg静脉滴注,第0、26、周以后每隔8周用药1次;甲氨蝶呤每周10 mg,治疗后对患者临床观察指标进行比较,并进行疗效评价。结果英夫利西单抗联合甲氨蝶呤组治疗24周后,关节炎症症明显得以控制,达到美国风湿学会症状体征20%改善(ACR20)、美国风湿学会症状体征50%改善(ACR50)、美国风湿学会症状体征70%改善(ACR70)的分别为90%、64%及39%,与另外两组比较差异有统计学意义(P<0.01)。结论英夫利西单抗与甲氨蝶呤联合应用对早期严重类风湿性关节炎有显著疗效。     

Infliximab protects against pulmonary emphysema in smoking rats

Background  It is widely accepted that tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis of emphysema. This study aimed at investigating the protective effects of anti-TNF-α antibody, infliximab, in the development of emphysema induced by passive smoking in rats.

Methods  Thirty-nine rats were randomly divided into a normal control group (group 1), an emphysema group (group 2), and an infliximab-intervention group (group 3). Rat models of emphysema were established by exposure to cigarette smoking daily for 74 days. After 1 month, the infliximab intervention group was treated with infliximab via subcutaneous injection. The levels of TNF-α, IL-8 and vascular endothelial growth factor (VEGF) in bronchoalveolar lavage fluid (BALF) were measured with enzyme linked immunosorbent assay (ELISA). The number and classification of cells in the BALF were measured. Lung tissue sections stained by hematoxylin and eosin (HE) were observed, and mean linear intercept (MLI) and mean alveolar numbers (MAN) were measured. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods were used to examine the percentage of positive cells and distribution of apoptotic cells.

Results  The levels of TNF-α and IL-8 in BALF were higher in group 2 than in group 1 and group 3. The MLI was greater in group 2 than that in group 1 and group 3 while MAN was decreased. The concentration of VEGF in BALF of group 2 was significantly decreased as compared with group 1. The total cells and neutrophils number was significantly increased in group 2 as compared with group 1 and group 3, so was the percentage of neutrophils. The number of TUNEL positive cells in the alveolar septa was significantly increased in group 2 as compared with group 1 and group 3.

Conclusion  Infliximab protects against cigarette smoking-induced emphysema by reducing airway inflammation, attenuating alveolar septa cell apoptosis and improving pathological changes.

     

Are biosimilars approved for use in psoriasis safe enough to replace leading biologic therapies? A review

ABSTRACT

Introduction: Many tumor necrosis factor (TNF)-alpha ‘biosimilar’ agents have been approved for the treatment of psoriasis and other autoinflammatory conditions. These biosimilars have the same structure as the originator biologic and have been shown to be equivalent in terms of safety and efficacy. However, given the method by which biosimilars are manufactured, they are not exact replicas of the originator, unlike generic forms of non-biologic medications. Therefore, there is controversy regarding whether these agents should be considered interchangeable with their originator biologics.

Areas covered: The objective of this review is to summarize the safety data for each of the approved TNF-alpha biosimilars to determine whether or not these agents have appropriate safety profiles to replace their originator biologics.

Expert opinion: Based on extrapolation of phase III investigations in patients with rheumatologic diseases, each of the approved anti-TNF agents have comparable efficacy, tolerability, and safety profiles to their originators. Studies in patients with psoriasis are more limited. Transitioning from a biologic to its biosimilar has also been shown to be similarly safe and immunogenetic compared to maintenance therapy with the originator. More post-marketing studies are needed to demonstrate the long-term safety in patients with psoriasis.     

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

The Asia–Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia–Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all‐encompassing, and future revisions are likely as new data continue to emerge.     

沙利度胺联合英夫利西治疗克罗恩病患者的临床效果

目的研究沙利度胺联合英夫利西治疗克罗恩病患者的临床效果。方法选择2017年9月至2018年9月我院收治的106例克罗恩病患者为研究对象,采用随机数字法将其分为英夫利西组(53例,英夫利西)和沙利度胺+英夫利西组(53例,沙利度胺联合英夫利西)。比较两组的临床疗效。结果治疗2个月后,沙利度胺+英夫利西组的IFN-γ、TNF-ɑ、IL-8、CRP、VEGF水平、CDAI评分、ESR、CD4^+、CD3^+及不良反应总发生率明显低于英夫利西组,CD8^+和临床治疗总有效率明显高于英夫利西组(P<0.05)。结论克罗恩病患者应用沙利度胺联合英夫利西治疗的效果显著,可推广应用。