Abstract:
BACKGROUND:Ustekinumab (CNTO 1275) and briakinumab (ABT-874) are monoclonal antibodies that target the standard p40 subunit of the cytokines interleukin-12 and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of Crohn's disease. OBJECTIVES:The objectives of this review were to assess the efficacy and safety of anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease. SEARCH METHODS:The following databases were searched from inception to September 16, 2014: PubMed, MEDLINE, EMBASE, and the Cochrane Library (CENTRAL). References and conference abstracts were searched to identify additional studies. SELECTION CRITERIA:Randomized controlled trials (RCTs) trials in which monoclonal antibodies against IL-12/23p40 were compared to placebo or another active comparator in patients with active Crohn's disease were included. DATA COLLECTION AND ANALYSIS:Two authors independently screened studies for inclusion and extracted data. Methodological quality was assessed using the Cochrane risk of bias tool. The primary outcome was failure to induce clinical remission, defined as a Crohn's disease activity index (CDAI) of < 150 points. Secondary outcomes included failure to induce clinical improvement, serious adverse events, and withdrawals due to adverse events. Clinical improvement was defined as decreases of > 70 or > 100 points in the CDAI from baseline. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each outcome. A fixed-effect model was used to pool data. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. MAIN RESULTS:Four randomized controlled trials (n = 955 patients) met the inclusion criteria. A low risk of bias was assigned to all studies. The two briakinumab trials were not pooled due to differences in doses and time points for analysis. In both studies there was no statistically significant difference in remission rates. One study (n = 79) compared doses of 1 mg/kg and 3 mg/kg to placebo. In the briakinumab group 70% (44/63) of patients failed to enter clinical remission at 6 or 9 weeks compared to 81% (13/16) of placebo patients (RR 0.86, 95% CI 0.65 to 1.14). Subgroup analysis revealed no significant differences by dose. The other briakinumab study (n = 230) compared intravenous doses of 200 mg, 400 mg and 700 mg with placebo. Eighty-four per cent (154/184) of briakinumab patients failed to enter clinical remission at six weeks compared to 91% (42/46) of placebo patients (RR 0.92, 95% CI 0.83 to 1.03). Subgroup analysis revealed no significant differences by dose. GRADE analyses of the briakinumab studies rated the overall quality of the evidence for the outcome clinical remission as low due. Based on the results of these two studies the manufacturers of briakinumab stopped production of this medication. The two ustekinumab studies (630 patients) were pooled despite differences in intravenous doses (i.e. 1mg/kg, 3 mg/kg, 4.5 mg/kg, and 6 mg/kg), however the subcutaneous dose group was not included in the analysis, as it was unclear if subcutaneous was equivalent to intravenous dosing. There was no statistically significant difference in remission rates. At week six, 85% (356/420) of ustekinumab patients failed to enter remission compared to 89% (142/159) of placebo patients (RR 0.94, 95% CI 0.88 to 1.01). Subgroup analysis showed no statistically significant difference by dose. There were statistically significant differences in clinical improvement between ustekinumab and placebo-treated patients. In the ustekinumab group, 55% (230/420) of patients failed to improve clinically (i.e. 70-point decline in CDAI score), compared to 72% (115/159) of placebo patients (RR 0.75, 95% CI 0.66 to 0.86). Subgroup analysis revealed significant differences compared to placebo for the 1 mg/kg, 4.5 mg/kg and 6 mg/kg dosage subgroups. Similarly for a 100-point decline in CDAI, 62% (262/420) of patients in the ustekinumab group failed to improve clinically compared to 78% (124/159) of placebo patients (RR 0.79, 95% CI 0.71 to 0.89). Subgroup analysis showed a significant difference compared to placebo for the 4.5 mg/kg dose group. GRADE analyses of the ustekinumab studies rated the overall quality of the evidence for the outcomes clinical remission and clinical response as moderate. There were no statistically significant differences in the incidence of adverse events, serious adverse events or withdrawal due to adverse events. Sixty-seven per cent (316/473) of ustekinumab patients developed at least one adverse event compared to 73% (135/184) of placebo patients (RR 0.92, 95% CI 0.83 to 1.03). A GRADE analysis indicated that the overall quality of the evidence for this outcome was high. Six per cent (29/473) of ustekinumab patients had a serious adverse event compared to 8% (14/184) of placebo patients (RR 0.81, 95% CI 0.44 to 1.49). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low. The most common adverse events in briakinumab patients were injection site reactions and infections. Infections were the most common adverse event in ustekinumab patients. Worsening of Crohn's disease and serious infections were the most common serious adverse events. AUTHORS' CONCLUSIONS:Although we are uncertain about the efficacy of ustekinumab for induction of remission, moderate quality evidence suggests that ustekinumab may be effective for induction of clinical improvement in patients with moderate to severe CD. Due to small numbers of patients in dose subgroups the optimal dosage of ustekinumab is unclear. Briakinumab and ustekinumab appear to be safe. Due to sparse data we were unable to determine the risk of serious adverse events. Further studies are required to determine the efficacy and safety of ustekinumab in patients with moderate to severe CD. The results of three phase III trials that are currently underway will provide important new information.
journal_name
Cochrane Database Syst Revjournal_title
The Cochrane database of systematic reviewsauthors
Khanna R,Preiss JC,MacDonald JK,Timmer Adoi
10.1002/14651858.CD007572.pub2subject
Has Abstractpub_date
2015-05-05 00:00:00pages
CD007572issue
5issn
1469-493Xpub_type
杂志文章,meta分析,评审abstract:BACKGROUND:Pulmonary arteriovenous malformations are abnormal direct connections between the pulmonary artery and pulmonary vein which result in a right-to-left shunt. They are associated with substantial morbidity and mortality mainly from the effects of paradoxical emboli. Potential complications include stroke, cere...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD008017.pub4
更新日期:2015-01-29 00:00:00
abstract:BACKGROUND:Breastmilk remains the optimal form of enteral nutrition for term and preterm infants until up to six months postnatal age. Mothers of preterm infants who have not established suck feeds must express their breastmilk and often have difficulty in maintaining sufficient volume for their infants' needs (Donath ...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD005544.pub2
更新日期:2012-03-14 00:00:00
abstract:BACKGROUND:Delirium is a common mental disorder with serious adverse outcomes in hospitalised patients. It is associated with increases in mortality, physical morbidity, length of hospital stay, institutionalisation and costs to healthcare providers. A range of risk factors has been implicated in its aetiology, includi...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD005563.pub2
更新日期:2007-04-18 00:00:00
abstract:OBJECTIVES:Postpartum education on contraceptive use is a routine component of discharge planning in many different countries with a wide variety of health care systems. This education is based on assumptions concerning women's receptivity to contraceptive education during the postpartum period and their presumed lack ...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD001863
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Numerous medications are available for the acute treatment of migraine in adults, and some have now been approved for use in children and adolescents in the ambulatory setting. A systematic review of acute treatment of migraine medication trials in children and adolescents will help clinicians make evidence-...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD005220.pub2
更新日期:2016-04-19 00:00:00
abstract:BACKGROUND:Physiological monitoring studies indicate that some preterm infants experience episodes of oxygen desaturation, apnoea, or bradycardia when seated in standard car safety seats. The American Academy of Pediatrics recommends that all preterm infants should be assessed for cardiorespiratory stability in their c...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD005386.pub2
更新日期:2006-01-25 00:00:00
abstract:BACKGROUND:Audit and feedback has been identified as having the potential to change the practice of health care professionals. OBJECTIVES:To assess the effects of audit and feedback on the practice of health professionals and patient outcomes. SEARCH STRATEGY:We searched MEDLINE up to June 1997, the Research and Deve...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD000259
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:5-Aminosalicylates (5-ASA) are considered a first-line therapy for inducing and maintaining remission of mild to moderately active ulcerative colitis (UC). When inflammation in UC is limited to the distal colon, 5-ASA can also be administered rectally as a suppository, enema or foam. OBJECTIVES:A systematic...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD004115.pub2
更新日期:2010-01-20 00:00:00
abstract:BACKGROUND:Lower respiratory tract infections (LRTIs) in young children account for 1.4 million deaths annually worldwide. Antibiotics could be beneficial in preventing LRTIs in high-risk children, and may also help prevent school absenteeism and work days missed by children and/or carers. While it is well documented t...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD011530.pub2
更新日期:2015-09-26 00:00:00
abstract:BACKGROUND:Surgical fixation of fractures of the shaft of the humerus generally involves plating or nailing. It is unclear whether one method is more effective than the other. OBJECTIVES:To compare compression plating and locked intramedullary nailing for primary surgical fixation (surgical fixation of an acute fractu...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD005959.pub2
更新日期:2011-06-15 00:00:00
abstract:BACKGROUND:In areas where vitamin A deficiency (VAD) is a public health concern, the maternal dietary intake of vitamin A may be not sufficient to meet either the maternal nutritional requirements, or those of the breastfed infant, due the low retinol concentrations in breast milk. OBJECTIVES:To evaluate the effects o...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD005944.pub3
更新日期:2016-03-25 00:00:00
abstract:BACKGROUND:Induced abortions are very commonly practiced interventions worldwide. A variety of medical abortion methods have been introduced during the last decade in addition to existing surgical methods. In this review we systematically searched for and combined all evidence from randomised controlled trials comparin...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD003037.pub2
更新日期:2005-01-25 00:00:00
abstract:BACKGROUND:Up to half the people with tuberculosis do not complete their treatment. Thus strategies that improve adherence to treatment regimens are important. OBJECTIVES:To compare policies of directly observed therapy with self treatment at home in people requiring treatment for clinically active tuberculosis, or re...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD003343
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:In response to criticism that epilepsy care for children has little impact, healthcare professionals and administrators have developed various service models and strategies to address perceived inadequacies. OBJECTIVES:To assess the effects of any specialised or dedicated intervention for epilepsy versus us...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD006245.pub4
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND:Diseases caused by Streptococcus pneumoniae (S. pneumoniae) continue to cause substantial morbidity and mortality globally. Whilst pneumococcal polysaccharide vaccines (PPVs) have the potential to prevent disease and death, the degree of protection afforded against various clinical endpoints and within diffe...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD000422.pub3
更新日期:2013-01-31 00:00:00
abstract:BACKGROUND:Surgery remains a mainstay of treatment for malignant tumours; however, surgical manipulation leads to a significant systemic release of tumour cells. Whether these cells lead to metastases is largely dependent on the balance between aggressiveness of the tumour cells and resilience of the body. Surgical str...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD008877.pub2
更新日期:2014-11-07 00:00:00
abstract:BACKGROUND:Operative techniques commonly used for fissure in ano include: anal stretch, open lateral sphincterotomy, closed lateral sphincterotomy, posterior midline sphincterotomy and to a lesser extent dermal flap coverage of the fissure. Reports of direct comparisons between operative techniques for anal fissure are...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD002199.pub2
更新日期:2005-04-18 00:00:00
abstract:BACKGROUND:Research shows that stroke patients and their families are dissatisfied with the information provided and have a poor understanding of stroke and associated issues. OBJECTIVES:To assess the effectiveness of information provision strategies in improving the outcome for stroke patients or their identified car...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD001919.pub3
更新日期:2012-11-14 00:00:00
abstract:BACKGROUND:Autopsy studies suggest that Wernicke-Korsakoff syndrome (WKS) is not a rare disorder, particularly in individuals who abuse alcohol. Thiamine has been established as the treatment of choice for over 50 years, but uncertainty remains about appropriate dosage and duration. Current practice guidelines are base...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD004033.pub3
更新日期:2013-07-01 00:00:00
abstract::This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all integrative therapies compared with treatment as usual/waiting list/attention placebo control conditions for acute depression.To examine the effectiveness and acceptability o...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章
doi:10.1002/14651858.CD008703
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Vaccines against all stages of the malaria parasite are in development, mainly for Plasmodium falciparum, which causes the most serious form of malaria. Pre-erythrocytic vaccines act to prevent or delay a malaria attack by attacking the sporozoite and liver stages before the parasite reaches the bloodstream....
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD006198
更新日期:2006-10-18 00:00:00
abstract:BACKGROUND:The diagnosis of ectopic pregnancy can now often be made by non-invasive methods due to sensitive pregnancy tests (in urine and serum) and high resolution transvaginal sonography, which have been integrated in diagnostic algorithms. These algorithms, in combination with the increased awareness and knowledge ...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD000324
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Diabetes is a chronic illness characterised by insulin resistance or deficiency, resulting in elevated glycosylated haemoglobin A1c (HbA1c) levels. Diet and adherence to dietary advice is associated with lower HbA1c levels and control of disease. Dietary history may be an effective clinical tool for diabetes...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD008488.pub2
更新日期:2011-12-07 00:00:00
abstract:BACKGROUND:Intramedullary nails may be used for the surgical fixation of extracapsular hip fractures in adults. They may be inserted from the top (cephalocondylic) or from the bottom (condylocephalic) end of the femur. OBJECTIVES:To compare different types or design modifications of intramedullary nails used in the fi...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD004961.pub3
更新日期:2006-07-19 00:00:00
abstract:BACKGROUND:Misoprostol is a synthetic prostaglandin which has been used to induce labour. Oral use of the drug misoprostol may be convenient, but an overdose could cause uterine hyperstimulation and precipitate labour which may be life-threatening for both mother and fetus. OBJECTIVES:The objective of this review was ...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD001338
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Adhesions are fibrin bands that are a common consequence of gynaecological surgery. They are caused by various conditions including pelvic inflammatory disease and endometriosis. Adhesions are associated with considerable co-morbidity, including pelvic pain, subfertility and small bowel obstruction. Patients...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD001298.pub4
更新日期:2014-07-09 00:00:00
abstract:BACKGROUND:The Lennox-Gastaut syndrome is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and behaviour disorders. It occurs more frequently in males and onset is usually before the age of eight, with a peak between three and five years. Late...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD003277.pub2
更新日期:2009-07-08 00:00:00
abstract:BACKGROUND:Strategies to implement change in health professional performance have variable impact. A potential explanation is that the barriers to implementation are different in different settings and at different times. Change may be more likely if the strategies were specifically chosen to address the identified bar...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD005470
更新日期:2005-07-20 00:00:00
abstract:BACKGROUND:Total knee arthroplasty (TKA) is a common form of orthopaedic surgery. Venous thromboembolism (VTE), which consists of deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major and potentially fatal complication after TKA. The incidence of DVT after TKA is 40% to 80% and the incidence of PE is app...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD008207.pub3
更新日期:2014-07-29 00:00:00
abstract:BACKGROUND:Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well-tolerated by all people. The aim of this review was to assess whether oxycodone is a...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD003870.pub6
更新日期:2017-08-22 00:00:00