当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > Efficacy outcomes in phase 2 and phase 3 randomized controlled trials in rheumatology.

Efficacy outcomes in phase 2 and phase 3 randomized controlled trials in rheumatology.

Abstract：

:Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthritis. Primary outcomes of American College of Rheumatology (ACR) 20 responses were compared by mixed-model logistic regression, including exploration of potential determinants of efficacy overestimation. In rheumatoid arthritis, phase 2 trial outcomes systematically overestimated subsequent phase 3 results (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.39, 95% confidence interval: 1.25-1.57, P < 0.001). Data for psoriatic arthritis trials were similar, but not statistically significant (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.35, 95% confidence interval: 0.94-1.94, P = 0.09). Differences in inclusion criteria largely explained the observed differences in efficacy findings. Our findings have implications for all stakeholders in new therapeutic development and testing, as well as potential ethical implications.

journal_name

Nat Med

journal_title

Nature medicine

authors

Kerschbaumer A,Smolen JS,Herkner H,Stefanova T,Chwala E,Aletaha D

doi

10.1038/s41591-020-0833-4

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

974-980

issue

6

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-020-0833-4

journal_volume

26

pub_type

杂志文章,meta分析

相关文献

NATURE MEDICINE文献大全
  • On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.

    abstract：:Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threate...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4146

    authors： Theurl I,Hilgendorf I,Nairz M,Tymoszuk P,Haschka D,Asshoff M,He S,Gerhardt LM,Holderried TA,Seifert M,Sopper S,Fenn AM,Anzai A,Rattik S,McAlpine C,Theurl M,Wieghofer P,Iwamoto Y,Weber GF,Harder NK,Chousterman BG,

    更新日期：2016-08-01 00:00:00

  • Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.

    abstract：:Lung cancer is the leading cause of death from cancer in the US and the world. The high mortality rate (80-85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage. Given that cigarette smoke creates a field of injury throughout the airway, we sought to determine i...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1556

    authors： Spira A,Beane JE,Shah V,Steiling K,Liu G,Schembri F,Gilman S,Dumas YM,Calner P,Sebastiani P,Sridhar S,Beamis J,Lamb C,Anderson T,Gerry N,Keane J,Lenburg ME,Brody JS

    更新日期：2007-03-01 00:00:00

  • Mutations in ACTRT1 and its enhancer RNA elements lead to aberrant activation of Hedgehog signaling in inherited and sporadic basal cell carcinomas.

    abstract：:Basal cell carcinoma (BCC), the most common human cancer, results from aberrant activation of the Hedgehog signaling pathway. Although most cases of BCC are sporadic, some forms are inherited, such as Bazex-Dupré-Christol syndrome (BDCS)-a cancer-prone genodermatosis with an X-linked, dominant inheritance pattern. We ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4368

    authors： Bal E,Park HS,Belaid-Choucair Z,Kayserili H,Naville M,Madrange M,Chiticariu E,Hadj-Rabia S,Cagnard N,Kuonen F,Bachmann D,Huber M,Le Gall C,Côté F,Hanein S,Rosti RÖ,Aslanger AD,Waisfisz Q,Bodemer C,Hermine O,Morice

    更新日期：2017-10-01 00:00:00

  • Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations.

    abstract：:Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). A single recessive mutation, the deletion of phenylalanine 508 (deltaF508), causes severe CF and resides on 70% of mutant chromosomes. Severe CF is also caused by premature stop mutations, which are foun...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0496-467

    authors： Howard M,Frizzell RA,Bedwell DM

    更新日期：1996-04-01 00:00:00

  • TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination.

    abstract：:Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by localized areas of demyelination. Although the etiology and pathogenesis of MS remain largely unknown, it is generally assumed that immune responses to myelin antigens contribute to the disease process. The exact se...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0198-078

    authors： Liu J,Marino MW,Wong G,Grail D,Dunn A,Bettadapura J,Slavin AJ,Old L,Bernard CC

    更新日期：1998-01-01 00:00:00

  • HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals.

    abstract：:HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their H...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1197-1250

    authors： Mazzoli S,Trabattoni D,Lo Caputo S,Piconi S,Blé C,Meacci F,Ruzzante S,Salvi A,Semplici F,Longhi R,Fusi ML,Tofani N,Biasin M,Villa ML,Mazzotta F,Clerici M

    更新日期：1997-11-01 00:00:00

  • Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides.

    abstract：:Noninvasive methods are needed to study the kinetic properties of viruses in living organisms. Oncolytic viruses are used increasingly for cancer therapy but there is currently no satisfactory way to measure efficiency of tumor transduction, changing levels of viral gene expression or the timing of virus elimination. ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0502-527

    authors： Peng KW,Facteau S,Wegman T,O'Kane D,Russell SJ

    更新日期：2002-05-01 00:00:00

  • Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway.

    abstract：:LIGHT was recently described as a member of the tumor necrosis factor (TNF) 'superfamily'. We have isolated a mouse homolog of human LIGHT and investigated its immunoregulatory functions in vitro and in vivo. LIGHT has potent, CD28-independent co-stimulatory activity leading to T-cell growth and secretion of gamma int...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/73136

    authors： Tamada K,Shimozaki K,Chapoval AI,Zhu G,Sica G,Flies D,Boone T,Hsu H,Fu YX,Nagata S,Ni J,Chen L

    更新日期：2000-03-01 00:00:00

  • Publisher Correction: Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency.

    abstract：:In the version of this article originally published, there was an error in the legend for Extended Data Fig. 7. The legend for panel f was originally: "f, FACS analysis of IL7R-, CD62L- and CD45RA- expression on TRAC-1928ζ and TRAC-1XX CAR T cells at day 63 post CAR infusion (representative for at least n = 3 mice per...

    journal_title：Nature medicine

    pub_type： 已发布勘误

    doi：10.1038/s41591-019-0360-3

    authors： Feucht J,Sun J,Eyquem J,Ho YJ,Zhao Z,Leibold J,Dobrin A,Cabriolu A,Hamieh M,Sadelain M

    更新日期：2019-03-01 00:00:00

  • Up against the wall.

    abstract：:The notoriously drug-resistant bug MRSA has made headlines for years, but a whole other class of bacteria may prove even more troublesome. These microbes, Gram-negative bacteria, are increasingly a threat--and yet not a single late-stage drug in development specifically targets them. Christian Torres follows one man's...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0610-628

    authors： Torres C

    更新日期：2010-06-01 00:00:00

  • Inhibition of gastric inhibitory polypeptide signaling prevents obesity.

    abstract：:Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with ins...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm727

    authors： Miyawaki K,Yamada Y,Ban N,Ihara Y,Tsukiyama K,Zhou H,Fujimoto S,Oku A,Tsuda K,Toyokuni S,Hiai H,Mizunoya W,Fushiki T,Holst JJ,Makino M,Tashita A,Kobara Y,Tsubamoto Y,Jinnouchi T,Jomori T,Seino Y

    更新日期：2002-07-01 00:00:00

  • PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin.

    abstract：:The N-terminal fragment of prolactin (16K PRL) inhibits tumor growth by impairing angiogenesis, but the underlying mechanisms are unknown. Here, we found that 16K PRL binds the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1), which is known to contextually promote tumor angiogenesis and growth. Loss o...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3552

    authors： Bajou K,Herkenne S,Thijssen VL,D'Amico S,Nguyen NQ,Bouché A,Tabruyn S,Srahna M,Carabin JY,Nivelles O,Paques C,Cornelissen I,Lion M,Noel A,Gils A,Vinckier S,Declerck PJ,Griffioen AW,Dewerchin M,Martial JA,Carmeliet

    更新日期：2014-07-01 00:00:00

  • Identification of a hormonal basis for gallbladder filling.

    abstract：:The cycle of gallbladder filling and emptying controls the flow of bile into the intestine for digestion. Here we show that fibroblast growth factor-15, a hormone made by the distal small intestine in response to bile acids, is required for gallbladder filling. These studies demonstrate that gallbladder filling is act...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1501

    authors： Choi M,Moschetta A,Bookout AL,Peng L,Umetani M,Holmstrom SR,Suino-Powell K,Xu HE,Richardson JA,Gerard RD,Mangelsdorf DJ,Kliewer SA

    更新日期：2006-11-01 00:00:00

  • Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries.

    abstract：:Excitotoxic neuronal damage caused by overactivation of N-methyl-D-aspartate glutamate receptors (NMDARs) is thought to be a principal cause of neuronal loss after stroke and brain trauma. Here we report that activation of sterol regulatory element binding protein-1 (SREBP-1) transcription factor in affected neurons i...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2064

    authors： Taghibiglou C,Martin HG,Lai TW,Cho T,Prasad S,Kojic L,Lu J,Liu Y,Lo E,Zhang S,Wu JZ,Li YP,Wen YH,Imm JH,Cynader MS,Wang YT

    更新日期：2009-12-01 00:00:00

  • A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice.

    abstract：:The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes under...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4311

    authors： Bilkei-Gorzo A,Albayram O,Draffehn A,Michel K,Piyanova A,Oppenheimer H,Dvir-Ginzberg M,Rácz I,Ulas T,Imbeault S,Bab I,Schultze JL,Zimmer A

    更新日期：2017-06-01 00:00:00

  • Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1.

    abstract：:Hereditary hemochromatosis and transfusional iron overload are frequent clinical conditions associated with progressive iron accumulation in parenchymal tissues, leading to eventual organ failure. We have discovered a new mechanism to reverse iron overload-pharmacological modulation of the divalent metal transporter-1...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1542

    authors： Ludwiczek S,Theurl I,Muckenthaler MU,Jakab M,Mair SM,Theurl M,Kiss J,Paulmichl M,Hentze MW,Ritter M,Weiss G

    更新日期：2007-04-01 00:00:00

  • A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1.

    abstract：:Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, for which there is no proven therapy. Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease. The disease begins in utero and is slowly progressive, but it is not known whether cystogenesi...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1675

    authors： Piontek K,Menezes LF,Garcia-Gonzalez MA,Huso DL,Germino GG

    更新日期：2007-12-01 00:00:00

  • Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis.

    abstract：:Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to thera...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4407

    authors： Romero R,Sayin VI,Davidson SM,Bauer MR,Singh SX,LeBoeuf SE,Karakousi TR,Ellis DC,Bhutkar A,Sánchez-Rivera FJ,Subbaraj L,Martinez B,Bronson RT,Prigge JR,Schmidt EE,Thomas CJ,Goparaju C,Davies A,Dolgalev I,Heguy A,A

    更新日期：2017-11-01 00:00:00

  • Targeted estrogen delivery reverses the metabolic syndrome.

    abstract：:We report the development of a new combinatorial approach that allows for peptide-mediated selective tissue targeting of nuclear hormone pharmacology while eliminating adverse effects in other tissues. Specifically, we report the development of a glucagon-like peptide-1 (GLP-1)-estrogen conjugate that has superior sex...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3009

    authors： Finan B,Yang B,Ottaway N,Stemmer K,Müller TD,Yi CX,Habegger K,Schriever SC,García-Cáceres C,Kabra DG,Hembree J,Holland J,Raver C,Seeley RJ,Hans W,Irmler M,Beckers J,de Angelis MH,Tiano JP,Mauvais-Jarvis F,Perez-Ti

    更新日期：2012-12-01 00:00:00

  • Nociceptor sensitization in pain pathogenesis.

    abstract：:The incidence of chronic pain is estimated to be 20-25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of th...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2235

    authors： Gold MS,Gebhart GF

    更新日期：2010-11-01 00:00:00

  • Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial.

    abstract：:Preoperative immunotherapy with anti-PD1 plus anti-CTLA4 antibodies has shown remarkable pathological responses in melanoma1 and colorectal cancer2. In NABUCCO (ClinicalTrials.gov: NCT03387761 ), a single-arm feasibility trial, 24 patients with stage III urothelial cancer (UC) received two doses of ipilimumab and two ...

    journal_title：Nature medicine

    pub_type： 杂志文章,多中心研究

    doi：10.1038/s41591-020-1085-z

    authors： van Dijk N,Gil-Jimenez A,Silina K,Hendricksen K,Smit LA,de Feijter JM,van Montfoort ML,van Rooijen C,Peters D,Broeks A,van der Poel HG,Bruining A,Lubeck Y,Sikorska K,Boellaard TN,Kvistborg P,Vis DJ,Hooijberg E,Schumac

    更新日期：2020-12-01 00:00:00

  • Polygenic architecture informs potential vulnerability to drug-induced liver injury.

    abstract：:Drug-induced liver injury (DILI) is a leading cause of termination in drug development programs and removal of drugs from the market; this is partially due to the inability to identify patients who are at risk1. In this study, we developed a polygenic risk score (PRS) for DILI by aggregating effects of numerous genome...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-1023-0

    authors： Koido M,Kawakami E,Fukumura J,Noguchi Y,Ohori M,Nio Y,Nicoletti P,Aithal GP,Daly AK,Watkins PB,Anayama H,Dragan Y,Shinozawa T,Takebe T

    更新日期：2020-10-01 00:00:00

  • King of hearts: a splicing factor rules cardiac proteins.

    abstract：:Alternative splicing ensures the expression of functionally diverse proteins from individual genes; however, aberrant mRNA splicing is associated with various conditions, including heart disease. A recent study provides new mechanistic insights into heart failure by showing that a human cardiomyopathy-linked mutation ...

    journal_title：Nature medicine

    pub_type： 评论,杂志文章

    doi：10.1038/nm.2762

    authors： Linke WA,Bücker S

    更新日期：2012-05-04 00:00:00

  • Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia.

    abstract：:Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and surviva...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2819

    authors： Kentsis A,Reed C,Rice KL,Sanda T,Rodig SJ,Tholouli E,Christie A,Valk PJ,Delwel R,Ngo V,Kutok JL,Dahlberg SE,Moreau LA,Byers RJ,Christensen JG,Vande Woude G,Licht JD,Kung AL,Staudt LM,Look AT

    更新日期：2012-07-01 00:00:00

  • Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease.

    abstract：:Huntington's disease (HD) is a fatal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal neurodegeneration in HD. The mec...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3514

    authors： Wang N,Gray M,Lu XH,Cantle JP,Holley SM,Greiner E,Gu X,Shirasaki D,Cepeda C,Li Y,Dong H,Levine MS,Yang XW

    更新日期：2014-05-01 00:00:00

  • A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells.

    abstract：:Cellular immunity has an inherent high level of functional heterogeneity. Capturing the full spectrum of these functions requires analysis of large numbers of effector molecules from single cells. We report a microfluidic platform designed for highly multiplexed (more than ten proteins), reliable, sample-efficient (∼1...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2375

    authors： Ma C,Fan R,Ahmad H,Shi Q,Comin-Anduix B,Chodon T,Koya RC,Liu CC,Kwong GA,Radu CG,Ribas A,Heath JR

    更新日期：2011-06-01 00:00:00

  • Under pressure: the search for the essential mechanisms of hypertension.

    abstract：:High blood pressure, or hypertension, is a very common disorder with a substantial impact on public health because of its associated complications. Despite the high prevalence of essential hypertension and years of research, the basic causes remain obscure. Here I review recent advances in understanding the pathophysi...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/nm.2541

    authors： Coffman TM

    更新日期：2011-11-07 00:00:00

  • A negative regulator of MAP kinase causes depressive behavior.

    abstract：:The lifetime prevalence (∼16%) and the economic burden ($100 billion annually) associated with major depressive disorder (MDD) make it one of the most common and debilitating neurobiological illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology of MDD have not been identified. ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2219

    authors： Duric V,Banasr M,Licznerski P,Schmidt HD,Stockmeier CA,Simen AA,Newton SS,Duman RS

    更新日期：2010-11-01 00:00:00

  • Molecular foundations of cancer: new targets for intervention.

    abstract：:Conceptual and practical advances in molecular medicine are changing our understanding of cancer pathogenesis. In time this should provide the opportunity to alter the natural history of many cancers. ...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/nm0495-309

    authors： Karp JE,Broder S

    更新日期：1995-04-01 00:00:00

  • Mechanisms of NAFLD development and therapeutic strategies.

    abstract：:There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosi...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/s41591-018-0104-9

    authors： Friedman SL,Neuschwander-Tetri BA,Rinella M,Sanyal AJ

    更新日期：2018-07-01 00:00:00