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10.1136/gutjnl-2011-301668 http://scihub22266oqcxt.onion/10.1136/gutjnl-2011-301668 C4902107!4902107 !22595313     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=22595313 &cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\22595313 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Gut 2012 ; 61 (12 ): 1693-700 Nephropedia Template TP {{tp|p=22595313 |t=2012. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn s disease: unexpected results of a randomised, double-blind placebo-controlled trial |pdf=|usr=}}{{22595313 }} gab.com Text Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn s disease: unexpected results of a randomised, double-blind placebo-controlled trial JO: Gut http://www.kidney.de/pget.php?&tw=1&pmid=22595313 #FOAvip OBJECTIVE: The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn's disease. DESIGN: In a double-blind, randomised, placebo-controlled proof-of-concept study, 59 patients with moderate to severe Crohn's disease (Crohn's Disease Activity Index (CDAI) ?220 to ?450) were assigned in a 2:1 ratio to 2×10 mg/kg intravenous secukinumab or placebo. The primary end point, addressed by bayesian statistics augmented with historical placebo information, was the probability that secukinumab reduces the CDAI by ?50 points more than placebo at week 6. Ancillary analyses explored associations of 35 candidate genetic polymorphisms and faecal calprotectin response. RESULTS: 59 patients (39 secukinumab, 20 placebo, mean baseline CDAI 307 and 301, respectively) were recruited. 18/59 (31%) patients discontinued prematurely (12/39 (31%) secukinumab, 6/20 (30%) placebo), 10/59 (17%) due to insufficient therapeutic effect (8/39 (21%) secukinumab, 2/20 (10%) placebo). Fourteen serious adverse events occurred in 10 patients (seven secukinumab, three placebo); 20 infections, including four local fungal infections, were seen on secukinumab versus none on placebo. Primary end point analysis estimated <0.1% probability (CDAI (SD) =33.9 (19.7), 95% credible interval -4.9 to 72.9) that secukinumab reduces CDAI by ?50 points more than placebo. Secondary area under the curve analysis (weeks 4-10) showed a significant difference (mean ?CDAI=49; 95% CI (2 to 96), p=0.043) in favour of placebo. Post hoc subgroup analysis showed that unfavourable responses on secukinumab were driven by patients with elevated inflammatory markers (CRP?10 mg/l and/or faecal calprotectin?200 ng/ml; mean ?CDAI=62; 95% CI (-1 to 125), p=0.054 in favour of placebo). Absence of the minor allele of tumour necrosis factor-like ligand 1A was strongly associated with lack of response measured by baseline-adjusted changes in calprotectin at week 6 (p=0.00035 Bonferroni-corrected). CONCLUSIONS: Blockade of IL-17A was ineffective and higher rates of adverse events were noted compared with placebo. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrial.gov with the number NCT01009281. Twit Text FOAVip Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn s disease: unexpected results of a randomised, double-blind placebo-controlled trial ????Gut http://www.kidney.de/pget.php?&tw=1&pmid=22595313 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=22595313 #FOAvip English Wikipedia <ref>{{Cite pmid|22595313 }}</ref> Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn s disease: unexpected results of a randomised, double-blind placebo-controlled trial #MMPMID22595313 Hueber W ; Sands BE ; Lewitzky S ; Vandemeulebroecke M ; Reinisch W ; Higgins PD ; Wehkamp J ; Feagan BG ; Yao MD ; Karczewski M ; Karczewski J ; Pezous N ; Bek S ; Bruin G ; Mellgard B ; Berger C ; Londei M ; Bertolino AP ; Tougas G ; Travis SP Gut 2012[Dec]; 61 (12 ): 1693-700 PMID22595313 show ga OBJECTIVE: The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn's disease. DESIGN: In a double-blind, randomised, placebo-controlled proof-of-concept study, 59 patients with moderate to severe Crohn's disease (Crohn's Disease Activity Index (CDAI) ?220 to ?450) were assigned in a 2:1 ratio to 2×10 mg/kg intravenous secukinumab or placebo. The primary end point, addressed by bayesian statistics augmented with historical placebo information, was the probability that secukinumab reduces the CDAI by ?50 points more than placebo at week 6. Ancillary analyses explored associations of 35 candidate genetic polymorphisms and faecal calprotectin response. RESULTS: 59 patients (39 secukinumab, 20 placebo, mean baseline CDAI 307 and 301, respectively) were recruited. 18/59 (31%) patients discontinued prematurely (12/39 (31%) secukinumab, 6/20 (30%) placebo), 10/59 (17%) due to insufficient therapeutic effect (8/39 (21%) secukinumab, 2/20 (10%) placebo). Fourteen serious adverse events occurred in 10 patients (seven secukinumab, three placebo); 20 infections, including four local fungal infections, were seen on secukinumab versus none on placebo. Primary end point analysis estimated <0.1% probability (CDAI (SD) =33.9 (19.7), 95% credible interval -4.9 to 72.9) that secukinumab reduces CDAI by ?50 points more than placebo. Secondary area under the curve analysis (weeks 4-10) showed a significant difference (mean ?CDAI=49; 95% CI (2 to 96), p=0.043) in favour of placebo. Post hoc subgroup analysis showed that unfavourable responses on secukinumab were driven by patients with elevated inflammatory markers (CRP?10 mg/l and/or faecal calprotectin?200 ng/ml; mean ?CDAI=62; 95% CI (-1 to 125), p=0.054 in favour of placebo). Absence of the minor allele of tumour necrosis factor-like ligand 1A was strongly associated with lack of response measured by baseline-adjusted changes in calprotectin at week 6 (p=0.00035 Bonferroni-corrected). CONCLUSIONS: Blockade of IL-17A was ineffective and higher rates of adverse events were noted compared with placebo. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrial.gov with the number NCT01009281. |Adolescent [MESH] |Adult [MESH] |Aged [MESH] |Anti-Inflammatory Agents/*therapeutic use [MESH] |Antibodies, Monoclonal, Humanized [MESH] |Antibodies, Monoclonal/*therapeutic use [MESH] |Bayes Theorem [MESH] |Biomarkers/metabolism [MESH] |Crohn Disease/*drug therapy/genetics [MESH] |Double-Blind Method [MESH] |Drug Administration Schedule [MESH] |Female [MESH] |Genetic Markers [MESH] |Humans [MESH] |Infusions, Intravenous [MESH] |Interleukin-17/antagonists & inhibitors/genetics [MESH] |Leukocyte L1 Antigen Complex/metabolism [MESH] |Male [MESH] |Middle Aged [MESH] |Polymorphism, Single Nucleotide [MESH] |Severity of Illness Index [MESH] |Treatment Failure [MESH]Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to (epmc).pdf DeepDyve Pubget Overpricing