Journal Reading - Edi

8/18/2019 Journal Reading - Edi

1/21

Iain C. Macdougall, M.D. et alN Engl J Med 2013;368:320-32.

DOI: 10.1056/NEJMoa1203166

Peginesatide for Anemia in Patients withChronic Kidney Disease Not Receiving

Dialysis

JOURNAL READIN

leh!

Ed! "#$na%an& '."edNIM.I11110013

Ke"aniteraan Klini# Mayor

$tase Ilmu Penya#it Dalam

R'UD '#l(an ')a$!e* M#+a,,ad Alad$!e

on(!ana 2016

%


2/21

&ac#groundeg!nea(!de is a "e"tide 'ased

erythro"oiesis stimulating agent ()$A* thatmay have thera"eutic "otential for anemiain "atients with advanced chronic #idney

diseaseA!, o* (#d)! )valuated the safety and

ecacy of "eginesatide, as com"ared withanother )$A, da$eoe(!n& in +- such"atients who were not undergoing dialysis


3/21


4/21

Methods Inl#!on: Patients with chronic #idney

disease were % yo or older )stimated ;


5/21

$tudy )nd Points /he primary ecacy end "oint was the

,ean +ange from the 'aseline hemoglo'inlevel to the mean level during the evaluation"eriod

Secondary ecacy end "oints were the"ro"ortion of "atients receiving a transfusionand the "ro"ortion of "atients in whom therewas a res"onse in hemoglo'in levels

Cardiovascular safety was evaluated on the'asis of an ad8udicated com"osite end "oint.

4


6/21

=


7/21

6


8/21

Results4+e ,ean 'D7 +ange from the 'aseline

hemoglo'in levels to the mean level during the% wee# evaluation "eriod!$o# EARL 1 EARL 2

lower starting dose of

"eginesatide

%.-+B3.6 g:dl %.43B3.+3 g:dl

higher starting dose of"eginesatide

%.=5B3.+6 g:dl %.=B3.+= g:dl

dar'e"oetin %.-6B3.= g:dl %.-4B%.33 g:dl• Mean +e,oglo!n leel were increased and

maintained at "oints within the target range inall grou"s in 'oth studies (


9/21

+


10/21

%3


11/21

%%


12/21

Com"osite $afety )nd Pointevents contri'uting to the com"osite safety

end "oint occurred in %5% of =4= "atientsreceiving "eginesatide (%.4* and 4= of-6 "atients receiving dar'e"oetin (%6.%*

/he ha0ard ratio with "eginesatide relativeto dar'e"oetin was %.- with numericallyhigher event rates with "eginesatide thanwith dar'e"oetin in three categories! death(. vs. =.6*, unsta'le angina (.5 vs.3.+*, and arrhythmia (4.= vs. 5.3*

%


13/21

%-


14/21

Ade$e Een( /he "ro"ortion of "atients who re"orted adverse

events was similar in the "eginesatide grou"scom'ined (+-.=* and in the dar'e"oetin grou"(+%.5*. /here were no ma8or dierences

/here were no l!n!all) $elean( d!9e$enein the incidence of adverse events #nown to 'erelated to the )$A class of drugs.

Changes from 'aseline in 'lood "ressure %e$e!,!la$ in the "eginesatide and dar'e"oetin

grou"s and (+e$e %e$e no l!n!all) $elean('etween grou" dierences in the intensicationof antihy"ertensive medications

%5


15/21

Ade$e Een($erious adverse events were re"orted ,o$e

*$e#en(l) with "eginesatide (5.4* thanwith dar'e"oetin (5-.%*.

!g+e$ !n!dene of acute renal failure

(.4 vs. 5.-* and anemia (-.4 vs. %.4*were o'served with "eginesatide than withdar'e"oetin.

Mean changes in the results of renal function

tests and in the Pro"ortion of "atients with"rogression to dialysis or to stage 4 CKD%e$e !,!la$ with the two study drugs.

%4


16/21

%=


17/21

Discussions

In this com"arison of two )$As in "atientsnot receiving dialysis, an increase incom"osite safety end "oint events,including sudden death, was o'served with

"eginesatide.Regarding the dierence in the rate of

sudden death 'etween the "eginesatideand dar'e"oetin grou"s, no clinically

relevant 'etween grou" dierences wereo'served in "otassium levels or "lateletcounts.

%6


18/21

Although the "atho"hysiology of sudden death in"atients with chronic #idney disease is oftenattri'uta'le to ventricular arrhythmia "reci"itated'y myocardial infarction, there were no a""arent'etween grou" dierences in ad8udicated cases of

myocardial infarction, congestive heart failure, orinvestigator re"orted ventricular arrhythmias.

/his nding is consistent with studies in mon#eysshowing no evidence of a "roarrhythmic "otentialwith "eginesatide.

$imilarly, there were no clinically relevant 'etweengrou" dierences in 'lood "ressure, hy"ertensionrelated events, or venous throm'oem'olism

%


19/21

Potential limitations of the P)AR1 studiesinclude the o"en la'el design, which couldhave 'iased the assessment of the EsofterFend "oints (arrhythmia, congestive heart

failure, and unsta'le angina* /he study "o"ulation of "atients not

receiving dialysis, in P)AR1 % and wassmaller. /he smaller study "o"ulation and

the randomi0ation of may have contri'utedto the challenges of achieving 'alancedgrou"s at 'aseline.

%+


20/21

Conclusions

In conclusion, although thus studiesshowed that monthly administration of"eginesatide was as eective asadministration of dar'e"oetin every

wee#s in increasing and maintaininghemoglo'in levels in "atients with chronic#idney disease who were not receivingdialysis, there was an increase in

cardiovascular events and deaths with"eginesatide that was une?"ected andremains une?"lained.

3


21/21

/han# Gou

%

Documents

Journal Reading - Edi