%PDF-1.7
%
1 0 obj
<>>>
endobj
2 0 obj
<>stream
2017-03-08T11:13:12-05:00
2017-03-08T11:13:38-05:00
2017-03-08T11:13:38-05:00
Adobe InDesign CC 2017 (Windows)
uuid:cac30b78-a1dd-409a-9de9-fff50b4670cd
xmp.did:4A42F9656056E111960DCE8E95F0DF9D
xmp.id:1ef644a0-3462-e84b-9694-895ca9eb71e2
proof:pdf
xmp.iid:cf57fbfa-2aa6-ec40-a12b-7f903e9e3e7b
xmp.did:3f01e3da-4bd9-874c-903b-cc44f94c5fb3
xmp.did:4A42F9656056E111960DCE8E95F0DF9D
default
converted
from application/x-indesign to application/pdf
Adobe InDesign CC 2017 (Windows)
/
2017-03-08T11:13:13-05:00
application/pdf
Adobe PDF Library 15.0
False
endstream
endobj
3 0 obj
<>
endobj
5 0 obj
<>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/TrimBox[0.0 0.0 612.0 792.0]/Type/Page>>
endobj
6 0 obj
<>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC/ImageI]/XObject<>>>/TrimBox[0.0 0.0 612.0 792.0]/Type/Page>>
endobj
17 0 obj
<>stream
BT
0 0 0 1 k
/GS0 gs
/TT0 1 Tf
7 0 0 7 60.48 22.6817 Tm
(2 )Tj
/Span<>> BDC
( )Tj
EMC
59.297 0 Td
[(Pharmacology W)54.6 (atch)]TJ
4.081 0 0 4.081 535.1605 25.0127 Tm
(\256)Tj
ET
q
0 g
/GS1 gs
0 TL/Fm0 Do
Q
BT
/T1_0 1 Tf
-0.01 Tc 7 0 0 7 40.75 257.75 Tm
(PHARMACOLOGY WATCH)Tj
/T1_1 1 Tf
6 0 0 6 127.892 257.75 Tm
[(\231 is published monthly by AHC Media, a Relias Learning)-10 ( )]TJ
-14.524 -1.167 Td
(company. Copyright \251 2017 AHC Media, a Relias Learning company.)Tj
/T1_2 1 Tf
0.01 Tw 8 0 0 8 40.75 240.75 Tm
(Author)Tj
/T1_1 1 Tf
(: )Tj
/T1_3 1 Tf
0 Tw 3.698 0 Td
(William T. Elliott, MD, FACP, )Tj
/T1_1 1 Tf
[(Assistant Clinical Professor of)-10 ( )]TJ
-3.698 -1.25 Td
(Medicine, University of California, San Francisco)Tj
/T1_2 1 Tf
0.01 Tw 0 -1.25 TD
(Editor:)Tj
/T1_1 1 Tf
0 Tw ( Jonathan Springston)Tj
/T1_2 1 Tf
T*
(Executive Editor:)Tj
/T1_1 1 Tf
( Leslie Coplin)Tj
6 0 0 6 40.75 199.25 Tm
[(This is an educational publication designed to present scientific inform\
ation and opinion to)-10 ( )]TJ
0 -1.167 TD
[(health professionals, stimulate thought, and further investigation. It d\
oes not provide advice)-10 ( )]TJ
0 -1.167 TD
[(regarding medical diagnosis or treatment for any individual case. It is \
not intended for the)-10 ( )]TJ
0.01 Tw 0 -1.167 TD
(layman.)Tj
0.01 Tc 0 Tw 0 -1.917 TD
(STATEMENT OF FINANCIAL DISCLOSURE)Tj
-0.01 Tc 0 -1.167 TD
[(To reveal any potential bias in this publication, and in accordance with\
Accreditation Council)-9.9 ( )]TJ
0 -1.167 TD
[(for Continuing Medical Education guidelines, Dr. Elliott, Ms. Coplin, an\
d Mr. Springston)-10 ( )]TJ
T*
(report no financial relationships relevant to this field of study.)Tj
ET
/CS0 CS 1 SCN
0.25 w 4 M
/GS1 gs
36.125 45.125 251.75 222.5 re
S
/CS0 cs 0.1 scn
122.4 50.76 160.85 69.12 re
f
0.86 0.57 0 0.16 K
0.3 w 10 M
q 1 0 0 1 167.2314 90.3042 cm
0 0 m
81.287 0 l
S
Q
q 1 0 0 1 151.4756 83.3042 cm
0 0 m
42.017 0 l
S
Q
BT
0 0 0 1 k
/GS0 gs
/T1_2 1 Tf
0.05 Tc 8 0 0 8 126.9 108.1801 Tm
[(SUBSCRIBER INFORMA)92 (TION)]TJ
-0.01 Tc 7 0 0 7 126.9 97.9041 Tm
(Customer Service: \(800\) 688-2421)Tj
/T1_1 1 Tf
6 0 0 6 126.9 90.9041 Tm
(Email Address: )Tj
0.86 0.57 0 0.16 k
/GS1 gs
0.01 Tw (jspringston@reliaslearning.com)Tj
0 0 0 1 k
/GS0 gs
T*
(Website: )Tj
0.86 0.57 0 0.16 k
/GS1 gs
4.096 0 Td
(AHCMedia.com)Tj
0 0 0 1 k
/GS0 gs
0 Tw -4.096 -1.917 Td
[(Address Correspondence to: AHC Media, a Relias)-10 ( )]TJ
T*
(Learning company, 111 Corning Road, Suite 250)Tj
0 Tc 20.859 0 Td
( )Tj
-0.01 Tc -20.859 -1.167 Td
(Cary, NC 27518)Tj
ET
q
44.685 105.861 69.075 -38.181 re
W n
q
/GS1 gs
69.0754403 0 0 38.181203 44.6845703 67.6800183 cm
/Im0 Do
Q
Q
BT
/T1_4 1 Tf
-0.03 Tc 10 0 0 10 36 745.2775 Tm
[(hematoma, and the highest odds of subdural hematoma was)-30 ( )]TJ
0 -1.2 TD
[(associated with combined use of a VKA and an antiplatelet)-30 ( )]TJ
T*
(drug \()Tj
/T1_5 1 Tf
0.03 Tw (JAMA)Tj
/T1_4 1 Tf
0 Tw [( 2017;317:836-846\). This study suggests that the)-30 ( )]TJ
T*
[(newer direct oral anticoagulants may be safer in this regard)-30 ( )]TJ
T*
[(than warfarin therapy)92 (.)]TJ
/TT0 1 Tf
0 Tc 14 0 0 14 36 669.2775 Tm
[(P)35.7 (opular Drug Could Help P)17.6 (revent T)175.9 (ype 2 )]TJ
0 -1.143 TD
(Diabetes)Tj
/T1_4 1 Tf
-0.03 Tc 10 0 0 10 36 641.2775 Tm
(Does liraglutide play a role in the prevention of type 2 diabe)Tj
0 Tc (-)Tj
-0.03 Tc 0 -1.2 TD
(tes? A new industry-sponsored study examined 2,254 individ)Tj
0 Tc (-)Tj
-0.03 Tc T*
[(uals who presented with prediabetes to evaluate liraglutide\222)74 (s)-30 ( )]TJ
T*
[(effect on the progression to type 2 diabetes. Subjects were)-29.9 ( )]TJ
T*
[(randomized 2:1 to liraglutide 3 mg subcutaneous injection)-30 ( )]TJ
T*
(once daily or placebo. Both groups also received reduced calo)Tj
0 Tc (-)Tj
-0.03 Tc T*
[(rie diets and counseling on exercise. A little more than 50%)-30 ( )]TJ
T*
[(of the study group dropped out during the three-year test)-30 ( )]TJ
T*
[(period. At week 160, 2% of the liraglutide group vs. 6% of)-30 ( )]TJ
T*
[(the placebo group were diagnosed with diabetes. Liraglutide)-30 ( )]TJ
T*
[(induced greater weight loss than placebo at week 160 \(-6.1%)-30 ( )]TJ
T*
[([standard deviation, 7.3] vs. -1.9% [standard deviation, 6.3];)-30 ( )]TJ
T*
[(estimated treatment difference, -4.3%; 95% CI, -4.9 to -3.7;)-30 ( )]TJ
/T1_5 1 Tf
0 Tc T*
(P)Tj
/T1_4 1 Tf
-0.03 Tc 0.581 0 Td
[( < 0.0001\). Adverse events occurred at about the same rate)-30 ( )]TJ
-0.581 -1.2 Td
[(in both groups. The authors concluded \223... with the limitation)-30 ( )]TJ
T*
(that withdrawn individuals were not followed up after discon)Tj
0 Tc (-)Tj
-0.03 Tc T*
[(tinuation, liraglutide 3.0 mg might provide health bene\037ts in)-30 ( )]TJ
T*
[(terms of reduced risk of diabetes in individuals with obesity)-30 ( )]TJ
T*
(and prediabetes.\224 \()Tj
/T1_5 1 Tf
0.03 Tw (Lancet)Tj
/T1_4 1 Tf
0 Tw [(. Published online Feb. 22, 2017.)-30 ( )]TJ
T*
(doi: http://dx.doi.org/10.1016/S0140-6736\(17\)30069-7\))Tj
/TT0 1 Tf
0 Tc 14 0 0 14 36 385.2775 Tm
(Breakthrough in Rheumatoid Arthritis )Tj
15.436 0 Td
( )Tj
-15.436 -1.143 Td
[(T)175 (reatment?)]TJ
/T1_4 1 Tf
-0.03 Tc 10 0 0 10 36 357.2775 Tm
(Baricitinib is an oral JAK1 and JAK2 inhibitor under inves)Tj
0 Tc (-)Tj
-0.03 Tc T*
[(tigation in rheumatoid arthritis \(RA\) subjects. In a 52-week)-30 ( )]TJ
T*
[(Phase III trial, 1,307 patients suffering from RA who were)-30 ( )]TJ
T*
[(taking methotrexate were randomized to baricitinib, placebo,)-30 ( )]TJ
T*
[(or the TNF inhibitor adalimumab \(Humira\). Disease activity)-30 ( )]TJ
T*
[(was measured on several standard RA disease activity scales.)-30 ( )]TJ
T*
(Baricitinib was superior to placebo in all measures \()Tj
/T1_5 1 Tf
0 Tc (P)Tj
/T1_4 1 Tf
-0.03 Tc 21.329 0 Td
[( > 0.001\))-30 ( )]TJ
-21.329 -1.2 Td
[(and outperformed adalimumab in the American College)-30 ( )]TJ
27 47.2 Td
(of Rheumatology criteria at 12 weeks \(70% vs. 61%; )Tj
/T1_5 1 Tf
0 Tc (P)Tj
/T1_4 1 Tf
-0.03 Tw 22.388 0 Td
( = )Tj
-0.03 Tc 0 Tw -22.388 -1.2 Td
[(0.014\). Infections were more common with baricitinib. The)-30 ( )]TJ
T*
[(authors concluded baricitinib was associated with signi\037cant)-30 ( )]TJ
T*
(clinical improvements as compared with placebo and adalim)Tj
0 Tc (-)Tj
-0.03 Tc T*
(umab. \()Tj
/T1_5 1 Tf
(N Engl J Med)Tj
/T1_4 1 Tf
( 2017;376:652-662\))Tj
/TT0 1 Tf
0 Tc 14 0 0 14 306 669.2775 Tm
[(Comparing T)175.2 (reatments for Atopic )]TJ
13.869 0 Td
( )Tj
-13.869 -1.143 Td
(Dermatitis)Tj
/T1_4 1 Tf
-0.03 Tc 10 0 0 10 306 641.2775 Tm
[(A new interleukin-31 inhibitor is under evaluation for the)-29.9 ( )]TJ
T*
[(treatment of atopic dermatitis. Nemolizumab was compared)-30 ( )]TJ
T*
(to placebo in a 12-week trial in 216 adults with moderate-to-)Tj
T*
[(severe atopic dermatitis that was inadequately controlled by)-30 ( )]TJ
T*
[(topical treatments. Three different dose ranges of the active)-30 ( )]TJ
T*
[(drug were administered subcutaneously every four weeks,)-30 ( )]TJ
T*
[(along with placebo. Nemolizumab performed signi\037cantly)-30 ( )]TJ
T*
[(better than placebo in the pruritus visual-analogue scale for all)-30 ( )]TJ
T*
[(three dose ranges, with increasing ef\037cacy with higher dosing)-30 ( )]TJ
0 Tc T*
(\()Tj
/T1_5 1 Tf
0.303 0 Td
(P)Tj
/T1_4 1 Tf
-0.03 Tc 0.581 0 Td
( > 0.01 for all comparisons\). For all measures, the interme)Tj
0 Tc (-)Tj
-0.03 Tc -0.884 -1.2 Td
[(diate dose \(0.5 mg/kg every four weeks\) demonstrated the best)-30 ( )]TJ
T*
[(bene\037t-risk pro\037le. The authors concluded that nemolizumab)-30 ( )]TJ
T*
[(reduced pruritus in patients suffering from moderate-to-severe)-30 ( )]TJ
T*
(atopic dermatitis \()Tj
/T1_5 1 Tf
(N Engl J Med)Tj
/T1_4 1 Tf
[( 2017;376:826-835\). This)-29.9 ( )]TJ
T*
(study was sponsored by Chugai Pharmaceutical.)Tj
/TT0 1 Tf
0 Tc 14 0 0 14 306 445.2775 Tm
[(A P)35.6 (ossible New Hope for Leukemia P)36.8 (atients)]TJ
/T1_4 1 Tf
-0.03 Tc 10 0 0 10 306 433.2775 Tm
(Blinatumomab, a new agent designed to treat acute lym)Tj
0 Tc (-)Tj
-0.03 Tc T*
[(phoblastic leukemia, is in Phase III trials. The drug enables)-30 ( )]TJ
T*
[(CD3-positive T cells to recognize and eliminate CD19-positive)-29.9 ( )]TJ
T*
[(acute lymphoblastic leukemia \(ALL\) blasts. A new study)-30 ( )]TJ
T*
(assigned 405 adults with heavily pretreated B-cell precur)Tj
0 Tc 22.628 0 Td
(-)Tj
-0.03 Tc -22.628 -1.2 Td
[(sor ALL, in a 2:1 ratio, to receive either blinatumomab or)-30 ( )]TJ
T*
[(standard-of-care chemotherapy)92 (. The median overall survival)-30 ( )]TJ
T*
[(was 7.7 months in the blinatumomab group and 4.0 months)-30 ( )]TJ
T*
[(in the chemotherapy group \(hazard ratio for death with)-30 ( )]TJ
T*
[(blinatumomab vs. chemotherapy)92.1 (, 0.71; 95% CI, 0.55-0.93;)-30 ( )]TJ
/T1_5 1 Tf
0 Tc T*
(P)Tj
/T1_4 1 Tf
-0.03 Tc 0.581 0 Td
[( = 0.01\). Along with improved survival, remission rates and)-30 ( )]TJ
-0.581 -1.2 Td
(event-free survival were signi\037cantly higher in the blinatu)Tj
0 Tc (-)Tj
-0.03 Tc T*
[(momab group. About one-quarter of both treatment groups)-30 ( )]TJ
T*
[(underwent allogeneic stem cell transplantation. Adverse events)-30 ( )]TJ
T*
[(were lower with blinatumomab. T)67.1 (reatment with blinatu)]TJ
0 Tc (-)Tj
-0.03 Tc T*
[(momab resulted in signi\037cantly longer overall survival than)-30 ( )]TJ
T*
(chemotherapy among adult patients with relapsed or refrac)Tj
0 Tc (-)Tj
-0.03 Tc T*
(tory B-cell precursor ALL. \()Tj
/T1_5 1 Tf
(N Engl J Med)Tj
/T1_4 1 Tf
( 2017;376:836-847\))Tj
/TT0 1 Tf
0 Tc 14 0 0 14 306 201.2775 Tm
[(FD)17.4 (A Action)]TJ
/T1_4 1 Tf
-0.03 Tc 10 0 0 10 306 189.2775 Tm
[(The FDA has approved brodalumab to treat adults with)-30 ( )]TJ
T*
[(moderate-to-severe plaque psoriasis. The drug, which is)-30 ( )]TJ
T*
[(administered as a subcutaneous injection, binds the IL-17)-30 ( )]TJ
T*
[(receptor)111 (. It was approved on the strength of three randomized,)-30 ( )]TJ
T*
[(placebo-controlled, clinical trials that contained nearly 4,400)-30 ( )]TJ
T*
(adults who are candidates for systemic therapy or photother)Tj
0 Tc 24.179 0 Td
(-)Tj
-0.03 Tc -24.179 -1.2 Td
[(apy)92 (. More patients treated with brodalumab exhibited skin)-30 ( )]TJ
T*
[(that was clear or almost clear compared to placebo. Suicidal)-30 ( )]TJ
T*
[(ideation and behavior occurred at a higher rate during clinical)-30 ( )]TJ
T*
[(trials and delayed approval of the drug. Eventually)92 (, it was ap)]TJ
0 Tc (-)Tj
-0.03 Tc T*
(proved with a boxed warning and is only available to restrict)Tj
0 Tc (-)Tj
-0.03 Tc T*
[(ed program under a Risk Evaluation and Mitigation Strategy)92 (.)-30 ( )]TJ
T*
(Brodalumab is marketed as Siliq. )Tj
/CS0 cs 1 scn
/GS1 gs
/C2_0 1 Tf
0 Tc <0084>Tj
ET
endstream
endobj
18 0 obj
<>
endobj
25 0 obj
<>>>/Subtype/Form>>stream
0 0 0 1 K
3 w 4 M 0 j 0 J
/GS0 gs
q 1 0 0 1 18 764.5 cm
0 0 m
558 0 l
S
Q
endstream
endobj
26 0 obj
<>stream
Ho\L4JEP(V
1ƁT _0/jiR^b[XUUkl6K+ņļ; %_bMlw{{/{w{j_ѻ}=};ϼ}fD+{mOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]1tOW?]=/:6A.>%"'#0T1~UopD(=2,MdϞXWPso@;Eגg^ՀC6,
ΡN OxuK;^t
[j=PmNC7yghTS[5?{}$KX`^Y*/ҧFbBu{sQxiԱX;H+"nMo9W|I >\ /Bd)zgwLXKg/OY2-Ipe.X5#Bmp^ /cČkF:qɈJ^(#V6;^I(INtдd17Sʼn.wsʝ)X|vF|\N3_XWNANJ^P;ǝaۆzO;?HTX%{HIK=Һ*:6*W-h`(gE٫a;Y
QcD}ա"+ɡm,ړ<{5|=LHݪDqOh]Ζ\-bPHʮC=}6QtCT'@p ߋddK͝pK`lBE#NS$ä7
Y˿Q&(;p3C$o@}9}97Ft&>DHQ,>m饸Cx~Inqj?/stTX.=a<s8峸U<)Ӕ_nmGig{ {.\O/gUyY>r:JX=
my٭oܧM.-l[
_}၁6wRrp`ƹc hC!{ޞC/AP9k5vFAݸl 0a./,Az;c9o$))gO7:Zs E.e%qn\#YWfTsǯzBe)}foR\y31Μϫ(qgSünq
{Y%e섈>ps ^~/q'}rʲ1BV~䓑_h\LV\nѹJ\h_Huq/Bj'Wl
=BN14WAehrRynSb'qmOm7_͛89uRQFȂ"KDJʲ8^A*ʡ|bZp Ǔ>
zc$~7տugJjS.0V}+=SwQ)*V\'t*-.<Ԝ'sr?V獃MO4ϧ==g
\$U/-WX$ije'ŧ8o!88ڂlW"8H6
*}[syI oZZⰿOਓ
~y)x?lkZZ_ҏ\(}H
<\q,>TkVnCC1\B?D*o[UD럪gb=bq
>D/tq\\25bB$FGks%cDQm
m 8xqXg1HC?ϣA>q}x#dv]
A-~_7" 1tQK確#nO ügҵFEytkݿN xlluxg]C):3Jo<>Inq93h\(~\uB-6@
U]sKt
}>t.v?0uxHx"7D g,Fl|^L^-LqC^,>Ã/*AXm~4pQMs~OWӷTw8"c$,Z8k
́ i.x\>ko|hft+2܅Ͼ釓?jmrq۹fk4~w+cԣC-2zjSk,wO8cXފpD"N.A
BJڡa'lOo8w{6`er@FOmdTe?+gZCR>2s0Bdu
9䮽:;E1Fg#gxEǟ{&BfV 5=w 'χ]{j.ˋ#96-7貄$rȦcDFVn¿?M묟5|g*GM@ ȅ?8pa譕pksVk A$)#.+ƍ?/m<|߁NqA.QI\Z&Oqԏy=cfaY)_OILT[W+_s:G@4A
i.+GAU~Ӹef/~/(3ML>0B!A4uWJ6I1MCLO-Ei0mS%$m91P\68fgn^iC˝i2M5_Y<>ğ<.37T1Zɩ/G!:X,؟