%PDF-1.4
%
71 0 obj
<>
endobj
68 0 obj
<>
endobj
144 0 obj
<>stream
Acrobat Distiller 4.05 for Macintosh
2004-04-30T07:56:31Z
2024-03-29T01:48:44-07:00
QuarkXPressª 4.11: AdobePS 8.8.0 (301)
2024-03-29T01:48:44-07:00
application/pdf
Heather
2004-15.may.suppl 71
uuid:bf378640-1dd1-11b2-0a00-9608275dc400
uuid:bf378643-1dd1-11b2-0a00-810000000000
endstream
endobj
57 0 obj
<>
endobj
58 0 obj
<>
endobj
72 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Thumb 41 0 R/Type/Page>>
endobj
1 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Thumb 43 0 R/Type/Page>>
endobj
4 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Thumb 45 0 R/Type/Page>>
endobj
17 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Thumb 47 0 R/Type/Page>>
endobj
30 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/Thumb 49 0 R/Type/Page>>
endobj
38 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Thumb 51 0 R/Type/Page>>
endobj
166 0 obj
[170 0 R]
endobj
167 0 obj
<>stream
q
0 0 612 792 re
W n
BT
0.85091 0.85091 0.85091 rg
/T1_0 19 Tf
0.6303 0.7762 -0.7762 0.6303 16.7778 46.0632 Tm
(Personal non-commercial use only. The Journal of Rheumatology. Copyright\
\251 2004. All rights reserved)Tj
ET
Q
1 g
/GS0 gs
0 792 m
0 792 l
f
q
-1 793 614 -794 re
W n
q
0 792.03 612 -792 re
W n
BT
0 0 0 1 k
/GS1 gs
/T1_1 1 Tf
-0.01511 Tc 0.02499 Tw 10 0 0 10 54 713.1616 Tm
[(OPTIMAL)-187.4 (W)110.7 (A)91.8 (YS )17.7 (T)17.7 (O COMBINE LEFLUNOMIDE)]TJ
0 -1.2 TD
[(WITH )54.8 (ANOTHER DMARD OR BIOLOGICAL)-150.3 (AGENT)]TJ
-0.00011 Tc T*
[(Dosing r)17.7 (egimens)]TJ
/T1_2 1 Tf
0.1851 Tw T*
(In their questionnaire responses, only 33% of the Expert)Tj
0.13989 Tw T*
(Panel indicated they use a loading dose when prescribing)Tj
0.15359 Tw T*
(leflunomide with another DMARD; 24% and 43% of the)Tj
0.2874 Tw T*
[(Panel, respectively)64.8 (, reported they rarely or never use a)]TJ
0.0175 Tw T*
[(loading dose, usually because of concern about side ef)17.7 (fects.)]TJ
0.026 Tw T*
(Of those who do use a loading dose, 62% use 100 mg daily)Tj
0.17751 Tw T*
(for 3 days, 23% 100 mg daily for 2 days; 16% reported)Tj
-0.02271 Tw T*
(using doses of 40\32060 mg daily for 4\3206 days or 100 mg twice)Tj
0.14101 Tw T*
[(weekly for 3 doses, with 20 mg on other days. )17.7 (The most)]TJ
0.1055 Tw T*
(frequent maintenance dose, reported by 79% of the Panel,)Tj
0.0327 Tw T*
[(was 20 mg daily)64.8 (. Of those changing the initial maintenance)]TJ
0.0762 Tw T*
(dose, 28% would start with 10 mg, increasing it to 20 mg,)Tj
0.0526 Tw T*
[(and 72% would do the reverse. )17.6 (Three-quarters of the Panel)]TJ
0.07111 Tw T*
(reduced the maintenance dose because of an adverse event)Tj
0.2354 Tw T*
(listed in the product insert, 13% because of an unlisted)Tj
-0.0061 Tw T*
[(adverse event, and 13% at the patient\325)54.8 (s request. )17.7 (The mainte-)]TJ
0.0976 Tw T*
[(nance dose was increased by 44% because of lack of ef)17.7 (fi-)]TJ
0.0036 Tw T*
(cacy and by 48% because of a partial, or less than expected,)Tj
0.1828 Tw T*
[(response. For combination therapy)64.8 (, however)39.7 (, none of the)]TJ
0.3148 Tw T*
(Panel experts increases the leflunomide dose above 20)Tj
0.0542 Tw T*
[(mg/day)64.8 (. In patients not responding to this dose, the experts)]TJ
0.02499 Tw T*
(would add MTX 7.5\32010 mg per week.)Tj
/T1_1 1 Tf
0 -2.4 TD
[(Choosing the appr)17.7 (opriate combination tr)17.7 (eatment)]TJ
/T1_2 1 Tf
-0.02029 Tw 0 -1.22 TD
(Following the workshop discussions it was suggested that in)Tj
-0.0224 Tw T*
(MTX partial responders, leflunomide might be added before)Tj
0.0565 Tw T*
(using a biological agent. In patients with a partial response)Tj
0.00259 Tc 0.3723 Tw T*
(to MTX plus leflunomide, treatment with leflunomide)Tj
-0.00011 Tc 0.02541 Tw T*
(should be stopped and a biological agent substituted. It was)Tj
0.0412 Tw T*
[(agreed, however)39.7 (, that more data are needed on leflunomide)]TJ
0.052 Tw T*
(+ biological agent combinations, and that currently there is)Tj
0.0287 Tw T*
(more experience to support the use of MTX in such combi-)Tj
0.1084 Tw T*
[(nations. )54.8 (Although in principle any biological agent can be)]TJ
0.06461 Tw T*
(combined with leflunomide, experience is minimal and the)Tj
-0.022 Tw T*
(Panel recommended caution when using such combinations.)Tj
/T1_1 1 Tf
0.02499 Tw 0 -2.4 TD
(Patient monitoring)Tj
/T1_2 1 Tf
0.2581 Tw 0 -1.2 TD
(All the experts reported in their questionnaire that they)Tj
-0.00771 Tw T*
(always carefully monitor patients receiving combinations of)Tj
-0.02789 Tw T*
[(leflunomide and another DMARD. )17.8 (The Panel recommended)]TJ
0.0764 Tw T*
(that all patients receiving leflunomide in combination with)Tj
-0.01849 Tw T*
(MTX should have regular blood pressure measurements and)Tj
0.052 Tw T*
(laboratory tests. Detailed recommendations, particularly on)Tj
0.32449 Tw T*
[(the intervals for)39.7 (, and interpretation of, LFT)73.8 (, are under)]TJ
0.02499 Tw T*
(further discussion.)Tj
/T1_1 1 Tf
0 Tw 0 -2.4 TD
(CONCLUSION)Tj
/T1_2 1 Tf
-0.0051 Tc 0.1219 Tw 0 -1.2 TD
[(Leflunomide is ef)17.6 (fective and well tolerated when added to)]TJ
0.0235 Tw T*
(either MTX treatment or another DMARD. Experience with)Tj
0.0618 Tw T*
(leflunomide plus infliximab is limited, but the Expert Panel)Tj
0.23711 Tw 26.4 62.62 Td
(believe the results are encouraging. Combination therapy)Tj
0.14709 Tw T*
(with leflunomide therefore has a place in the treatment of)Tj
0.10851 Tw T*
[(RA. Caution is advised, however)39.6 (, when using combination)]TJ
-0.0027 Tw T*
[(treatment: the patient\325)54.8 (s safety should be carefully monitored.)]TJ
/T1_1 1 Tf
-0.00011 Tc 0 Tw 0 -2.4 TD
(REFERENCES)Tj
/T1_2 1 Tf
0.02499 Tw 8 0 0 8 325 643.4616 Tm
[(1.)-875.1 (Kremer J. Methotrexate and leflunomide: biochemical basis for)]TJ
1.675 -1.2125 Td
(combination therapy in the treatment of rheumatoid arthritis. Semin)Tj
0 -1.2125 TD
(Arthritis Rheum 1999;29:14-26.)Tj
-1.675 -1.2125 Td
[(2.)-875.1 (Fox RI, Herrmann ML, Frangou CG, et al. Mechanism of action for)]TJ
1.675 -1.2125 Td
(leflunomide in rheumatoid arthritis. Clin Immunol )Tj
0 Tc 0 Tw T*
(1999;93:198-208.)Tj
-0.00011 Tc 0.02499 Tw -1.675 -1.2125 Td
[(3.)-875.1 (Dimitrova P)110.7 (,)-0.1 ( Skapendo )54.8 (A, Herrmann M, Schleyerbach R, Kalden J,)]TJ
1.675 -1.2125 Td
(Schulze-Koops H. Restriction of de novo pyrimide biosynthesis)Tj
T*
[(inhibits )17.7 (Th1 cell activation and promotes )17.7 (Th2 cell dif)17.7 (ferentiation. )]TJ
T*
(J Immunol 2002;169:3392-9.)Tj
-1.675 -1.2125 Td
[(4.)-875.1 (Feldmann M, Maini RN. )54.8 (Anti-TNF alpha therapy of rheumatoid)]TJ
1.675 -1.2125 Td
[(arthritis: what have we learned? )54.8 (Ann Rev Immunol )]TJ
0 Tc 0 Tw T*
(2001;19:163-96.)Tj
-0.00011 Tc 0.02499 Tw -1.675 -1.2125 Td
[(5.)-875.1 (W)79.9 (einblatt M, Kremer J, Coblyn J, Maier )54.8 (A, Helfgott S, Morrell M.)]TJ
1.675 -1.2125 Td
[(Pharmacokinetics, safety)64.8 (, and ef)17.7 (ficacy of combination treatment)]TJ
T*
(with methotrexate and leflunomide in patients with active )Tj
T*
[(rheumatoid arthritis. )54.8 (Arthritis Rheum 1999;42:1322-8.)]TJ
-1.675 -1.2125 Td
[(6.)-875.1 (Kremer J, Genovese M, Cannon G, Caldwell J, Cush J, Furst D.)]TJ
1.675 -1.2125 Td
(Concomitant leflunomide therapy in patients with active )Tj
T*
[(rheumatoid arthritis despite stable doses of methotrexate. )54.8 (A)]TJ
T*
[(randomized, double-blind, placebo-controlled trial. )54.8 (Ann Intern Med)]TJ
0 Tc 0 Tw T*
(2002;137:726-33.)Tj
-0.00011 Tc 0.02499 Tw -1.675 -1.2125 Td
[(7.)-875.1 (Kremer J, Genvose M, Cannon G, Caldwell J, Cush J, )17.7 (W)79.9 (eisman M.)]TJ
1.675 -1.2125 Td
(Combination of leflunomide and methotrexate in patients with)Tj
T*
(active rheumatoid arthritis failing MTX monotherapy: an open)Tj
T*
[(label extension study [abstract]. )54.8 (Arthritis Rheum 2001;46)]TJ
0 Tw T*
(Suppl:S144.)Tj
0.02499 Tw -1.675 -1.2125 Td
[(8.)-875.1 (Cohen S, Schif)17.7 (f M, )17.7 (W)79.9 (eaver )54.8 (A, )17.7 (T)69.9 (esser J, Baraf H, Maestrello S.)]TJ
1.675 -1.2125 Td
(Leflunomide \(LEF\) as initial therapy with methotrexate \(MTX\))Tj
T*
(added for rheumatoid arthritis patients with active disease)Tj
T*
[([abstract]. )54.8 (Arthritis Rheum 2002;46 Suppl:S352.)]TJ
-1.675 -1.2125 Td
[(9.)-875.1 (Dougados M, Combe B, van Riel P)110.7 (, Masek B, Brin S, Emery P)110.7 (.)]TJ
1.675 -1.2125 Td
[(Ef)17.7 (ficacy and safety of leflunomide \(LEF\) in combination with)]TJ
T*
(sulfasalazine \(SSZ\) versus sulfasalazine in patients with rheumatoid)Tj
T*
[(arthritis: results from the RELIEF study [abstract]. )54.8 (Annual)]TJ
T*
[(European Congress of Rheumatology)64.8 (, Stockholm, Sweden, June)]TJ
T*
[(12-15, 2002. [Internet]. )54.8 (Accessed February 13, 2004. )54.8 (A)74 (vailable)]TJ
T*
[(from: http://www)64.8 (.eular)54.8 (.or)17.7 (g/eular2002.cfm)]TJ
-2.175 -1.2125 Td
[(10.)-875.1 (Kiely P)110.7 (, Johnson D. Infliximab and leflunomide combination)]TJ
2.175 -1.2125 Td
[(therapy in rheumatoid arthritis: an open-label study)64.8 (. Rheumatology)]TJ
0 Tc 0 Tw T*
(2002;41:631-7.)Tj
-0.00011 Tc 0.02499 Tw -2.1381 -1.2125 Td
[(1)36.8 (1)-0.1 (.)-875.1 (Struppler C, )17.7 (Thies )17.7 (W)91.9 (, Schattenkirchner M, Kellner H. Safety and)]TJ
2.1381 -1.2125 Td
[(ef)17.7 (ficacy of leflunomide and infliximab in rheumatoid arthritis \(RA\))]TJ
0 Tc T*
[(patients [abstract]. )54.8 (Ann Rheum Dis 2002;61 Suppl:S388.)]TJ
-0.00011 Tc -2.175 -1.2125 Td
[(12.)-875.1 (Schif)17.7 (f M, Cush J, Singhal )54.8 (A, et al. )17.7 (The safety and ef)17.7 (ficacy of)]TJ
2.175 -1.2125 Td
(leflunomide in combination with infliximab in patients with)Tj
T*
[(rheumatoid arthritis [abstract]. )54.8 (Annual European Congress of)]TJ
T*
[(Rheumatology)64.9 (, Stockholm, Sweden, June 12-15, 2002. [Internet].)]TJ
T*
[(Accessed February 13, 2004. )54.8 (A)74 (vailable from:)]TJ
0 Tw T*
[(http://www)64.8 (.eular)54.8 (.or)17.7 (g/eular2002.cfm)]TJ
0.02499 Tw -2.175 -1.2125 Td
[(13.)-875.1 (Patel S, Ber)17.7 (gen )17.7 (W)91.9 (, Kraemer )54.8 (A, Keenan G. Ef)17.7 (ficacy and safety of)]TJ
2.175 -1.2125 Td
[(Remicade \(infliximab\) and )54.8 (Arava \(leflunomide\) in rheumatoid)]TJ
T*
[(arthritis [abstract]. )54.8 (Arthritis Rheum 2001;44 Suppl:S189.)]TJ
-2.175 -1.2125 Td
[(14.)-875.1 (Hansen K, Cush J, Singhal )54.8 (A, Cooley D, Patel S, Genovese M. )17.7 (The)]TJ
2.175 -1.2125 Td
[(safety and ef)17.7 (ficacy of leflunomide \(LEF\) in combination with)]TJ
T*
[(infliximab \(INF\) in rheumatoid arthritis [abstract]. )54.8 (Arthritis Rheum)]TJ
0 Tc T*
(2001;44 Suppl:S84.)Tj
ET
0 0 0 1 K
54 54 m
558 54 l
S
BT
/T1_3 1 Tf
-0.00011 Tc 8 0 0 8 354.2144 35.9844 Tm
[(The Journal of Rheumatology 2004, V)110.7 (olume 31, Supplement 71)]TJ
0 Tc 0 Tw -37.5268 -0.0313 Td
(30)Tj
ET
0 0 0 0 k
/GS0 gs
109.25 59.09 396.47 -10.83 re
f*
0.5 w
109.25 59.09 396.47 -10.83 re
S
Q
Q
q
0 0 612 792 re
W n
BT
0 0 0 rg
/GS2 gs
/T1_4 8 Tf
119.868 51 Td
(Personal, non-commercial use only. The Journal of Rheumatology. Copyri\
ght \251 2004. All rights reserved.)Tj
ET
Q
BT
0 g
/GS2 gs
/T1_5 1 Tf
10 0 0 10 540 17 Tm
( )Tj
0 0.48627 0.77255 rg
/GS2 gs
-7.22298 0 Td
(www.jrheum.org)Tj
0 g
/GS2 gs
-16.72996 0 Td
(Downloaded on March 29, 2024 from )Tj
ET
endstream
endobj
51 0 obj
<>stream
8;Z\7$ZrK&!tQ@2:Rl>l6c&>in!%pfB`sI(eHd]ti3!CYE#Z
oG0,3GaRNE#Vkhr;RWD0\K9^S@,!k6p)G/_P2^5]3A;Os=!<'d?;KZ?k#gqlV."QC
Lj+)jXM]`0/p*ek2;2Ik8BTke#Y'NH,_"P"$105fmc5iD5U]_X]M=_;)k#QVAeQ0#
*u7'iWis4Ys#R%1W3D"dM0T)6]uYLj=F1,Y)??1
R?(1Bj;qCkE_$"dq?Z8?^tf8tGCSlF3nJJj*C+oulnIRsFsK1CS[QdR-("JLB1ui[
!+@3Ca?!M>V8opGoru,g"'8d#L"YpGF0e#?oWm^?Qpn*k\+uq[@JdPPrm5ai<\/
F,[GTq[-a*<=`dEf5`IgF-Q;V?oBE6oD04T305#D6nE@9Tq.Y.5[*?L?\_+Ao[W%T
p;/F,i907`@$h_^+R4V9'XcTdmM,[JR]$N@#EN`jqDG0I;I%BacZ"9,Na/t`.6!Ff
+`dp,EH\eB#JqFPp_a&t/Z8O~>
endstream
endobj
55 0 obj
[/Indexed/DeviceRGB 255 54 0 R]
endobj
54 0 obj
<>stream
J,g]g+e/h_!_gCtO=0f)$P%cIi8Zdfc5&3j_8$7g.@L`YKUJNGBP\poR=_;Dl'P(T
(7Boo^^S:71(MN]ZQX/+Cbu.lK"p74pe1T%s.DY%&\1TdJhr54.M9au6>79n6`Q:4
PbLSZTLEE(8E@'*1mg_*eTnN*;*'V3+gm-EEetX%;Bo$ur2ss*N`.-!.kG_q6GDD'
dKoL!8Ka#EV,@V!\j8ZFbp6EE<9cn=N6j0nf;(&;QU6bUD')c@\
9-d\DA=cZ0Q>gIM$$;cd2O@&a;X,Nn_aP(]I1aRc(K1^ue>
gF/(+GaKo$qneLWDrQ#;5\S(\$q'4Q,85`-8;S(=Z"WSBOV*FM)4,?B],R
endstream
endobj
131 0 obj
<>
endobj
81 0 obj
<>
endobj
79 0 obj
<>
endobj
75 0 obj
<>
endobj
118 0 obj
<>
endobj
149 0 obj
<>
endobj
74 0 obj
<>
endobj
109 0 obj
<>stream
HU{PSgrE1KrUV:DR^$<"/ <
Yl}tu[g2S۞~Fv윙|sw~s~g}܌aN]׆Sy{ű)o;17Yf6ce
2gVh;JUֆZYpŦUc"0m;ss.ADOHkuop[Bx!HK{ӎ
aAӾ))^-x,S4_Dbal5VLс4XΣ}бiBoeƉX!'O;o%Če5k9k״."XYA$#mfb|[{{ҙTY.TZiѢE/~I+*1(燥ǖ~ce&vZ&{>rڨef]qtplq)y 1̱o_w-uص3[ϩGSe5rI~Q^zV\#NdIJs +:ACЅy %gvtz 3S)4
XCrcFW*2%z#䐁V4<ӑ5¿^=dυ`>
͞`ɦ&iwj܇l2"c2eL6ruv=#9e:G6g(U3:#,**)2X]"zAA%rE\tYde
S9;SRv4B%vAG
[kȔ1[Q'_̪RMuOGݦ[Wm!ЃH>sc%c0@Gut,NƋ?,(*nNE9遼me<[QH,ۯR+7ﯙ:M㌇q;]LH%%<3T?AC'^& 6L B)Ɇ[FkSLę8jؿCyshZ$ڳKlg"yQIZMnMn[ EvCZ^2#d937c{;*:P;Ǒ6jF/ MY<"d݁,%h1 SԩsP/%BP\^ܓ(pݚE)->$GcFe\Lr
}PlREp[mGcJ~'aS3|>>l8(
ݫ_}5k+Oܾ}0)銿Oni92x5q)fvJd<wNNV8'/%G\DuC.aW郘Æ݃ 㱭ID9㌭xn\ W`֫/eOG_^}b_*2Xv?DQYp#HrKս/~