%PDF-1.4
%
46 0 obj
<>
endobj
43 0 obj
<>
endobj
341 0 obj
<>stream
Acrobat Distiller 4.05 for Macintosh
2004-09-13T13:14:57Z
2024-03-28T17:04:19-07:00
QuarkXPressª 4.11: AdobePS 8.8.0 (301)
2024-03-28T17:04:19-07:00
application/pdf
Heather
2003-449.oct
uuid:03aaa9aa-1dd2-11b2-0a00-fa0927bd7700
uuid:03aaa9ad-1dd2-11b2-0a00-900000000000
endstream
endobj
32 0 obj
<>
endobj
33 0 obj
<>
endobj
47 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Thumb 16 0 R/Type/Page>>
endobj
1 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Thumb 18 0 R/Type/Page>>
endobj
4 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Thumb 20 0 R/Type/Page>>
endobj
7 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Thumb 22 0 R/Type/Page>>
endobj
10 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Thumb 24 0 R/Type/Page>>
endobj
13 0 obj
<>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/Thumb 26 0 R/Type/Page>>
endobj
368 0 obj
[373 0 R]
endobj
369 0 obj
<>stream
q
0 0 612 792 re
W n
BT
0.85091 0.85091 0.85091 rg
/T1_0 19 Tf
0.6234 0.7818 -0.7818 0.6234 10.4844 52.3976 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
-1 793 587 -785 re
W n
q
0 792.03 612 -792 re
W n
BT
0 0 0 1 k
/GS1 gs
/T1_1 1 Tf
-0.00011 Tc 0.1705 Tw 10 0 0 10 43 740.1616 Tm
(lifetime history of the disease under study along with its)Tj
-0.0002 Tc 0 Tw 0 -1.19 TD
(treatment)Tj
0 Tc 6.5 0 0 6.5 80.7563 731.5616 Tm
(26\32029)Tj
-0.00011 Tc 0.1729 Tw 10 0 0 10 97.0062 728.2616 Tm
(. Furthermore, the quality of the data in the)Tj
0.2926 Tw -5.4006 -1.19 Td
(claims database is dependent on the willingness of the)Tj
0.2513 Tw T*
(physician to fill out \(electronically or otherwise\) claims)Tj
0.2926 Tw T*
(forms with the level of detail needed in epidemiologic)Tj
0.26781 Tw T*
(research. For example, the presence of elevated hepatic)Tj
0.1163 Tw T*
(enzymes may not be universally and consistently reported)Tj
0.0587 Tw T*
[(by the clinicians in the claims database, resulting in under)20 (-)]TJ
0.1996 Tw T*
[(reporting of these )55 (AE. Inconsistencies in reporting could)]TJ
0.1992 Tw T*
(produce reporting bias, particularly if the severity of the)Tj
0.29671 Tw T*
(hepatic enzyme abnormalities and/or concurrent therapy)Tj
0.0164 Tw T*
(such as MTX or LEF treatment influenced the likelihood of)Tj
0.1954 Tw T*
(reporting a claims event. In addition, information on the)Tj
-0.01421 Tw T*
[(severity of RA)-181 (was not available, nor were data on RA)-181 (treat-)]TJ
0.02499 Tw T*
(ments prior to the observation period known.)Tj
-0.0341 Tw 1.2 -1.17 Td
(In conclusion, the incidence rate of the \322all-AE\323 endpoint)Tj
0.16071 Tw -1.2 -1.17 Td
[(was significantly lower for patients with RA)-356 (treated with)]TJ
0.2606 Tw 0 -1.17 TD
(LEF monotherapy compared to subjects receiving MTX)Tj
0.0199 Tc 0.54961 Tw T*
[(monotherapy)65 (, other DMARD monotherapy)65 (, and no)]TJ
-0.00011 Tc 0.19431 Tw T*
[(DMARD. )18 (The incidence of the \322all-AE\323 endpoint in the)]TJ
-0.02769 Tw T*
(LEF + MTX group was also lower compared to other 2-drug)Tj
-0.0284 Tw T*
(therapy combinations, including DMARD + MTX, although)Tj
0.0495 Tw T*
(this was not statistically significant. For hepatic events, the)Tj
0.0209 Tw T*
(calculated incidence rates were comparable for leflunomide)Tj
0.0013 Tw T*
(and the other monotherapy comparators. Overall, the risk of)Tj
0.2285 Tw T*
(the evaluated adverse events observed with leflunomide,)Tj
-0.01151 Tw T*
(alone and in combination with MTX, was comparable to the)Tj
-0.00281 Tw T*
(risk with other disease modifying antirheumatic agents used)Tj
0.02499 Tw T*
(in the treatment of RA.)Tj
/T1_2 1 Tf
0 Tw 0 -2.4 TD
(REFERENCES)Tj
/T1_1 1 Tf
0.02499 Tw 8 0 0 8 50 376.0618 Tm
[(1.)-875 (Myers R, Hyslop )18 (T)74 (, Gerrity M, et al. Physician intention to )]TJ
1.675 -1.2125 Td
(recommend complete diagnostic evaluation in colorectal cancer)Tj
0 -1.2125 TD
(screening. Cancer Epidemiol Biomarkers Prev 1999;8:587\32093.)Tj
-1.675 -1.2125 Td
[(2.)-875 (Leone F)80 (, Grana J, McDermott P)111 (, MacPherson S, Hanchak N, Fish )]TJ
1.675 -1.2125 Td
(J. Pharmaceutically-based severity stratification of an asthmatic )Tj
0 Tc T*
(population. Resp Med 1999;93:788\32093.)Tj
-0.00011 Tc -1.675 -1.2125 Td
[(3.)-875 (European )55 (Agency for the Evaluation of Medicinal Products. Public)]TJ
1.675 -1.2125 Td
(statement on leflunomide. London, March 2001. [Cited May 25,)Tj
T*
[(2004]. )55 (A)74 (vailable from: http://)]TJ
0 Tw T*
[(www)65 (.emea.eu.int/pdfs/human/press/pus/561)37 (101en.pdf)]TJ
0.02499 Tw -1.675 -1.2125 Td
[(4.)-875 (FDA)-220 (with PhRMA)-220 (and )55 (AASLD. Drug-Induced Hepatotoxicity)]TJ
1.675 -1.2125 Td
(White Paper: Postmarketing considerations. November 2000. [Cited)Tj
T*
[(2002, Dec 1)37 (1]. )55 (A)74 (vailable from:)]TJ
0 Tw T*
[(http//www)65 (.fda.gov/cder/livertox/postmarket.pdf)]TJ
0.02499 Tw -1.675 -1.2125 Td
[(5.)-875 (Breslow N. Cohort analysis in epidemiology)65 (. In: )55 (Atkinson )55 (A,)]TJ
1.675 -1.2125 Td
[(Feinber)18 (g S, editors. )55 (A)-220 (celebration of statistics. New )37 (Y)100 (ork: )]TJ
T*
[(Springer)20 (-V)111 (erlag; 1985.)]TJ
-1.675 -1.25 Td
[(6.)-875 (Breslow N, Day N. Statistical methods in cancer research. )18 (V)129 (ol II.)]TJ
1.675 -1.25 Td
[(The design and analysis of cohort studies. L)55 (yon: International)]TJ
0 -1.25 TD
(Agency for Research on Cancer; 1987;82:1-406.)Tj
-1.675 -1.25 Td
[(7.)-875 (Frome E. )18 (The analysis of rates using Poisson regression models.)]TJ
1.675 -1.25 Td
(Biometrics 1983;39:665\32074.)Tj
-1.675 -1.25 Td
[(8.)-875 (Holford )18 (T)74 (. )18 (The analysis of rates and survivorship using log-linear)]TJ
1.675 -1.25 Td
(models. Biometrics 1980;36:299\320305.)Tj
31.325 73.8334 Td
[(9.)-875 (Charlson M, Pompei P)111 (, )55 (Ales K, MacKenzie C. )55 (A)-220 (new method of)]TJ
1.675 -1.25 Td
(classifying prognostic comorbidity in longitudinal studies: )Tj
T*
(development and validation. J Chron Dis 1987;40:373\32083.)Tj
-2.175 -1.25 Td
[(10.)-875 (McKendry RJ, Dale P)111 (. )55 (Adverse ef)18 (fects of low dose methotrexate)]TJ
2.175 -1.25 Td
(therapy in rheumatoid arthritis. J Rheumatol 1993;20:1850\3206.)Tj
-2.1381 -1.25 Td
[(1)37 (1.)-875 (W)40 (illiams HJ, )18 (W)40 (illkens RF)80 (, Samuelson CO Jr)40 (, et al. Comparison of)]TJ
2.1381 -1.25 Td
(low-dose oral pulse methotrexate and placebo in the treatment of)Tj
T*
[(rheumatoid arthritis. )55 (A)-220 (controlled clinical trial. )55 (Arthritis Rheum)]TJ
0 Tc 0 Tw T*
(1985;28:721\32030.)Tj
-0.00011 Tc 0.02499 Tw -2.175 -1.25 Td
[(12.)-875 (McKendry RJ, Dale P)111 (. )55 (Adverse ef)18 (fects of low dose methotrexate)]TJ
2.175 -1.25 Td
(therapy in rheumatoid arthritis. J Rheumatol 1993;20:1850-6.)Tj
-2.175 -1.25 Td
[(13.)-875 (Alarcon GS, )18 (T)35 (racy IC, Blackburn )18 (WD. Methotrexate in rheumatoid)]TJ
2.175 -1.25 Td
[(arthritis. )18 (T)70 (oxic ef)18 (fects as the major factor in limiting long-term)]TJ
T*
[(treatment. )55 (Arthritis Rheum 1989;32:671-6.)]TJ
-2.175 -1.25 Td
[(14.)-875 (Kremer JM, )55 (Alarcon GS, Lightfoot R)55 (W)-257 (Jr)40 (, et al. Methotrexate for)]TJ
2.175 -1.25 Td
(rheumatoid arthritis. Suggested guidelines for monitoring liver )Tj
T*
[(toxicity)65 (. )55 (Arthritis Rheum 1994;37:316-28.)]TJ
-2.175 -1.25 Td
[(15.)-875 (Kremer JM, Furst DE, )18 (W)80 (einblatt ME, Blotner SD. Significant)]TJ
2.175 -1.25 Td
[(changes in serum )55 (AST)-257 (across hepatic histological biopsy grades:)]TJ
T*
(prospective analysis of 3 cohorts receiving methotrexate therapy for)Tj
T*
(rheumatoid arthritis. J Rheumatol 1996;23:459-61.)Tj
-2.175 -1.25 Td
[(16.)-875 (Grove ML, Hassell )55 (AB, Hay EM, Shadforth MF)80 (. )55 (Adverse reactions)]TJ
2.175 -1.25 Td
(to disease-modifying anti-rheumatic drugs in clinical practice. )Tj
0 Tc T*
(Q J Med 2001;94:309\32019.)Tj
-0.00011 Tc -2.175 -1.25 Td
[(17.)-875 (Galindo-Rodriguez G, )55 (A)74 (vina-Zubieta JA, Russell )55 (AS, )]TJ
2.175 -1.25 Td
(Suarez-Almazor ME. Disappointing longterm results with disease)Tj
T*
[(modifying antirheumatic drugs. )55 (A)-220 (practice based study)65 (. )]TJ
0 Tc T*
(J Rheumatol 1999;26:2337\32043.)Tj
-0.00011 Tc -2.175 -1.25 Td
[(18.)-875 (Singh G, Fries JF)80 (, )18 (W)40 (illiams CA, Zatarain E, Spitz P)111 (, Bloch DA.)]TJ
2.175 -1.25 Td
[(T)70 (oxicity profiles of disease modifying antirheumatic drugs in)]TJ
T*
(rheumatoid arthritis. J Rheumatol 1991;18:188\32094.)Tj
-2.175 -1.25 Td
[(19.)-875 (W)80 (olfe F)80 (. )18 (The natural history of rheumatoid arthritis. J Rheumatol)]TJ
0 Tc 2.175 -1.25 Td
(1996;23 Suppl 44:13\32022.)Tj
-0.00011 Tc -2.175 -1.25 Td
[(20.)-875 (Pincus )18 (T)74 (, Callahan L. )18 (What is the natural history of rheumatoid)]TJ
2.175 -1.25 Td
[(arthritis? Rheum Dis Clin North )55 (Am 1993;19:123\32051.)]TJ
-2.175 -1.25 Td
[(21.)-875 (Movitt E, Davis )55 (A. Liver biopsy in rheumatoid arthritis. )55 (Am J Med)]TJ
0 Tc 0 Tw 2.175 -1.25 Td
(1953;226:516\32020.)Tj
-0.00011 Tc 0.02499 Tw -2.175 -1.25 Td
[(22.)-875 (Lefkovits )55 (A, Farrow I. )18 (The liver in rheumatoid arthritis. )55 (Ann)]TJ
0 Tc 2.175 -1.25 Td
(Rheum Dis 1955;14:162\3209.)Tj
-0.00011 Tc -2.175 -1.25 Td
[(23.)-875 (Ruderman E, Crawford J, Maier )55 (A, Liu J, Gravallese E, )18 (W)80 (einblatt)]TJ
2.175 -1.25 Td
(M. Histologic liver abnormalities in an autopsy series of patients)Tj
T*
(with rheumatoid arthritis. Br J Rheumatol 1997;36:210\3203.)Tj
-2.175 -1.25 Td
[(24.)-875 (Mills P)111 (, MacSween R, Dick )18 (W)92 (, More I, )18 (W)80 (atkinson G. Liver disease)]TJ
2.175 -1.25 Td
(in rheumatoid arthritis. Scott Med J 1980;25:18\32022.)Tj
-2.175 -1.25 Td
[(25.)-875 (Mills P)111 (, Sturrock R. Clinical associations between arthritis and liver)]TJ
0 Tc 2.175 -1.25 Td
[(disease. )55 (Ann Rheum Dis 1982;41:295-307.)]TJ
-0.00011 Tc -2.175 -1.25 Td
[(26.)-875 (Armstrong EP)111 (, Manuchehri F)80 (. )55 (Ambulatory care databases for)]TJ
2.175 -1.25 Td
[(managed care or)18 (ganizations. )55 (Am J Health Syst Pharm)]TJ
0 Tc 0 Tw T*
(1997;54:1973\32083.)Tj
-0.00011 Tc 0.02499 Tw -2.175 -1.25 Td
[(27.)-875 (Deyo RA, )18 (T)70 (aylor )18 (VM, Diehr P)111 (, et al. )55 (Analysis of automated )]TJ
2.175 -1.25 Td
(administrative and survey databases to study patterns and outcomes)Tj
T*
(of care. Spine 1994;19 Suppl 18:2083S\32091S.)Tj
-2.175 -1.25 Td
[(28.)-875 (Motheral BR, Fairman KA. )18 (The use of claims databases for)]TJ
2.175 -1.25 Td
[(outcomes research: rationale, challenges, and strategies. Clin )18 (Ther)]TJ
0 Tc 0 Tw T*
(1997;19:346\32066.)Tj
-0.00011 Tc 0.02499 Tw -2.175 -1.25 Td
[(29.)-875 (Shatin D, Drinkard C, Ster)18 (gachis )55 (A. United Health Group. In:)]TJ
2.175 -1.25 Td
[(Strom B, editor)55 (. Pharmacoepidemiology)65 (. 3rd ed. Chichester: John)]TJ
0 Tc T*
[(W)40 (iley & Sons; 2000:295\320306.)]TJ
ET
0 0 0 1 K
43 81 m
547 81 l
S
BT
/T1_3 1 Tf
-0.00011 Tc 8 0 0 8 43.5 62.9844 Tm
[(Cannon, et al: )18 (Adverse events with DMARD)]TJ
0 Tc 0 Tw 60.9375 -0.0313 Td
(1911)Tj
ET
0 0 0 0 k
/GS0 gs
96.22 85.74 396.48 -10.83 re
f*
0.5 w
96.22 85.74 396.48 -10.83 re
S
Q
Q
q
1 0 0 1 0 9 cm
0 0 612 792 re
W n
1 0 0 1 0 -9 cm
BT
0 0 0 rg
ET
/GS2 gs
BT
/T1_4 8 Tf
110.368 78 Td
(Personal, non-commercial use only. The Journal of Rheumatology. Copyri\
ght \251 2004. All rights reserved.)Tj
ET
Q
BT
0 g
/GS3 gs
/T1_5 1 Tf
10 0 0 10 540 17 Tm
( )Tj
0 0.48627 0.77255 rg
/GS3 gs
-7.22298 0 Td
(www.jrheum.org)Tj
0 g
/GS3 gs
-16.72996 0 Td
(Downloaded on March 28, 2024 from )Tj
ET
endstream
endobj
26 0 obj
<>stream
8;Z\7;0Kl##itt$j>q_Fa=n_`C9m5&G^\>JYqRsV=Ol%&eKe:$pt_Xann7RW8*ufD
*NffL%qP)%!U[\SK.?l5p*JXS*?3(br3tVHr/r;.JXa2Lq!3L].`l)m>r*n23.gcW
ek$44p/YkOA'=&NQdTNt9Afk5ZLX21-aan7>h>Qmjg-?pO)stO'i/te^&ge2_@$Cn
PfSG\Y?)k.'sZ&'6&UR^3c_(IJM0'6M6ir:=O0jmCbLi%5@j*QRc9\_SoPh4mr:.s
<'h(,=d$LS\$clrgDh)V)K])3;eq$Jf0$4A<2tSUU*W#:ALV57_=E=aD=u%oYu@\i
+'tph(Ak6V<%2j-b&LgH.M1o(5)[-h24DGqO;'QQ0tueKBVd[K"-,1OG[0$f8H?^?
A*nMuj)!5O.?s6I?F"jFXg$SCgDqo=Y'*MPlMbS5PQ]n([:@f[$hKMKF.<"b+$=62
pr4hao'L.er<98O+QDL88\]W:1QRNNO$O,mQY;$n#(s;0LIb"OZjk^CQX^X9S[LRm
_#m/qdT\4N:M1KrDn)0
&9s28l\t2957R:
0BeOAU/Yq$0eL!1ia-9`b8PM#mi"]s5EpbnNVb[;*"'\3j(ET@lF(t2*X#qe(S7SG
HhZD>6O`@o,/!X'Y/sCb`+A&+GrhN5cd7$s?Mb]=)$'V'Y3Q~>
endstream
endobj
30 0 obj
[/Indexed/DeviceRGB 255 29 0 R]
endobj
29 0 obj
<>stream
J,g]g+e/h_!_gCtO=0f)$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$qneLWDrQ#;5\S(\$q'4Q,85`-8;S(=Z"WSBOV*FM)4,?B],R
endstream
endobj
86 0 obj
<>
endobj
53 0 obj
<>
endobj
57 0 obj
<>
endobj
50 0 obj
<>
endobj
73 0 obj
<>
endobj
347 0 obj
<>
endobj
49 0 obj
<>
endobj
66 0 obj
<>stream
HUiPTW~k[M0d4ZqCADDY -4
ttC,M7-4 4@
"@@e0qBuDeL$V*jLMLnsW;U8fj85d[0~
Oz(6u~+1n8Ąq'ŦϢbLVZL+G Ռto]V``L6ya$Smr} Dgw9k5-8gX(9R2"^<ْy+d,ceRb3rG8ATHlɉM_#}8!? }c10k{Űu$aK6aXw3qdI5aI5c2Z6r
?[XXZLZgy_V֤u/X=|o+l7iYzh.-t;~8t)UNrn5.I1`:Ki$Eq:Q0;%W+SP%yJ֕-/p5@:)i.C wv[31ёE"tմD@wLG(zPst6QN'ZeԸ٦G
ɔ2ik3]5p.@bXC+^gVWi\OjŪe,yǂ]pZk]֥