Oafp 06 2009 Ra
-
Upload
lawrencejacobs -
Category
Health & Medicine
-
view
416 -
download
0
description
Transcript of Oafp 06 2009 Ra
Challenges & OpportunitiesChallenges & Opportunitiesin the Treatment of RAin the Treatment of RA
Lawrence A Jacobs, MDLawrence A Jacobs, MDJune 19, 2009June 19, 2009
Rheumatology AssociatesRheumatology AssociatesTulsa, OklahomaTulsa, Oklahoma
Why Early Diagnosis & Treatment?Why Early Diagnosis & Treatment?
Clinical Spectrum of RAClinical Spectrum of RAClinical Spectrum of RAClinical Spectrum of RA
Images courtesy of J. Cush, 2002.Images courtesy of J. Cush, 2002.
Joint Erosions Occur Early in RAJoint Erosions Occur Early in RA
00
1010
2020
3030
00 11 22 33
Up to 93% of patients with 2 years of RA may have radiographic abnormalities
Rate of progression is significantly more rapid in the first year than in the second and third years
Radiographic changes in the feet are important indicators of disease progression in RA
Up to 93% of patients with 2 years of RA may have radiographic abnormalities
Rate of progression is significantly more rapid in the first year than in the second and third years
Radiographic changes in the feet are important indicators of disease progression in RA
MTP
Total
Hand
MTP
Total
Hand
van der Heijde DM et al. J Rheumatol. 1995;22:1792–1796;Fuchs HA et al. J Rheumatol. 1989;16:585–591; McQueen FM, et al. Ann Rheum Dis. 1998;57:350–356.
van der Heijde DM et al. J Rheumatol. 1995;22:1792–1796;Fuchs HA et al. J Rheumatol. 1989;16:585–591; McQueen FM, et al. Ann Rheum Dis. 1998;57:350–356.
YearYear
% o
f J
oin
ts A
ffec
ted
%
of
Jo
ints
Aff
ecte
d
Four of Seven Criteria RequiredFour of Seven Criteria Required
Morning Stiffness lasting 1 Hour or moreMorning Stiffness lasting 1 Hour or more Sort tissue swelling (Synovitis) of 3 or Sort tissue swelling (Synovitis) of 3 or
more joints X 6 weeksmore joints X 6 weeks Swelling of PIP, MCP or Wrist Joints X 6 Swelling of PIP, MCP or Wrist Joints X 6
weeksweeks Symmetrical arthritis X 6 WeeksSymmetrical arthritis X 6 Weeks Subcutaneous Nodules (Vasculitis)Subcutaneous Nodules (Vasculitis) Positive Rheumatoid Factor or CCPPositive Rheumatoid Factor or CCP Radiographic Erosions or periarticular Radiographic Erosions or periarticular
osteopeniaosteopenia
Biologic DMARDs Biologic DMARDs
Efficacy: Signs and Symptoms of DiseaseEfficacy: Signs and Symptoms of Disease
Etanercept + MTX: ACR Response Rates at 24 Weeks
Etanercept + MTX: ACR Response Rates at 24 Weeks
*P 0.001; †P 0.05Weinblatt ME, et al. N Engl J Med. 1999;340:253–259.*P 0.001; †P 0.05Weinblatt ME, et al. N Engl J Med. 1999;340:253–259.
00
1010
2020
3030
4040
5050
6060
7070
8080
ACR-20ACR-20 ACR-50ACR-50 ACR-70ACR-70
% o
f P
atie
nts
% o
f P
atie
nts
*71*
71
2727
*39*
39
33
†15†
15
00
Etanercept 25 mg + MTX
Placebo + MTX
Etanercept 25 mg + MTX
Placebo + MTX
Adalimumab + MTX (ARMADA):ACR Response Rates at 24 and 52 Weeks
Adalimumab + MTX (ARMADA):ACR Response Rates at 24 and 52 Weeks
*P ≤ 0.001ARMADA = Anti-TNF Research Program of the Monoclonal Antibody D2E7 [adalimumab] in Rheumatoid Arthritis StudyWeinblatt ME, et al. Arthritis Rheum. 2003;48:35–45; Data on file; Abbott Laboratories.
*P ≤ 0.001ARMADA = Anti-TNF Research Program of the Monoclonal Antibody D2E7 [adalimumab] in Rheumatoid Arthritis StudyWeinblatt ME, et al. Arthritis Rheum. 2003;48:35–45; Data on file; Abbott Laboratories.
Placebo + MTX
Adalimumab 40 mg EOW + MTX
Placebo + MTX
Adalimumab 40 mg EOW + MTX
1515 88
55
*66*
66
*54*
54
*27*
27
00
1010
2020
3030
4040
5050
6060
7070
ACR-20
ACR-20
ACR-50ACR-50 ACR-70
ACR-70
% o
f P
atie
nts
% o
f P
atie
nts
7070
4949
2525
24 Weeks (Double Blind)
24 Weeks (Double Blind)
52 Weeks (Open Label Extension)
52 Weeks (Open Label Extension)
ACR-20
ACR-20
ACR-50ACR-50 ACR-70
ACR-70
Adalimumab + MTX: Sustained Efficacy Over 5 YearsAdalimumab + MTX: Sustained Efficacy Over 5 Years
Breedveld FC, et al. Arthritis Rheum. 2003;48(Suppl):S118 [Abstract 198].Breedveld FC, et al. Arthritis Rheum. 2003;48(Suppl):S118 [Abstract 198].
MonthsMonths
ACR-20
ACR-50
ACR-70
ACR-20
ACR-50
ACR-70
% o
f P
atie
nts
% o
f P
atie
nts
(n = 53) (n = 53) (n = 36)(n = 36)
68686262
7575
6363
7777
30303636
5050 50504646
88 1111
28282424 2222
00
1010
2020
3030
4040
5050
6060
7070
8080
1212 2424 3636 4848 6060
Biologic DMARDs
Efficacy: Patients With Early RA
Biologic DMARDs
Efficacy: Patients With Early RA
Etanercept in Early RA: HAQ-DI Scores at 24 Months
Etanercept in Early RA: HAQ-DI Scores at 24 Months
≥ 0.5 Improvement≥ 0.5 Improvement ≥ 1.0 Improvement≥ 1.0 Improvement%
of
Pat
ien
ts%
of
Pat
ien
ts
00
1010
2020
3030
4040
5050
6060
3737
*55*
55
25252929
Etanercept25 mg
Etanercept25 mg
MTX20 mgMTX
20 mgEtanerce
pt25 mg
Etanercept
25 mg
MTX20 mgMTX
20 mg
7070
*P 0.001Genovese MC, et al. Arthritis Rheum. 2002;46:1443–1450.*P 0.001Genovese MC, et al. Arthritis Rheum. 2002;46:1443–1450.
Safety Considerations With Biologic DMARDsSafety Considerations With Biologic DMARDs
Serious infections
Opportunistic infections (TB)
Malignancies
Demyelination
Hematologic abnormalities
Administration reactions
Congestive heart failure
Autoantibodies and lupus
Serious infections
Opportunistic infections (TB)
Malignancies
Demyelination
Hematologic abnormalities
Administration reactions
Congestive heart failure
Autoantibodies and lupus
TEMPO: Infections and Serious Infections Etanercept + Methotrexate (at 52 Weeks)
TEMPO: Infections and Serious Infections Etanercept + Methotrexate (at 52 Weeks)
Number of Number of patientspatients
MTXMTX(n = 228)(n = 228)
Etanercept Etanercept (n = 223)(n = 223)
MTX + MTX + Etanercept Etanercept (n = 231)(n = 231) PP value* value*
Any Any infectioninfection††
148148(64.9%)(64.9%)
134134(60.1%)(60.1%)
158158(68.4%)(68.4%)
0.190.19
Serious Serious infectionsinfections
1010(4.4%)(4.4%)
1010(4.5%)(4.5%)
1010(4.3%)(4.3%)
1.001.00
*Fisher exact test; †No incidence of tuberculosis was noted in any treatment group. Klareskog L. Data presented at EULAR. Lisbon, Portugal, June 2003.*Fisher exact test; †No incidence of tuberculosis was noted in any treatment group. Klareskog L. Data presented at EULAR. Lisbon, Portugal, June 2003.
Infliximab: Postmarketing Infliximab: Postmarketing Reports of TuberculosisReports of Tuberculosis
Infliximab: Postmarketing Infliximab: Postmarketing Reports of TuberculosisReports of Tuberculosis
277 cases of active TB
All cases were within 6 months of treatment United States: 86 cases
55 cases in patients with RA 18 cases in patients with Crohn’s disease 13 cases in patients with unspecified disease 0.2 cases/1000 pt-years
European Union: 191 cases 1.4 cases/1000 pt-years
277 cases of active TB
All cases were within 6 months of treatment United States: 86 cases
55 cases in patients with RA 18 cases in patients with Crohn’s disease 13 cases in patients with unspecified disease 0.2 cases/1000 pt-years
European Union: 191 cases 1.4 cases/1000 pt-years
FDA Arthritis Advisory Committee meeting. March 4, 2003.FDA Arthritis Advisory Committee meeting. March 4, 2003.
August 2002August 2002August 2002August 2002
Etanercept: Malignancies and LymphomasEtanercept: Malignancies and Lymphomas
RA Clinical Trials
Patients 1272
Patient-years of follow-up 3806
Expected malignancies* 35
Observed malignancies 35
Malignancy SIR 1.0
Observed lymphomas 9
Lymphoma SIR 3.5
RA Clinical Trials
Patients 1272
Patient-years of follow-up 3806
Expected malignancies* 35
Observed malignancies 35
Malignancy SIR 1.0
Observed lymphomas 9
Lymphoma SIR 3.5*NCI (SEER), 2001, adjusted for age, gender distribution; SIR = standardized incidence ratioMoreland LW. Arthritis Rheum. 2002;46(suppl):S533. Abstract 427. Briefing document, FDA Arthritis Advisory Committee meeting. March 4, 2003.
*NCI (SEER), 2001, adjusted for age, gender distribution; SIR = standardized incidence ratioMoreland LW. Arthritis Rheum. 2002;46(suppl):S533. Abstract 427. Briefing document, FDA Arthritis Advisory Committee meeting. March 4, 2003.
Patients Patients With Disease With RACrohn’s
Patients 12981106
Patient-years of follow-up 24581646
Expected non-lymphoma malignancies* 17 10
Malignancy SIR 0.92.1
Observed lymphomas 4 2
Lymphoma SIR 6.48.7
Patients Patients With Disease With RACrohn’s
Patients 12981106
Patient-years of follow-up 24581646
Expected non-lymphoma malignancies* 17 10
Malignancy SIR 0.92.1
Observed lymphomas 4 2
Lymphoma SIR 6.48.7
Infliximab: Malignancies and LymphomasInfliximab: Malignancies and Lymphomas
*NCI (SEER), 2000, adjusted for age, sex distribution; SIR = standardized incidence ratioBriefing document, FDA Arthritis Advisory Committee meeting. March 4,2003.*NCI (SEER), 2000, adjusted for age, sex distribution; SIR = standardized incidence ratioBriefing document, FDA Arthritis Advisory Committee meeting. March 4,2003.