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TRANSCRIPT
Improving Outcomes in
Rheumatoid Arthritis:
Comparative Effectiveness
of Current Treatments
A. Scott Mathis, PharmD
Administrative Director
Pharmacy and Medication Use
Pharmacy Department
Monmouth Medical Center
Long Branch, NJ
Faculty Presenter: A. Scott Mathis, PharmD Administrative Director, Pharmacy and Medication Use
Pharmacy Department Monmouth Medical Center
Long Branch, New Jersey Moderator:
Elena Beyzarov, PharmD Director of Scientific Affairs
Pharmacy Times Office of Continuing Professional Education Plainsboro, New Jersey
Type of Activity: Knowledge Fee: None.
Length of Webinar: 1-hour including question-and-answer session.
This activity is supported by an educational grant from Bristol -Myers Squibb.
Disclosures
A. Scott Mathis, PharmD, has no relevant financial relationships with commercial interests to disclose.
Pharmacy Times Office of Continuing Professional
and PER Planning Staff—Judy V. Lum, MPA; Elena Beyzarov, PharmD; Ann C. Lichti, CCMEP; and Donna Fausak— have no relevant financial
relationships with commercial interests to disclose.
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Learning Objectives
Describe the epidemiology and pathophysiology related to RA
Examine the clinical and economic burden of RA, as well as the goals of therapy
Discuss current management of RA focusing on recent updates to comparative effectiveness on non-biological and biological DMARDS
Explore the role of specialty pharmacy and disease therapy management programs optimizing clinical and economic patient outcomes
Improving Outcomes in
Rheumatoid Arthritis:
Comparative Effectiveness
of Current Treatments
A. Scott Mathis, PharmD
Administrative Director
Pharmacy and Medication Use
Pharmacy Department
Monmouth Medical Center
Long Branch, NJ
Epidemiology
World prevalence1 ~0.5%-1%
– China and Japan ~0.2-0.3%
– Pima and Chippewa Indians ~5.3%-6.8%
US prevalence2
– Women ~1%
– Men ~0.6%
– About 1.3 million affected
1 Helmick CG, Felson DT, Lawrence RC, et al; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58(1):15-25.
2 Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4(suppl 3):S265-S272.
Epidemiology2,3
Environmental factors
– Infectious diseases
– Smoking
– Estrogen
Genetic factors
– Twin studies
» 15-30% concordance, monozygotic
» 5% dizygotic twins
– HLA-DRB1 genotype
» Determines susceptibility and severity
2 Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4(suppl 3):S265-S272. 3 McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-2219.
Burden of Disease3
Synovial hyperplasia, cartilage damage, bony
erosion
– Erosion occurs in 80% of patients within one year
– Eroded bone does not repair
Work disability
– 1/3 in 2 years
– 50% in 10 years
Extra-articular RA
– Cardiovascular disease, 1.5-fold increase in mortality
– Lungs
– Liver
– Brain and nerves
– Rheumatoid nodules
3 McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-2219.
Costs of RA
Direct4-6
– $2000 to $10 000 per patient
– Ambulatory: medication, laboratory, primary care, specialty
care, joint injection
– Inpatient
– Extra-articular disease7
Indirect4,5
– $1500 to $22, 000 per patient
– Mortality
– Lost productivity and quality of life
4 Fautrel B, Clarke AE, Guillemin F, et al. Costs of rheumatoid arthritis: new estimates from the human capital method and comparison to the willingness-to-pay method. Med Decis Making. 2007;27(7):138-150.
5 Bansback N, Marra CA, Finckh A, Anis A. The economics of treatment in early rheumatoid arthritis. Best Prac Res Clin
Rheumatol. 2009;23(1):83-92. 6 Lanes SF, Lanza LL, Radensky PW, et al. Resource utilization and cost of care for rheumatoid arthritis and osteoarthritis i n a
managed care setting: the importance of drug and surgery costs. Arthritis Rheum. 1997;40(8):1475-1481. 7 Joyce AT, Smith P, Khandker R, Melin JM, Singh A. Hidden cost of rheumatoid arthritis (RA): estimating cost of cormorbid
cardiovascular disease and depression among patients with RA. J Rheumatol. 2009;36(4):743-752.
Pathophysiology of Joint Inflammation3
Underlying process
– Autoimmune response to environmental
and genetic factors
– Inflammation
Findings
– Joint swelling
– Synovial thickening
– Bony erosions
3 McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-2219.
Immune Cascade and
Targets3
3 McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-2219.
2010 Classification Criteria8
8 Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against
Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581.
Criteria Description Score
Sy mptoms Clinical sy nov itis/swelling in at least 1 joint not
explained by another disease
NA
Joint
inv olv ement
1 large joint
2-10 large joints
1-3 small joints (with or without large joint)
4-10 small joints (with or without large joint)
>10 joints (at least 1 small)
0
1
2
3
5
Serology Negativ e RF and negativ e ACPA
Low-positiv e RF or ACPA
High-positiv e RF or ACPA
0
2
3
Acute-phase
reactants
Normal CRP and ESR
Abnormal CRP or ESR
0
1
Duration of
sy mptoms
< 6 weeks
≥ 6 weeks
0
1
Criteria score
required
≥ 6/10
RF= rheumatoid factor
ACPA= anti-citrullinated protein/peptide
antibodies
CRP= C-reactive protein
ESR= erythrocyte sedimentation rate
Assessment of Disease Activity9
High Disease Activ ity (HDA)
• Simplif ied Disease Activ ity Index (SDAI) >26
• Disease Activ ity Score-28 (DAS28) > 5.1
• High risk of disease progression (eg, radiographic changes, joint damage)
Moderate Disease Activ ity (MDA)
• SDAI >11-26
• DAS28: 3.2-5.1
• Moderate risk of disease progression
Low Disease Activ ity (LDA)
• SDAI > 3.3-11
• DAS28: 2.6-3.1
• Low, but real risk of disease progression
Remission
• Absence of signs or sy mptoms without additional treatment
• Less than 20% of patients historically
9 Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625-639.
Assessment of Disease:
Poor Prognosis9
1 or more of the following poor prognostic
features:
– Functional limitation (per Health Assessment
Questionnaire or similar valid tools)
– Extra-articular disease (eg, presence of
rheumatoid nodules, RA vasculitis)
– Positive rheumatoid factor or ACPA
– Bony erosions by radiograph
9 Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care
Res (Hoboken). 2012;64(5):625-639.
Goals of Therapy10
Historical
– Controlled pain and joint symptoms
Current
– Controlled pain and joint symptoms
– Controlled inflammation
– Early identification and treatment
– Remission or LDA
– Prevention of joint damage and disability
– Prevention of long-term disease complications
10 Combe B. Progression in early rheumatoid arthritis. Best Prac Res Clin Rheumatol. 2009;23(1):59-69.
Supportive Care9-11
Analgesics
Non-steroidal anti-inflammatory drugs
(NSAIDs)
Alternate or complementary therapies
Exercise/occupational therapy
Corticosteroids
9 Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis
Care Res (Hoboken). 2012;64(5):625-639.
10 Combe B. Progression in early rheumatoid arthritis. Best Prac Res Clin Rheumatol. 2009;23(1):59-69. 11 Macfarlane GJ, Paudyal P, Doherty M, et al; Arthritis Research UK Working Group on Complementary
and Alternative Therapies for the Management of the Rheumatic Disease. A systematic review of evidence for the effectiveness of practitioner-based complementary and alternative therapies in the management of rheumatic
diseases: rheumatoid arthritis. Rheumatology (Oxford). 2012; 51(9):1707-1713.
Non-Biologic DMARDs9,12,13
9 Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of
disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken).
2012;64(5):625-639.
12 Isaacs JD. The changing face of rheumatoid arthritis: sustained remission for all? Nat Rev Immunol. 2010;10(8):605-611. 13 van Vollenhoven RF. Treatment of rheumatoid arthritis: state of the art in 2009. Nat Rev Rheumatol. 2009;5(10):531-541.
Medication Pharmacology Usual Dose and
Route
Adverse Effects
Auranof in* Gold salt with unknown
mechanism
3-6 mg daily oral;
3 mg giv en twice daily
Diarrhea, hy persensitiv ity reactions
Azathioprine* Antiprolif erativ e agent to
T-cells and B-cells
50-200 mg daily ; oral Hepatoxicity, my elotoxicity,
gastrointestinal toxicity
Cy closporine* T-cell activ ation inhibitor
(IL-2)
2.5-5 mg/kg per day ;
oral
Nephrotoxicity, hy pertension
Hy droxy -
chloroquine
Interf ere with antigen
processing and immune
f unction
200-400 mg daily ; oral Retinopathy
Lef lunomide (L) Anti-metabolite 10-20 mg daily ; oral Hepatotoxicity, myelotoxicity,
hy pertension
Methotrexate (M) Anti-metabolite 7.5-25 mg weekly ; oral
or subcutaneous
Hepatotoxicity, myelotoxicity,
f ibrosing alv eolitis.
Sodium
aurothiomalate*
Gold salt with unknown
mechanism
50 mg weekly ;
intramuscular
Hy persensitiv ity reactions, nephritis,
f ibrosing alv eolitis.
Sulf asalazine (S) Anti-inf lammatory and
antimicrobial
1000-1500 mg twice
daily ; oral
Hepatotoxicity, myelotoxicity,
hy persensitiv ity reactions * Not recommended in ACR 2012 due to infrequent use or lack of recent published evidence IL= interleukin
AHRQ Comparison of Non-Biologic DMARDs14
Not studied by AHRQ: auranofin, azathioprine, cyclosporine, hydroxychloroquine, sodium aurothiomalate
14 Donahue KE, Jonas D, Hansen RA, et al. Drug therapy for rheumatoid arthritis in adults: an
update. executive Summary. Comparative Effectiveness Review Number 55. AHRQ Publication No. 12-EHC025-1. Rockville, MD: Agency for Healthcare Research and Quality. April 2012. http://www.effectivehealthcare.ahrq.gov/ehc/products/203/1042/CER55_DrugTherapies-
rheumatoidarthritis_execsumm.pdf. Accessed August 14, 2012.
DMARDs Assessment vs Non-biologics Assessment vs Biologics
Lef lunomide
(L)
Disease Control (ACR20): L≈M, Data
insuf f icient to compare with S
Radiographic Response: L≈M, L≈S
Functional Capacity : L≈M, L>S
Quality of Lif e: L>M
No data av ailable
Methotrexate (M) Disease Control (ACR20): M≈L, M≈S, M≈S
Radiographic Response: M≈L, M≈S
Functional Capacity : M≈L, M≈S
Quality of Lif e: M<L
Early RA Clinical Response: M≈Ada,
M≈E
Early RA Radiologic Response:
M<TNF inhibitors
Early RA Functional Capacity :
M≈Ada
Speed of Quality of Lif e
Improv ement in Early RA: M<E
Sulf asalazine (S) Disease Control (ACR20): S≈M, S≈L
Radiographic Response: S≈M, S≈L
Functional Capacity : S<L
No data av ailable
AHRQ= Agency for Healthcare Research and Quality
ACR= American College of
Rheumatology
TNF= tumor necrosis factor
TNF Inhibitors6,12-14
6 Lanes SF, Lanza LL, Radensky PW, et al. Resource utilization and cost of care for rheumatoid arthritis and osteoarthritis in a
managed care setting: the importance of drug and surgery costs. Arthritis Rheum. 1997;40(8):1475-1481.
12 Isaacs JD. The changing face of rheumatoid arthritis: sustained remission for all? Nat Rev Immunol. 2010;10(8):605-611.
13 van Vollenhoven RF. Treatment of rheumatoid arthritis: state of the art in 2009. Nat Rev Rheumatol. 2009;5(10):531-541.
14 Donahue KE, Jonas D, Hansen RA, et al. Drug therapy for rheumatoid arthritis in adults: an update. Executive Summary. Comparative
Effectiveness Review Number 55. AHRQ Publication No. 12-EHC025-1. Rockville, MD: Agency for Healthcare Research and Quality.
April 2012. http://www.effectivehealthcare.ahrq.gov/ehc/products/203/1042/CER55_Dru gTherapies -
rheumatoidarthritis_execsumm.pdf. Accessed August 14, 2012.
Medication Pharmacology Usual Dose and Route Adverse Effects and AHRQ
Comparative Safety
Adalimumab
(Ada)
Human monoclonal TNF
blockade
40 mg ev ery 2 weeks;
subcutaneous
Injection site reactions, inf ections
Certolizumab
pegol (C)
Pegy lated Fab’ f ragment
f rom humanized monoclonal
antibody TNF blockade
200 mg ev ery two weeks or
400 mg (two 200-mg
injections) monthly ;
subcutaneous
Injection site reactions, inf ections.
Withdrawals due to lack of ef ficacy
C<Ada≈Ana≈I. Withdrawals due to
adv erse ev ents C≈I, C>E, C>R
Etanercept
(E)
Recombinant TNF receptor
(p75) dimerized on Ig f rame
TNF blockade
50 mg weekly or 25 mg
twice weekly ;
subcutaneous
Injection site reactions, inf ections.
Withdrawals due to adv erse ev ents
E<C, E<I
Golimumab
(G)
Human monoclonal TNF
blockade
50mg or 100mg ev ery 4
weeks; subcutaneous
Injection site reactions, inf ections
Inf liximab (I) Chimeric monoclonal TNF
blockade
3 mg/kg, weeks 0, 2, and 6,
then 3-10 mg/kg ev ery 4-8
weeks; intrav enous
Inf usion reactions, inf ection.
Discontinuation rates and serious
adv erse ev ents I>A. Withdrawals due
to adv erse ev ents I≈C, I>E, I>R
AHRQ Comparison of TNF Inhibitors14
14 Donahue KE, Jonas D, Hansen RA, et al. Drug therapy for rheumatoid arthritis in adults: an update. Executive Summary. Comparative Effectiveness Review Number 55. AHRQ Publication No. 12-EHC025-1. Rockville, MD: Agency for Healthcare
Research and Quality. April 2012. http://www.effecti vehealthcare.ahrq.gov/ehc/produc ts/203/1042/CER55_DrugTherapies-
rheumatoidarthritis_execsumm.pdf. Accessed August 14, 2012.
TNF
Inhibitors
Assessment Assessment in Early RA
Adalimumab
(Ada)
Disease control (ACR50): Ada<E
Disease Control (ACR50) when M-resistant: Ada>Ana, A≈Ada≈G≈I≈R≈T
Clinical response: Ada≈M
Radiologic response: TNF inhibitors >M
Functional capacity : Ada≈M
Certolizumab
pegol (C)
Not specif ically studied by AHRQ
Radiologic response: TNF inhibitors>M
Etanercept
(E)
Disease control (ACR50): E>A, Ada, Ana, I, R, T
Disease Control (ACR50) when M-resistant: E>Ana
Clinical response: E≈M
Radiologic response: TNF inhibitors>M
Speed of quality of life improv ement : E>M
Golimumab
(G)
Disease control (ACR50) when M-resistant: A≈Ada≈G≈I≈R≈T
Radiologic response: TNF inhibitors>M
Inf liximab (I)
Disease control (ACR50): I<E
Disease activ ity improvement: I<A
Quality of lif e: I<A, but judged not clinically important
Disease control (ACR50) when M-resistant: A≈Ada≈G≈I≈R≈T
Radiologic response: TNF inhibitors>M
Other Biologic Agents9,12-14 Medication Pharmacology Usual Dose and Route Adverse Effects and AHRQ
Comparative Safety
Abatacept
(A)
Recombinant CTLA4
molecule dimerized on
Ig f rame blocks T-cell
costimulation and
consequent Th17 cell
response and IL-6
8-10 mg/kg (500-1000 mg) at weeks
0, 2, 4 then monthly intrav enous, or
500-1000 mg intrav enous loading
dose, f ollowed by 125 mg
subcutaneous within a day, and then
once weekly. May also be giv en
subcutaneous without load
Inf usion reactions, inf ection.
Discontinuation rates and
serious adv erse ev ents A<I
Anakinra
(Ana)
Recombinant IL-1
receptor antagonist
100mg daily subcutaneous Injection site reactions,
inf ections, neutropenia. Ana
had highest risk of injection site
reactions. Withdrawals due to
lack of ef f icacy were
Ana≈Ada≈G≈I>All other
biologics
Rituximab
(R)
Chimeric monoclonal
CD20 f or B-cell
depletion
1000 mg in 2 inf usions, 2 weeks
apart intrav enous, repeating ev ery 4
to 8 months
Inf usion reactions, inf ection
Tocilizumab
(T)
Humanized monoclonal
IL-6 receptor blockade
8 mg/kg ev ery 4 weeks intrav enous Inf usion reactions, inf ection,
elev ated cholesterol
CTLA4= Cytotoxic T-Lymphocyte Antigen 4
9 Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-
modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625-639.
12 Isaacs JD. The changing face of rheumatoid arthritis: sustained remission for all? Nat Rev Immunol. 2010;10(8):605-611.
13 van Vollenhoven RF. Treatment of rheumatoid arthritis: state of the art in 2009. Nat Rev Rheumatol. 2009;5(10):531-541.
14 Donahue KE, Jonas D, Hansen RA, et al. Drug therapy for rheumatoid arthritis in adults: an update. Executive Summary. Compar ative
Effectiveness Review Number 55. AHRQ Publication No. 12-EHC025-1. Rockville, MD: Agency for Healthcare Research and Quality.
April 2012. http://www.effectivehealthcare.ahrq.gov/ehc/products/203/1042/CER55_ DrugTherapies-rheumatoidarthritis_execsumm.pdf. Accessed August 14, 2012.
AHRQ Comparison of Other
Biologic Agents14 Other Biologics Assessment
Abatacept (A) Disease control (ACR50): A<E
Disease activ ity Improvement: A>I
Quality of lif e: A<I, but judged not clinically important
Disease control (ACR50) when M-resistant: A≈Ada≈G≈I≈R≈T
Anakinra (Ana) Disease control (ACR50): Ana<E
Disease control (ACR50) when M-resistant: Ana<E, Ana<Ada
Rituximab (R) Disease control (ACR50): R<E
Disease control (ACR50) when M-resistant: A≈Ada≈G≈I≈R≈T
Tocilizumab (T) Disease control (ACR50): T<E
Disease control (ACR50) when M-resistant: A≈Ada≈G≈I≈R≈T
14 Donahue KE, Jonas D, Hansen RA, et al. Drug therapy for rheumatoid arthritis in adults: an update. Executive Summary. Comparative Effectiveness Review Number 55. AHRQ Publication No. 12-EHC025-1.
Rockville, MD: Agency for Healthcare Research and Quality. April 2012.
http://www.effec tivehealthcare.ahrq.gov/ehc /products/203/1042/CER55_DrugTherapi es-rheumatoidarthritis_execsumm.pdf . Accessed August 14, 2012.
Early RA Treatment Strategy9
9 Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-
modifying antirheumatic drugs and biologic agents in the treatment of
rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625-639.
HCQ= hydroxychloroquine sulfate MTX= methotrexate
Early RA Conceptual Model15
15 Finckh A, Liang MH, van Herckenrode CM, de Pablo P. Long-term impact of early treatment on radiographic
progression in rheumatoid arthritis: a meta-analysis.
Arthritis Rheum. 2006;55(6):864-872.
RCT= randomized, controlled trial
Early RA – ERA Trial16
16 Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343(22):1586- 1593.
Early/Very Early RA –
COMET Trial17
17 Emery P, Kvien TK, Combe B, et al. Combination etanercept and methotrexate provides better disease
control in very early (≤4 months) versus early rheumatoid
arthritis (>4 months and < 2 years): post hoc analysis from the COMET study. Ann Rheum Dis. 2012;71(6):989-992.
* P<0.05 for treatment effect
ETN= etanercept VERA= very early rheumatoid arthritis
ERA= early rheumatoid arthritis
Established RA Treatment9
LDA without Poor
Prognosis*
– DMARD monotherapy
– Add second agent
– Add or switch to anti-
TNF
» If ADR, sw itch to non-anti-
TNF biologic
» If no ADR, sw itch to non-
anti-TNF or other TNF
– Switch to alternate
biologic
LDA with Poor Prognosis,
or Moderate/Severe*
– DMARD monotherapy,
double or triple therapy
– Add DMARD, or
add/switch anti-TNF, or
abatacept or rituximab
» If ADR, sw itch to non-anti-
TNF biologic
» If no ADR, sw itch to non-anti-
TNF or other TNF
– Switch to alternate biologic
9 Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res
(Hoboken). 2012;64(5):625-639.
* Reassess at 3 month intervals except after non-TNF biologics assess at 6 month intervals
TNF Inhibitors: Meta-Analysis18
ACR50 Response – Infliximab trended better than control
– Etanercept significantly better than control
– Adalimumab significantly better than control
– Golimumab was no different than control
– Certolizumab significantly better than control
Discontinuation Due to ADR
– Infliximab significantly worse than control
– Etanercept significantly better than control
– Adalimumab significantly worse than control
– Golimumab was no different than control
– Certolizumab significantly worse than control
18 Aaltonen KJ, Virkki LM, Malmivaara A, Konttinen YT, Nordström DC, Blom M. Systematic review and meta-analysis of the efficacy and safety
of existing TNF blocking agents in treatment of rheumatoid arthritis. PLoS ONE. 2012;7(1):e30275.
Additional TNF Inhibitor
Considerations18
TNF inhibitor combination with methotrexate
vs methotrexate alone
– ACR50 RR 4.7, 95% CI 3.07-7.19
– Discontinuation RR 1.37, 95% CI 1.01-1.87
TNF inhibitor combination with methotrexate vs TNF inhibitor alone
– ACR50 RR 1.53, 95% CI 1.08-2.17
TNF inhibitor high dose vs normal dose
– ACR50 RR 1.02, 95% CI 0.9-1.15
18 Aaltonen KJ, Virkki LM, Malmivaara A, Konttinen YT, Nordström DC, Blom M. Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis. PLoS ONE. 2012;7(1):e30275.
How Is Failure Determined?9
At predefined intervals patients should
be assessed for
– Inadequate response (failure to improve disease activity index score)
– Progression of disease (worsening disease
activity index)
– Loss of efficacy (worsening disease after
improvement)
– Adverse events/medication safety
9 Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res
(Hoboken). 2012;64(5):625-639.
DMARD Failure
DRAG-RACE Study19 – Biologic naïve, failed DMARD
– Infliximab, etanercept 25mg or 50mg, or adalimumab, no
difference in disease activity at 4 to 6 weeks
ATTEST Study20 – Failed methotrexate
– Infliximab vs abatacept, at 1 year, similar DAS28-ESR score
change (-2.25 vs -2.88)
– Physical component scale (PCS) QOL improved with abatacept
1.93, 95% 0.2-3.84
AMPLE Study21 – Biologic naïve, failed DMARD
– Abatacept (subcutaneous) similar efficacy and better tolerated
than adalimumab
19 Hirano Y, Oishi Y, Yamauchi K, Mieno T. A comparative study of early clinical efficacy among three anti -TNF agents–DRAG RACE study. Ann Rheum Dis. 2012;71(suppl 3):666.
20 Schiff M, Keiserman M, Codding C, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III,
multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate
response to methotrexate. Ann Rheum Dis. 2008;67(8):1096-1103.
21 Schiff M, Fleischmann R, Weinblatt M, et al. Abatacept SC versus adalimumab on background methotrexate in RA: one
year results from the AMPLE study. Ann Rheum Dis. 2012;71(Suppl 3):60.
DMARD Failure,22,23 continued
AMPLE clinical outcomes AMPLE SF-36® outcomes
22 Fleischmann R, Schiff MH, Weinblatt ME, Maldonado MA, Massarotti EM, Yazici Y. Effects of subcutaneous abatacept or
adalimumab on remission and associated changes in physical function and radiographic outcomes: one year results from the AMPLE (abatacept versus adalimumab comparison in biologic-naïve RA subjects with background methotrexate) trial. Abstract
1340. Arthritis Rheum. 64(10):S577.
23 Fleischmann R, Weinblatt ME, Schiff MH, Khanna D, Furst D, Maldonado MA. Changes in patient reported outcomes in response to subcutaneous abatacept or adalimumab in rheumatoid arthritis: results from the AMPLE (abatacept versus
adalimumab comparison in biologic- naïve RA subjects with background methotrexate) trial. Abstract 1342. Arthritis Rheum.
64(10):S578.
Remission
Criteria SC Abatacept Adalimumab
DAS28-CRP ≤
2.6, n/m (%) 119/275
(43.3%) 112/267
(41.9%)
RAPID3 =
0-1.0 74/272 (27.2%) 66/263 (25.1%)
CDAI ≤ 2.8 65/277 (23.5%) 64/267 (24.0%)
SDAI ≤ 3.3 64/275 (23.3%) 66/266 (24.8%)
Boolean 6/275 (2.2%) 15/267 (5.6%)
Biologics for TNF Inhibitor Failure Meta-Analysis24
24 Schoels M, Aletaha D, Smolen JS, Wong JB. Comparative effectiveness and safety of biological treatment options after tumour necrosis factor α inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis. Ann
Rheum Dis. 2012;71(8):1303-1308.
Cost-Effectiveness in Varied Scenarios25,26
25 Schoels M, Wong J, Scott DL, et al. Economic aspects of treatment options in rheumatoid
arthritis: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2010;69(6):995-1003.
26 Fautrel B. Economic benefits of optimizing anchor therapy for rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 4):iv21-iv26. QALY= quality-adjusted life-year
Role of Specialty Pharmacy27
Contracting/Cost management
Authorization
– Obtain prior authorization
– Ensure step-up therapy
– Set dosing and quantity limits
– Select alternate agent(s)
– Provide case management services
Utilization
– Monitoring
– Adherence
Education
– Patient and provider
27 Shane R. Management of chronic disease in the 21st century: the emerging role of specialty pharmacies. Am J Health Syst Pharm. 2007;64(22)2382-2385.
Barriers to Treatment
Focus group study – Quebec28
– Primary care contact
» Lack of awareness – education needed on both sides
– Speed of specialist referral
» Education needed
» Access issues exist
– Barriers to treatment
» Communication lacking
» Education needed
– Inadequate resources
» Multidisciplinary approach needed
» Education needed
28 Bernatsky S, Feldman D, De Civita M, et al. Optimal care for rheumatoid arthritis: a focus group study. Clin Rheumatol. 2010;29(6):645-657.
Biologic Use over Time29
29 Zhang J, Xie F, Delzell ES, et al. Prevalence of biologic utilization over calendar time among Medicare beneficiaries with rheumatoid arthritis. Abstract 374. Arthritis Rheum. 64(10):S163.
IV vs SC Abatacept30
30 Genovese MC, Pacheco-Tena C, Covarrubias A. Subcutaneous abatacept: long-term data from the Acquire trial. Abstract 462. Arthritis Rheum. 64(10):S201.
IV= intravenous
Approaches to Improve
Disease Management
TICORA – TIght COntrol for RA Study31
– Randomized, assessed treat-to-target
– Intensive therapy – met rheumatologist monthly,
disease activity scored, joints injected with steroid,
medications adjusted on a protocol
– Routine care – every 3-month visit
– 18-month evaluation
» Remission 65% vs 16% (OR 9.7, 95% CI 3.9%-23.9%,
p<0.0001)
» Less erosion progression
» Total direct costs less in intensive group due to less
healthcare utilization
31 Grigor C, Capell H, Stirling A, et al. Effect of treatment strategy on tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364(9430):263-269.
Disease Management Program National PBM32
DTM Program Design
Consultation
– Education – lab values, pathophysiology, medication optimization, adherence
– Symptom, pain, and stress management
– Diet and exercise counseling
– Patient-provider communication
– Use of assistive devices and
home safety
– Financial assistance
Study Design and Results
Observational study
– DTM (ITT and completers)
– Specialty pharmacy
– Community pharmacy
14% enrolled in DTM
Proportion of days covered
– 0.89 DTM completers
– 0.83 DTM ITT
– 0.81 Specialty pharmacy
(p<0.001 vs completers)
– 0.6 community pharmacy (p<0.001 vs either DTM)
32 Stockl KM, Shin JS, Lew HC, et al. Outcomes of a rheumatoid arthritis disease therapy management program focusing on medication
adherence. Manage Care Pharm. 2010;16(8):593-604.
PBM= peripheral blood mononuclear cells ITT= intent to treat
Conclusions
RA is associated with significant morbidity and
mortality
Approach has transitioned from symptom
management to early diagnosis and definitive therapy
Treatment can limit disease progression and
disability
Specialty pharmacy can improve adherence
by providing oversight, intervention, and multidisciplinary insight
Thank You!