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!