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International Literature Search in Rheumatology. Vol. 6, Number 2 December 2011 In this issue: Highlights of the 2011 Annual Meeting of the American College of Rheumatology November 5-9, Chicago, IL. Table of Contents. Author(s) Poster / presentation #s Slides

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international literature search in rheumatology

International Literature Search in Rheumatology

Vol. 6, Number 2

December 2011

In this issue:Highlights of the 2011 Annual Meeting of theAmerican College of RheumatologyNovember 5-9, Chicago, IL

table of contents
Table of Contents

Author(s) Poster / presentation #s Slides

Hørslev-Petersen K 394 3 – 10

Genovese M 401 11 – 18

Genovese M 402 19 – 26

VanVollenhoven R 408 27 – 34

Yonemoto Y 1236 35 – 42

Yazici Y 124043 – 50

Bakker M 1695 51 – 58

O'Dell J 169659 – 66

Kaine JL 2190 67 – 74

Roussy J-P 2193 75 – 82

Meissner B 2197 83 – 90

Dirven L 2200 91 – 98

Raaschou P 2523 99 – 106

Galloway J 2524 107 – 114

Mercer L 2525 115 – 122

h rslev petersen k et al presented at acr 2011 poster 394

Adalimumab Added to Methotrexate andIntra-Articular Glucocorticoid Increases Remission Rates At One Year In Early,DMARD-Naïve Patients with Rheumatoid Arthritis - An Investigator-Initiated Randomized, Controlled, Double-Blinded Study

Hørslev-Petersen K, et al: Presented at ACR 2011;

Poster #394

adalimumab methotrexate intra articular glucocorticoid in dmard na ve early ra
Adalimumab + Methotrexate & Intra-articular Glucocorticoid in DMARD-naïve, Early RA
  • Objective: To assess the efficacy and safety of adding adalimumab (ADA) to methotrexate (MTX) and intra-articular glucocorticoid
  • Subjects: 180 DMARD-naïve RA patients, disease duration < 6 months
  • Methodology:
    • Subjects were randomized to MTX 7.5 mg weekly + ADA 40 mg every other week or MTX + placebo
    • All patients had triamcinolone injections into swollen joints at weeks 0, 4, 8, and 12, then every third month up to 12 months
    • If DAS28 > 3.2 at 3 months, sulfasalazine & hydroxychloroquine were added
    • Assessments: DAS28 (CRP), SDAI and ACR/EULAR remission criteria
    • Primary outcome: Frequency of DAS28 (CRP) < 3.2

Adapted from Hørslev-Petersen K, et al: Presented at ACR 2011; Poster #394

slide5
Adalimumab + Methotrexate & Intra-articular Glucocorticoid in DMARD-naïve, Early RA: Baseline Characteristics

Adapted from Hørslev-Petersen K, et al: Presented at ACR 2011; Poster #394

slide6
Adalimumab + Methotrexate & Intra-articular Glucocorticoid in DMARD-naïve, Early RA: Treatment Characteristics During the Study

Adapted from Hørslev-Petersen K, et al: Presented at ACR 2011; Poster #394

adalimumab added to mtx i a glucocorticoid das28 3 2 at 12 months
Adalimumab Added to MTX & I.A. Glucocorticoid: DAS28 < 3.2 at 12 Months

100%

p = 0.74

84

81

80%

60%

% of patients with DAS28 < 3.2

40%

20%

0%

MTX + Placebo

MTX + Adalimumab

Adapted from Hørslev-Petersen K, et al: Presented at ACR 2011; Poster #394

adalimumab added to mtx i a glucocorticoid remission
Adalimumab Added to MTX & I.A. Glucocorticoid: Remission

100%

MTX + Placebo

p = 0.059

MTX + Adalimumab

78

80%

p = 0.0017

64

63

p = 0.0235

p = 0.0095

60%

49

48

% of patients

38

40%

31

28

20%

0%

DAS28 < 2.6

SDAI < 3.3

ACR/EULARremission(28 joint)

ACR/EULARremission(40 joint)

Adapted from Hørslev-Petersen K, et al: Presented at ACR 2011; Poster #394

adalimumab methotrexate intra articularglucocorticoid in dmard na ve early ra conclusions
Adalimumab + Methotrexate & Intra-articularGlucocorticoid in DMARD-naïve, Early RA: Conclusions
  • In DMARD-naïve patients with early RA, excellent disease control was achieved by a targeted step-up strategy using methotrexate and intra-articular glucocorticoid injections
  • Addition of adalimumab to methotrexate and intra-articular glucocorticoid improved the remission rates considerably
  • The treatments were well tolerated

Adapted from Hørslev-Petersen K, et al: Presented at ACR 2011; Poster #394

adalimumab methotrexate intra articular glucocorticoid in dmard na ve early ra1
Adalimumab + Methotrexate & Intra-articular Glucocorticoid in DMARD-naïve, Early RA

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • This study used methotrexate doses of 20 mg per week, which reflects current practice in Canada; the use of intra-articular injections also applies to rheumatology standard-of-care in Canada
    • This study is, therefore, very applicable in our context
  • The only issue is availability of biologics in very early disease, but this study helps to corroborate the need for early treatment with biologics in RA

Commentary on Hørslev-Petersen K, et al: Presented at ACR 2011; Poster #394

slide11

One Year Efficacy and Safety Results of a Phase II Trial of Secukinumab in Patients with Rheumatoid Arthritis

Genovese MC, et al: Presented at ACR 2011;

Poster #401

phase ii study of secukinumab in rheumatoid arthritis
Phase II Study of Secukinumab in Rheumatoid Arthritis
  • Objective: To assess the efficacy and safety of secukinumab in patients with active RA despite stable MTX
  • Subjects: 237 adults with RA, taking MTX therapy
  • Methodology:
    • Subjects were randomized to receive monthly s.c. secukinumab25 mg, 75 mg, 150 mg, 300 mg or placebo
    • After Week 16, dose adjustments were made if necessary and placebo patients were switched to active therapy
    • Primary endpoint: ACR 20 at week 16 (previously reported)
    • Key efficacy measures evaluated in this analysis: Long-term results from week 24 to week 52
      • No placebo arm during this period: all patients were receiving secukinumab

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #401

secukinumab for rheumatoid arthritis study design
Secukinumab for Rheumatoid Arthritis: Study Design

Week 0 randomization N=237

25 mgN=54

75 mgN=49

150 mgN=43

300 mgN=41

pboN=50

Re-assignment at Week 16 based on ACR20 response: R and NR

N=47

N=47

N=43

N=38

N=45

Patients available for evaluation at Week 52

25/25

R=18

25/150

NR=27

75/75

R=23

75/150

NR=23

150/150

R=20

150/300

NR=23

300/300

R=21

300/300

NR=16

pbo/150

R=18

pbo/150

R=17

R: Responder; NR: Non-Responder; pbo: Placebo; N: Number of patients; Wk: Week; MTX: Methotrexate

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #401

secukinumab for rheumatoid arthritis acr and das28 responses
Secukinumab for Rheumatoid Arthritis: ACR and DAS28 Responses
  • Responders who remained on secukinumab 150 mg showed further improvement in ACR50 and ACR70 over time up to week 52
  • Placebo patients who were responders by week 16 also had high ACR50 and ACR70 response rates by week 52
  • DAS28 (CRP) reductions were sustained through week 52 in responders across dose groups, with lowest responses in those who remained on 25 mg throughout the trial

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #401

secukinumab for rheumatoid arthritis discontinuations
Secukinumab for Rheumatoid Arthritis: Discontinuations

50%

Overall study discontinuations

Discontinuations for AEs

Discontinuations for Unsatisfactory therapeutic effects

38.9

40%

30.0

30%

24.4

% of patients

22.4

20%

14.8

14.0

13.0

12.0

9.8

10%

8.2

7.0

6.0

4.9

4.1

0.0

0%

25 mg

75 mg

150 mg

300 mg

Total

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #401

secukinumab for rheumatoid arthritis adverse events
Secukinumab for Rheumatoid Arthritis: Adverse Events

100%

25 mg

75 mg

150 mg

300 mg

80%

Total

68.3

65.2

64.8

63.5

61.1

60%

% of patients

40%

34.8

33.3

31.9

28.3

26.1

20%

0%

Overall AEs

Infections / infestations

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #401

phase ii study of secukinumab in rheumatoid arthritis conclusions
Phase II Study of Secukinumab in Rheumatoid Arthritis: Conclusions
  • The primary efficacy endpoint was not achieved in this trial
  • ACR20 responders at Week 16 experienced maintenance or improvement of efficacy through week 52 with highest efficacy in patients who remained on secukinumab 150 mg throughout the trial
  • DAS28 and HAQ scores improved through week 52 in responders who remained on secukinumab 150 mg
  • Patients on secukinumab who were non-responders at week 18 did not gain much additional efficacy benefit through week 52 after dose escalation
  • Infection was the most frequently reported adverse event, with nasopharyngitis and pharyngitis reported most commonly
  • The rate of adverse events, including infections, was not dose dependent

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #401

phase ii study of secukinumab in rheumatoid arthritis1
Phase II Study of Secukinumab in Rheumatoid Arthritis

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • The success of biologic agents for the treatment of RA over the past 10 years has generated ongoing research to find drugs that target new pathways
  • A Phase 2 study previously reported that targeting IL-17 with secukinumab did not achieve its primary endpoint at week 16
  • This paper reports further data up to 1 year from that study and shows that although the group that did respond maintained their response, those who were non-responders did not improve with dose escalation
  • As reported elsewhere at this meeting, there are positive data treating spondyloarthropathies with this agent, particularly ankylosing spondylitis, but it remains to be seen whether targeting IL-17 will turn out to be a useful addition to treat RA

Commentary on Genovese MC, et al: Presented at ACR 2011; Poster #401

genovese mc et al presented at acr 2011 poster 402

Subcutaneous (SC) Abatacept (ABA) Versus Intravenous (IV) ABA in Patients (pts) with Rheumatoid Arthritis: Long-Term Data From the ACQUIRE (Abatacept Comparison of Sub[QU]cutaneous versus Intravenous in Inadequate Responders to MethotrexatE) Trial

Genovese MC, et al: Presented at ACR 2011;

Poster #402

subcutaneous vs intravenous abatacept in ra long term data acquire study
Subcutaneous vs. Intravenous Abataceptin RA: Long-term Data (ACQUIRE study)
  • Objective: To evaluate the efficacy and safety of the subcutaneous (SC) formulation of abatacept compared to the intravenous (IV) formulation over 24 months
  • Subjects:1372 patients from the ACQUIRE study
  • Methodology: Long-term extension (LTE) study of the ACQUIRE trial
    • In the initial 6-month study, SC abatacept (125 mg/week) and IV abatacept showed comparable safety and efficacy
    • After 6 months, patients could enter the LTE and receive SC abatacept 125 mg/week for an additional 18 months
    • LTE assessments: safety, immunogenicity, efficacy

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #402

acquire study long term extension baseline characteristics
ACQUIRE Study Long-term Extension: Baseline Characteristics

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #402

acquire study long term extension efficacy acr 20 50 70 over 24 months
ACQUIRE Study Long-term Extension: Efficacy – ACR 20/50/70 Over 24 Months

All patients switch to

SC abatacept

SC abatacept

100.0

IV abatacept switched to SC abatacept

80.0

ACR 20

60.0

Patients achieving ACR response (%)

ACR 50

40.0

ACR 70

20.0

0.0

0

29

85

141

253

365

449

533

617

729

15

57

113

169

Visit day

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #402

acquire study long term extension efficacy ldas and das28 remission
ACQUIRE Study Long-term Extension: Efficacy – LDAS and DAS28 Remission

All patients switch to

SC abatacept

SC abatacept

100.0

IV abatacept switched to SC abatacept

80.0

60.0

Patients achieving ACR response (%)

LDAS

40.0

DAS28-definedremission

20.0

0.0

0

29

85

141

253

365

449

533

617

729

15

57

113

169

Visit day

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #402

acquire study long term extension safety
ACQUIRE Study Long-term Extension: Safety

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #402

acquire study long term extension conclusions
ACQUIRE Study Long-term Extension: Conclusions
  • Over 24 months, subcutaneous abatacept showed acceptable safety, with high patient retention, similar to the IV experience
  • Efficacy was comparable between SC and IV groups
  • ACR and HAQ responses and DAS28 remission rates were maintained in the LTE

Adapted from Genovese MC, et al: Presented at ACR 2011; Poster #402

subcutaneous vs intravenous abatacept in ra long term results
Subcutaneous vs. Intravenous Abatacept in RA: Long-term Results

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • In this trial, patients with relatively longstanding RA (8 years) did well on either i.v. or s.c. abatacept, with similar retention, efficacy and safety in both groups
  • It remains to be seen whether patients who are currently receiving i.v .abatacept monthly will be interested in switching to weekly s.c. dosing, but this study does provide reassurance that, for those who wish to make the switch, the medication is effective

Commentary on Genovese MC, et al: Presented at ACR 2011; Poster #402

van vollenhoven rf et al presented at acr 2011 poster 408

Tofacitinib (CP-690,550), An Oral Janus Kinase Inhibitor, or Adalimumab Versus Placebo in Patients with Rheumatoid Arthritis on Background Methotrexate:A Phase 3 Study

van Vollenhoven RF, et al: Presented at ACR 2011;

Poster #408

tofacitinib vs adalimumab or placebo in ra patients on methotrexate
Tofacitinib vs. Adalimumab or Placebo in RA Patients on Methotrexate
  • Objective: To compare the efficacy and safety of tofacitinib to adalimumab and to placebo in active RA
  • Subjects: 717 patients with active RA and inadequate response to methotrexate
  • Methodology:
    • Subjects were randomized (4:4:4:1:1 ratio) to:
      • Tofacitinib 5 mg BID SC Q2W);
      • Tofacitinib 10 mg BID SC Q2W;
      • Adalimumab 40 mg SC Q2W;
      • Placebo  tofacitinib 5 mg BID SC Q2W; or
      • Placebo  tofacitinib 10 mg BID SC Q2W
    • Efficacy assessments: ACR response, HAQ-DI, DAS28
    • Safety was also evaluated

Adapted from van Vollenhoven RF, et al: Presented at ACR 2011; Poster #408

tofacitinib vs adalimumab or placebo in ra acr20 responses at month 6
Tofacitinib vs. Adalimumab or Placebo in RA: ACR20 Responses at Month 6

100%

80%

60%

52.6

51.5

% of patients

47.2

40%

28.3

20%

0%

Adalimumab 40 mg

Tofacitinib 5 mg

Tofacitinib 10 mg

Placebo

All comparisons of active therapies vs. placebo were statistically significant (p<0.001)

Adapted from van Vollenhoven RF, et al: Presented at ACR 2011; Poster #408

tofacitinib vs adalimumab or placebo in ra patients das28 remission at month 6
Tofacitinib vs. Adalimumab or Placebo in RA Patients: DAS28 Remission at Month 6

14%

12.5

12%

10%

8%

7.3

% of patients

6.2

6%

4%

2%

1.1

0%

Adalimumab 40 mg

Tofacitinib 5 mg

Tofacitinib 10 mg

Placebo

All comparisons of active therapies vs. placebo were statistically significant (p<0.05)

Adapted from van Vollenhoven RF, et al: Presented at ACR 2011; Poster #408

tofacitinib vs adalimumab or placebo in ra patients mean haq change at month 6
Tofacitinib vs. Adalimumab or Placebo in RA Patients: Mean HAQ Change at Month 6

Adalimumab 40 mg

Tofacitinib 5 mg

Tofacitinib 10 mg

Placebo

0

-0.1

-0.2

-0.24

-0.3

Change in HAQ Score from baseline

-0.4

-0.5

-0.49

-0.55

-0.6

-0.61

-0.7

All comparisons of active therapies vs. placebo were statistically significant (p<0.0001)

Adapted from van Vollenhoven RF, et al: Presented at ACR 2011; Poster #408

tofacitinib vs adalimumab or placebo in ra patients on methotrexate adverse events
Tofacitinib vs. Adalimumab or Placebo in RA Patients on Methotrexate: Adverse Events

Adapted from van Vollenhoven RF, et al: Presented at ACR 2011; Poster #408

tofacitinib vs adalimumab or placebo in ra patients on methotrexate conclusions
Tofacitinib vs. Adalimumab or Placebo in RA Patients on Methotrexate: Conclusions
  • Tofacitinib demonstrated rapid, significant, and clinically meaningful reductions in signs and symptoms of RA and improvements in physical function
  • No new tofacitinib safety signals were detected
  • Efficacy results with tofacitinib and adalimumab (both given on MTX background) were similar

Adapted from van Vollenhoven RF, et al: Presented at ACR 2011; Poster #408

tofacitinib vs adalimumab or placebo in ra patients on methotrexate1
Tofacitinib vs. Adalimumab or Placebo in RA Patients on Methotrexate

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • Tofacitinib will be a useful addition to our armamentarium for the treatment of RA, especially as it is an oral medication
  • The SAEs are, however, of some concern; larger studies should be carried out to further assess this

Commentary on van Vollenhoven RF, et al: Presented at ACR 2011; Poster #408

direct comparison of four biologics in biologic na ve rheumatoid arthritis patients

Direct Comparison of Four Biologics in Biologic-naïve Rheumatoid Arthritis Patients

Yonemoto Y, et al: Presented at ACR 2011;Poster #1236

direct comparison of four biologics in biologic na ve ra
Direct Comparison of Four Biologics in Biologic-naïve RA
  • Objective: To compare treatment response to four biologics in biologic-naïve RA patients in a real-life, clinical setting
  • Subjects: 142 biologic-naïve RA patients who were started on a biologic
    • Infliximab (n=37)
    • Etanercept (n=39)
    • Tocilizumab (n=27)
    • Adalimumab (n=39)
  • Methodology:
    • A number of variables were analyzed at baseline and at six months: ESR, CRP, MMP-3, SJC/TJC, DAS28-ESR
    • Drug survival rate was also assessed

Adapted from Yonemoto Y, et al: Presented at ACR 2011; Poster #1236

direct comparison of four biologics baseline characteristics
Direct Comparison of Four Biologics: Baseline Characteristics

Adapted from Yonemoto Y, et al: Presented at ACR 2011; Poster #1236

direct comparison of four biologics das28 esr scores at 6 months
Direct Comparison of Four Biologics:DAS28-ESR Scores at 6 Months

6.0

5.0

4.0

3.0

DA28-ESR

2.0

1.0

0

Biologic:

IFX

ETN

TCZ

ADA

Baseline DAS28-ESR:

4.9

4.8

5.5

4.8

Adapted from Yonemoto Y, et al: Presented at ACR 2011; Poster #1236

direct comparison of four biologics mmp 3 at 6 months
Direct Comparison of Four Biologics: MMP-3 at 6 Months

1200.0

1000.0

800.0

MMP-3 (ng/ml)

600.0

400.0

200.0

0.0

Biologic:

IFX

ETN

TCZ

ADA

Baseline MMP-3 (ng/mL):

275.2

241.0

315.4

286.0

Adapted from Yonemoto Y, et al: Presented at ACR 2011; Poster #1236

direct comparison of four biologics drug survival rates at 6 months
Direct Comparison of Four Biologics: Drug Survival Rates at 6 Months

100

100%

92

89

89

80%

60%

% still taking drug at 6 months

40%

20%

0%

Infliximab

Etanercept

Tocilizumab

Adalimumab

No significant difference between biologics in drug survival rates

Adapted from Yonemoto Y, et al: Presented at ACR 2011; Poster #1236

comparison of four biologics in biologic na ve ra conclusions
Comparison of Four Biologics in Biologic-naïve RA: Conclusions
  • In this study, there was a larger fall in MMP-3 with tocilizumab than with the other two agents
  • The study suggests that tocilizumab may provide therapeutic efficacy at least comparable to TNF inhibitors in biologic-naïve RA patients

Adapted from Yonemoto Y, et al: Presented at ACR 2011; Poster #1236

direct comparison of four biologics in biologic na ve ra1
Direct Comparison of Four Biologics in Biologic-naïve RA

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • This confirms that all the TNF inhibitors are equally clinically effective and that tocilizumab is at least as effective in biologic-naïve RA patients

Commentary on Yonemoto Y, et al: Presented at ACR 2011; Poster #1236

slide43

Comparative Efficacy and Tolerability of Biologic Therapies in Early Rheumatoid Arthritis Utilizing a Bayesian Approach

Yazici Y, et al: Presented at ACR 2011;Poster #1240

comparative efficacy and tolerability of biologic therapies in ra
Comparative Efficacy and Tolerability of Biologic Therapies in RA
  • Objective: To determine the relative efficacy and tolerability of biologic agents approved for the treatment of MTX-naïve early RA
  • Methodology: Agents were compared using an indirect approach (mixed treatment comparison [MTC])
    • Systematic literature review identified RCTs that measured efficacy and safety endpoints in MTX-naïve, early RA with:
      • Abatacept, adalimumab, etanercept, golimumab, and infliximab
    • Assessments: ACR20/50/70, DAS28 remission, SAEs, serious infections and withdrawals at 1 year

Adapted from YaziciY, et al: Presented at ACR 2011; Poster #1240

comparative efficacy of biologic therapies in ra efficacy measures
Comparative Efficacy of Biologic Therapies in RA: Efficacy Measures

Adapted from Yazici Y, et al: Presented at ACR 2011; Poster #1240

comparative efficacy of biologic therapies in ra odds ratios for acr responses and das28 remission
Comparative Efficacy of Biologic Therapies in RA: Odds Ratios for ACR Responses and DAS28 Remission

Fixed-effects model

Odds Ratios (Log Scale)

Random-effects model

0.1

1

10

100

ETN 50mg

ETN 50mg

ETN 50mg

ETN 50mg

3.02

ADA 40mg

ADA 40mg

ADA 40mg

ADA 40mg

1.60

ACR 70

ACR 50

DAS-R

ACR 20

ABA 10mg/kg

ABA 10mg/kg

ABA 10mg/kg

ABA 10mg/kg

1.96

GOL 50mg

GOL 50mg

GOL 50mg

GOL 50mg

1.64

INF 3mg/kg

INF 3mg/kg

INF 3mg/kg

INF 3mg/kg

1.44

2.59

2.37

2.52

1.92

2.19

2.84

1.84

1.98

2.34

1.60

1.63

1.71

1.53

1.80

1.77

Adapted from Yazici Y, et al: Presented at ACR 2011; Poster #1240

comparative tolerability of biologic therapies in ra serious infections and serious aes
Comparative Tolerability of Biologic Therapies in RA: Serious Infections and Serious AEs

Fixed-effects model

Odds Ratios vs. Placebo + MTX

Random-effects model

0.01

0.1

10

100

1

ETN 50mg

0.94

ABA 10mg/kg

SeriousInfections

0.99

GOL 50mg

0.91

INF 3mg/kg

1.32

ETN 50mg

0.59

ADA 40mg

1.26

SeriousAE

ABA 10mg/kg

0.45

GOL 50mg

0.63

INF 3mg/kg

2.97

Adapted from Yazici Y, et al: Presented at ACR 2011; Poster #1240

comparative tolerability of biologic therapies in ra discontinuations
Comparative Tolerability of Biologic Therapies in RA: Discontinuations

Fixed-effects model

Odds ratios vs. Placebo + MTX

Random-effects model

0.01

0.1

10

100

1

ETN 50mg

0.57

ADA 40mg

0.61

AnyWithdrawal

ABA 10mg/kg

0.90

GOL 50mg

0.76

INF 3mg/kg

0.85

ETN 50mg

0.78

ADA 40mg

1.71

Withdrawaldue to AE

ABA 10mg/kg

0.70

GOL 50mg

2.66

INF 3mg/kg

3.32

Adapted from Yazici Y, et al: Presented at ACR 2011; Poster #1240

comparative efficacy of biologic therapies in ra conclusions
Comparative Efficacy of Biologic Therapies in RA: Conclusions
  • In general, all biologic agents used in MTX-naïve early RA demonstrated similar efficacy and tolerability
    • Except for infliximab, which appeared to have less favorable efficacy and tolerability
  • For specific outcomes studied, etanercept and abatacept were not significantly different from each other and were the only biologics that did not demonstrate a significantly decreased likelihood of efficacy or tolerability compared with any of the other agents

Adapted from Yazici Y, et al: Presented at ACR 2011; Poster #1240

comparative efficacy and tolerability of biologic therapies in ra1
Comparative Efficacy and Tolerability of Biologic Therapies in RA

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • All of the biologics analyzed in this Bayesian analysis were comparable with regards to efficacy and safety in an ERA, MTX-naïve population
  • However, only etanercept and abatacept did not show any decreased likelihood of efficacy or tolerability compared to other agents

Commentary on Yazici Y, et al: Presented at ACR 2011; Poster #1240

bakker mf et al presented at acr 2011 oral presentation 1695

Double-Blind Randomized CAMERA-II Trial: Better Control of Disease and Erosive Joint Damage with Inclusion of Low-Dose Prednisone Into a MTX-Based Tight Control Strategy for Early Rheumatoid Arthritis

Bakker MF, et al: Presented at ACR 2011;Oral presentation #1695

low dose prednisone with mtx based tight control in early ra camera ii study
Low-dose Prednisone with MTX-based Tight Control in Early RA: CAMERA II Study
  • Objective:To evaluate efficacy and safety of 10 mg/day prednisone from the start of treatment with a methotrexate (MTX)-based, tight-control strategy for early RA
  • Subjects: 236 patients with early RA (<1 year)
  • Methodology: 2-year, prospective randomized, placebo-controlled, double-blind, multi-centre study
    • Subjects were randomized to a MTX-based tight control strategy with either prednisone (MTX-pred) or placebo (MTX-plac)
    • MTX treatment was tailored to the individual patient, aiming for remission
    • Primary endpoint: radiographic erosive joint damage after 2 years

Adapted from Bakker MF, et al: Presented at ACR 2011; Oral presentation #1695

slide53
Low-dose Prednisone with MTX-based Tight Control in Early RA: Erosion Score After 2 Years (Cumulative Probability Plot)

MTX-placebo

MTX-prednisone

40

Medianerosion score at 2yearsless in the MTX+prodstrategy, p=0.02

20

67%

78%

0

0

60

80

100

Adapted from Bakker MF, et al: Presented at ACR 2011; Oral presentation #1695

low dose prednisone with mtx based tight control in early ra sustained remission
Low-dose Prednisone with MTX-based Tight Control in Early RA: Sustained Remission

100%

p = 0.09

80%

72

61

60%

% of patients

40%

20%

0%

MTX + prednisone

MTX + placebo

Adapted from Bakker MF, et al: Presented at ACR 2011; Oral presentation #1695

low dose prednisone with mtx based tight control in early ra need for biologic therapy
Low-dose Prednisone with MTX-based Tight Control in Early RA: Need for Biologic Therapy

100%

80%

60%

% of patients requiring biologic

p< 0.001

36

40%

20%

14

0%

MTX + prednisone

MTX + placebo

Adapted from Bakker MF, et al: Presented at ACR 2011; Oral presentation #1695

low dose prednisone with mtx based tight control in early ra adverse events
Low-dose Prednisone with MTX-based Tight Control in Early RA: Adverse Events

Adapted from Bakker MF, et al: Presented at ACR 2011; Oral presentation #1695

low dose prednisone in early ra conclusions from the camera ii study
Low-dose Prednisone in Early RA:Conclusions from the CAMERA II Study
  • Inclusion of low-dose prednisone from the start into a two-year MTX-based tight control treatment strategy for early RA:
    • Increases effectiveness (i.e., disease activity variables)
    • Improves outcome (i.e., erosive joint damage)
    • Does not increase toxicity
    • Reduces the need for (early) treatment with biologics

Adapted from Bakker MF, et al: Presented at ACR 2011; Oral presentation #1695

low dose prednisone with mtx based tight control in early ra
Low-dose Prednisone with MTX-based Tight Control in Early RA

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • In this study, a methotrexate-based, treat-to-target approach in an early RA population showed that adding low dose prednisone had a “biologic sparing” effect
  • The addition of prednisone appeared to be disease modifying, without added side effects
  • However, the use of long-term corticosteroids may not be a widely accepted strategy

Commentary on Bakker MF, et al: Presented at ACR 2011; Oral presentation #1695

slide59

Validation of Methotrexate First Strategy in Early Rheumatoid Arthritis:A Randomized, Double-Blind, 2-Year Trial

O'Dell JR, et al: Presented at ACR 2011;Oral presentation #1696

validation of methotrexate first strategy
Validation of Methotrexate First Strategy
  • Objective: To compare initial methotrexate (MTX) therapy with initial MTX-based combination therapy in early RA
  • Subjects: 755 patients with early RA and a poor prognosis
  • Methodology:
    • Subjects were randomized to initial MTX or immediate combination therapy (MTX/etanercept or MTX/SSZ/HCQ)
    • Primary efficacy assessment: DAS28

Adapted from O'Dell JR, et al: Presented at ACR 2011; Oral presentation #1696

validation of methotrexate first strategy proportion of mtx subjects requiring step up
Validation of Methotrexate First Strategy: Proportion of MTX Subjects Requiring Step-up

28%

72%

Required step-up

(DAS28 > 3.2)

Remained on MTX

Monotherapy

(DAS28 ≤ 3.2)

Adapted from O'Dell JR, et al: Presented at ACR 2011; Oral presentation #1696

validation of methotrexate first strategy mean das28 to week 102
Validation of Methotrexate First Strategy: Mean DAS28 to Week 102

7

SE

IE

6

ST

IT

5

4

Primary Analysis: Weeks 48 to 102

Comparison p-value

Groups (IE, IT, SE, ST) 0.55

Time (I = S) 0.37

Trt (ETN > TT) 0.18

DAS28

3

Step-up to MultipleDMARD at Week24 if DAS28 ≥ 3.2

2

1

0

Week 0

(755)

Week 12

(661)

Week 24

(646)

Week 36

(601)

Week 48

(582)

Week 60

(522)

Week 72

(518)

Week 84

(508)

Week 96(485)

Week 102

(476)

Adapted from O'Dell JR, et al: Presented at ACR 2011; Oral presentation #1696

validation of methotrexate first strategy radiographic progression cumulative probability
Validation of Methotrexate First Strategy:Radiographic Progression (Cumulative Probability)

100

Initial Etanercept

Initial Triple

80

Step-up Etanercept

Step-up Triple

60

Week 102 Change from Baseline (%)

40

20

0

-20

0

10

20

30

40

50

60

70

80

90

100

Cumulative probability

Adapted from O'Dell JR, et al: Presented at ACR 2011; Oral presentation #1696

validation of methotrexate first strategy mtx only patients achieving das28 reduction thresholds
Validation of Methotrexate First Strategy:MTX-only Patients Achieving DAS28 Reduction Thresholds

70

DAS > 2.4

DAS > 1.8

60

DAS > 1.2

50

40

Percentage of patients (%)

30

20

10

0

Week 12

Week 24

Adapted from O'Dell JR, et al: Presented at ACR 2011; Oral presentation #1696

validation of methotrexate first strategy conclusions
Validation of Methotrexate First Strategy: Conclusions
  • These data validate the oft-recommended strategy of starting with MTX monotherapy
  • If this is done, approximately 30% of patients will not need combination therapy and the 70% who need add-on therapy will be:
    • Clinically indistinguishable from those that received immediate combination therapy 3 months after step-up
    • Radiographically indistinguishable at 2 years

Adapted from O'Dell JR, et al: Presented at ACR 2011; Oral presentation #1696

validation of methotrexate first strategy1
Validation of Methotrexate First Strategy

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • In this study, one-third of patients did well on methotrexate monotherapy
    • This has significant implications for cost avoidance
  • The main message of the study is that if you treat to target, patients do well

Commentary on O'Dell JR, et al: Presented at ACR 2011; Oral presentation #1696

kaine jl et al presented at acr 2011 poster 2190

SC Abatacept Is Effective and Well Tolerated with Low Immunogenicity Following Temporary Withdrawal and Reintroduction in the ALLOW LTE (Evaluation of ABA Administered SubcutaneousLy in AduLts With Active RA: Impact of Withdrawal and Reintroduction)

Kaine JL, et al: Presented at ACR 2011;Poster #2190

temporary withdrawal reintroduction of abatacept in ra
Temporary Withdrawal & Reintroduction of Abatacept in RA
  • Objective: To assess the impact of withdrawal and re-introduction of subcutaneous (SC) abatacept (ABA) on safety, immunogenicity and efficacy
  • Subjects: 150 patients with mild-to-moderate RA on MTX, from the long-term extension of the ALLOW study
  • Methodology:
    • The ALLOW study consisted of four phases:
      • Period I: 3 months, open-label SC ABA 125 mg Q2W
      • Period II: 3 months, randomized to SC ABA 125 mg Q2W or placebo
      • Period III: 3 months, open-label SC ABA 125 mg Q2W
      • Long-term extension: 6 months open-label SC ABA 125 mg Q2W
    • This analysis assessed efficacy, safety, and immunogenicity through15 months

Adapted from Kaine JL, et al: Presented at ACR 2011; Poster #2190

temporary withdrawal reintroduction of abatacept in ra study design
Temporary Withdrawal & Reintroduction of Abatacept in RA: Study Design

Introduction Phase

Period I: SC open-label12 weeks

Withdrawal Phase

Period II: double-blind12 weeks

Re-introduction Phase

Period III: SC open-label12 weeks

IV loading dose:placebo (blinded)

Respondersrandomized

Loading doseIV abatacept

Day 1

SC abatacept + MTX†n=40

SC abatacept + MTXn=40

Long-term extension:

SC open-label

IV abatacept

SC abatacept + MTXn=167

SC abatacept + MTXn=79

SC placebo + MTX†n=80

IV loading dose: abataceptor placebo (blinded)

Month 6 (Day 169)

Primary endpoint:

Immunogenicity

Secondary endpoints:

Safety

Efficacy

Month 3 (Day 85)

Month 9 (Day 253)

Primary endpoint:

Immunogenicity

Secondary endpoints:

Safety

Efficacy

Adapted from Kaine JL, et al: Presented at ACR 2011; Poster #2190

temporary withdrawal reintroduction of abatacept in ra efficacy das28
Temporary Withdrawal & Reintroduction of Abatacept in RA: Efficacy (DAS28)

Period I:IntroductionSC ABA, N=167

Period II:WithdrawalSC ABA, N=40vs. PBO, N=80

Period III:Re-IntroductionSC ABA, N=40SC PBO, N=79

Long-term extension:

SC ABA open-labelPeriod I NRs, N=37

Period III completers, N=113

(SC ABA, N=39; SC PBO, N=74)

0.5

Studyvisit day

85

169

253

449

0.0

Period I NR

-0.5

Period II SC ABA

Period II SC PBO

-1.0

DAS28 mean change from baseline

-1.5

-2.0

-2.5

Adapted from Kaine JL, et al: Presented at ACR 2011; Poster #2190

temporary withdrawal reintroduction of abatacept safety
Temporary Withdrawal & Reintroduction of Abatacept: Safety

Adapted from Kaine JL, et al: Presented at ACR 2011; Poster #2190

temporary withdrawal reintroduction of abatacept immunogenicity
Temporary Withdrawal & Reintroduction of Abatacept: Immunogenicity

Overall

2.8%

Period I NR

2.8%

Period II SC ABA

2.6%

Period II placebo

2.9%

0%

20%

40%

60%

80%

100%

% of patients with positive immunogenicity

NR: Non-responders; SC ABA: subcutaneous abatacept

Adapted from Kaine JL, et al: Presented at ACR 2011; Poster #2190

temporary withdrawal reintroduction of abatacept allow study conclusions
Temporary Withdrawal & Reintroduction of Abatacept (ALLOW study): Conclusions
  • In ALLOW, 3-month interruption and subsequentre-introduction of SC abatacept had no adverse impact on safety, immunogenicity or efficacy over15 months
  • This treatment pattern was well-tolerated by the patients continuing treatment in the LTE

Adapted from Kaine JL, et al: Presented at ACR 2011; Poster #2190

temporary withdrawal reintroduction of abatacept in ra1
Temporary Withdrawal & Reintroduction of Abatacept in RA

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • Patients frequently ask if they can safely stop their medications
  • Rheumatologists have been leery of advising this, in part because of experiences and published data from gold withdrawal studies where 2/3 of patients flared within a year of ceasing drug, as well as poor response rates upon reintroduction of the medication
  • In this study, a 3-month interruption and subsequent reintroduction of s.c. abatacept recaptured efficacy and was not associated with immunogenicity
  • This has important real-life implications for patients and their rheumatologists when drug interruption is required

Commentary on Kaine JL, et al: Presented at ACR 2011; Poster #2190

use of disease modifying anti rheumatic drugs for rheumatoid arthritis in quebec canada

Use of Disease-Modifying Anti-Rheumatic Drugs for Rheumatoid Arthritis in Quebec, Canada

Roussy J-P, et al: Presented at ACR 2011;Poster #2193

patterns of dmard use for ra in quebec
Patterns of DMARD Use for RA in Quebec
  • Objectives:
    • To describe the characteristics of RA subjects in Quebec
    • To evaluate trends in DMARD use
    • To assess potential factors associated with DMARD use in newly diagnosed RA
  • Subjects: 37,399 subjects from Quebec public healthcare system databases between January 1, 2002 and December 31, 2008
  • Methodology: Analyses included:
    • Patient characteristics
    • Patterns of DMARD use and their evolution over time
    • Probability and correlates of DMARD initiation at 12 months

Adapted from Roussy J-P, et al: Presented at ACR 2011; Poster #2193

treatment patterns for ra in quebec
Treatment Patterns for RA in Quebec

50.0%

45.0%

40.0%

35.0%

30.0%

Percentage of subjects

25.0%

No treatment

20.0%

Non-DMARD only

15.0%

DMARD - any

DMARD-t

10.0%

DMARD-b (+/- DMARD-t)

5.0%

0.0%

Nov.

2002

Nov.

2003

Nov.

2004

Nov.

2005

Nov.

2006

Nov.

2007

Nov.

2008

DMARD-t: Traditional DMARD; DMARB-b: Biologic DMARD

Adapted from Roussy J-P, et al: Presented at ACR 2011; Poster #2193

time from diagnosis to initiation of any dmard by specialty
Time from Diagnosis to Initiation of Any DMARD, by Specialty

1.0

Censored

Other specialist

0.8

GP

Internist

0.6

Survival probability

Rheumatologist

0.4

0.2

Log rank, p<0.0001

0.0

0

500

1000

1500

2000

2500

Survival days

Adapted from Roussy J-P, et al: Presented at ACR 2011; Poster #2193

predictors of dmard use for ra in quebec multivariate analysis 1 of 2
Predictors of DMARD Use for RA in Quebec: Multivariate Analysis (1 of 2)

Adapted from Roussy J-P, et al: Presented at ACR 2011; Poster #2193

predictors of dmard use for ra in quebec multivariate analysis 2 of 2
Predictors of DMARD Use for RA in Quebec: Multivariate Analysis (2 of 2)

Adapted from Roussy J-P, et al: Presented at ACR 2011; Poster #2193

patterns of dmard use for ra in quebec conclusions
Patterns of DMARD Use for RA in Quebec: Conclusions
  • From 2002 to 2008, the use of RA treatment in Quebec has evolved
  • Despite indications that practice is moving toward earlier and more aggressive management of the disease, initiation of DMARD therapies still appears sub-optimal
  • Improving access to rheumatologists could be an area of focus in order to enhance the quality of RA care

Adapted from Roussy J-P, et al: Presented at ACR 2011; Poster #2193

patterns of dmard use for ra in quebec1
Patterns of DMARD Use for RA in Quebec

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • These findings further highlight the need for earlier access to rheumatologists for patients with RA

Commentary on Roussy J-P, et al: Presented at ACR 2011; Poster #2193

meissner b et al presented at acr 2011 poster 2197

Switching of Biologic Disease-Modifying Antirheumatic Drugs During the First Year in Patients with Rheumatoid Arthritis in aReal-World Setting

Meissner B, et al: Presented at ACR 2011;Poster #2197

switching biologics for ra in a real world setting
Switching Biologics for RA in aReal-World Setting
  • Objective: To characterize biologic switching in a real-world RA population in the first year following initiation of therapy
  • Subjects: 9,757 RA patients newly initiated on abatacept, etanercept, infliximab, or adalimumab
  • Methodology: Observational, retrospective study
    • Data were from American administrative medical and pharmacy claims from 2004 through 2010
    • Switching of biologic therapy was characterized during the 12-month period following biologic initiation
    • Analyses were conducted to examine the characteristics of switchers versus non-switchers

Adapted from Meissner B, et al: Presented at ACR 2011; Poster #2197

proportion of ra patients switching biologics in the first year
Proportion of RA Patients Switching Biologics in the First Year

100%

80%

60%

% of patients

40%

20%

8.9

8.5

7.8

5.2

2.0

0%

Abatacept

Adalimumab

Etanercept

Infliximab

Overall

Adapted from Meissner B, et al: Presented at ACR 2011; Poster #2197

which type of biologic was used as the 2nd agent
Which Type of Biologic Was Used As the 2nd Agent?

Non-anti-TNF biologic

Anti-TNF biologic

100%

10.0

55.4

5.2

90.0

94.8

80%

60%

% of patients

44.6

40%

20%

8.5

0%

Adalimumab

Etanercept

Infliximab

First Biologic Agent

Adapted from Meissner B, et al: Presented at ACR 2011; Poster #2197

proportion of patients requiring switch to 3rd biologic within 1st year
Proportion of Patients Requiring Switch to 3rd Biologic Within 1st Year

100%

80%

60%

% of patients

40%

18.1

20%

12.9

12.8

6.0

0%

Abatacept

Adalimumab

Etanercept

Infliximab

Second Biologic

Adapted from Meissner B, et al: Presented at ACR 2011; Poster #2197

healthcare utilization differences between switchers and nonswitchers prior to biologic initiation
Healthcare Utilization Differences Between Switchers and Nonswitchers (Prior to Biologic Initiation)

Hospitalizations

Monthly Healthcare Costs

$1,500

100%

p< 0.001

p = 0.015

$1,200

80%

1,025

$900

60%

796

% of patients

$ US

$600

40%

$300

20%

9.5

7.2

0%

$0

Switchers

Switchers

Nonswitchers

Nonswitchers

Adapted from Meissner B, et al: Presented at ACR 2011; Poster #2197

switching biologics for ra in a real world setting conclusions
Switching Biologics for RA in a Real-World Setting: Conclusions
  • Less than 10% of RA patients who initiated therapy on adalimumab, etanercept, infliximab or abatacept switched to a second biologic in their first year of therapy
  • Switching was associated with significantly more hospitalizations and healthcare costs than not switching
  • Further studies are required to determine why abatacept-treated patients had a lower frequency of switching than the other three biologics studied

Adapted from Meissner B, et al: Presented at ACR 2011; Poster #2197

switching biologics for ra in a real world setting1
Switching Biologics for RAin a Real-World Setting

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • Overall, in this database, switching biologics was rather low in the first year after initiation (<10%)
  • Abatacept was the least likely biologic to generate a switch and the reason for this is unclear
  • One might presume that either this drug demonstrated increased sustainability or, alternatively, might have been selected as a first choice to avoid anti-TNF’s, thereby making it less likely to switch to an anti-TNF if a change was needed

Commentary on Meissner B, et al: Presented at ACR 2011; Poster #2197

slide91

Eight Year Results of Disease Activity Steered Treatment in a Large Recent Rheumatoid Arthritis Cohort:Clinical and Radiological Outcomes

Dirven L, et al: Presented at ACR 2011;Poster #2200

8 year results of a das steered treatment study best
8-Year Results of a DAS-steered Treatment Study (BeSt)
  • Objective: To compare 8-year outcomes of four dynamic DAS steered treatment strategies (from the BeSt study)
  • Subjects: 508 patients with recent onset rheumatoid arthritis (RA)
  • Methodology:
    • Subjects were randomized to one of four treatment strategies:
      • Sequential monotherapy,
      • Step-up combination therapy,
      • Initial combination with prednisone, or
      • Initial combination with infliximab.
    • Every three months, treatment adjustments were made based on DAS measurements
    • Assessments included HAQ and progression of joint damage

Adapted from Dirven L, et al: Presented at ACR 2011; Poster #2200

best study treatment groups
BeSt Study: Treatment Groups

Group 1:

Sequential

Monotherapy

MTX

SSZ

LEF

MTX

+ Biologic

Group 2:

Step-up

Therapy

MTX

MTX

+ SSZ

MTX

+ SSZ + HCQ

MTX + SSZ

+ HCQ + PRED

MTX

+ Biologic

Group 3:

Initial combo with

prednisone

MTX

+ SSZ + PRED

MTZ

+ CSA + PRED

MTX

+ Biologic

Group 4:

Initial combo

with infliximab

MTX

+ Biologic

SSZ

LEF

MTX

+ CSA + PRED

1.

2.

3.

4.

5.

Adapted from Dirven L, et al: Presented at ACR 2011; Poster #2200

8 year results of the best study patient disposition
8-Year Results of the BeSt Study:Patient Disposition

Adapted from Dirven L, et al: Presented at ACR 2011; Poster #2200

8 year results of the best study mean haq over time
8-Year Results of the BeSt Study:Mean HAQ Over Time

1.6

Sequential monotherapy

Step-up combination therapy

Initial combination with prednisone

1.4

Initial combination with infliximab

1.2

1.0

HAQ Score

0.8

0.6

0.4

0.2

0

0

1

2

3

4

5

6

7

8

Year

*p < 0.05 for Group 4 vs. Group 2

Adapted from Dirven L, et al: Presented at ACR 2011; Poster #2200

8 year results of the best study radiologic progression
8-Year Results of the BeSt Study: Radiologic Progression

20

Year 8

Year 7

Year 6

16

Year 5

Year 4

Year 3

Year 2

12

Year 1

Mean SHS progression

8

4

0

Sequentialmonotherapy

Step-uptherapy

Initial combinationwith prednisone

Initial combinationwith infliximab

Adapted from Dirven L, et al: Presented at ACR 2011; Poster #2200

8 year results of the best study conclusions
8-Year Results of the BeSt Study: Conclusions
  • Improvement was maintained in all groups without deterioration over time
  • Radiological damage was very low, even after 8 years
  • The percentages of patients in clinical remission and in drug-free remission were stabilized

Adapted from Dirven L, et al: Presented at ACR 2011; Poster #2200

best 8 year results of a das steered treatment study
BeSt: 8-Year Results of aDAS-steered Treatment Study

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • This study's powerful message is that if you treat to target (with whatever works for your patient) they will do well
    • Some will even be able to come off pharmacotherapy entirely
  • Despite the push to use biologics early, studies like the BeSt trial demonstrated the cost avoidance of the more expensive therapies does not come at the expense of clinical or radiologic control

Commentary on Dirven L, et al: Presented at ACR 2011; Poster #2200

ra anti tnf therapy and risk of malignant melanoma a nationwide population based study from sweden

RA, Anti-TNF Therapy, and Risk of Malignant Melanoma –a Nationwide Population-Based Study From Sweden

Raaschou P, et al: Presented at ACR 2011;Oral Presentation #2523

ra anti tnf agents and risk of malignant melanoma
RA, Anti-TNF Agents and Risk of Malignant Melanoma
  • Objectives:
    • To investigate the risk of malignant melanoma in patients with RA compared to the general population
    • To investigate whether anti-TNF treatment influences melanoma risk in RA
  • Subjects: 56,336 patients with RA from the national Swedish outpatient registry
    • Included 8,453 patients taking biologics
    • General-population controls were matched for age, sex, and county of residence
  • Methodology:
    • Relative risks for malignant melanoma and all-site cancer were assessed overall and by time since start of anti-TNF therapy

Adapted from Raaschou P, et al: Presented at ACR 2011; Oral Presentation #2523

study population characteristics
Study Population Characteristics

Adapted from Raaschou P, et al: Presented at ACR 2011; Oral Presentation #2523

risk of malignant melanoma in biologic na ve ra vs general population
Risk of Malignant Melanoma inBiologic-naïve RA vs. General Population

80

RR: 1.1

(95% CI: 0.9 – 1.4)

60

54

46

Incidence per 100,000 patient-years

40

20

0

RA

General population

Adapted from Raaschou P, et al: Presented at ACR 2011; Oral Presentation #2523

risk of malignant melanoma in anti tnf patients vs biologic na ve ra
Risk of Malignant Melanoma inAnti-TNF Patients vs. Biologic-naïve RA

80

71

RR: 1.6

(95% CI: 1.1 – 2.4)

60

54

Incidence per 100,000 patient-years

40

20

0

Anti-TNF RA patients

Biologic-naïve RA

Adapted from Raaschou P, et al: Presented at ACR 2011; Oral Presentation #2523

time since treatment start anti tnf exposed vs unexposed in ra
Time Since Treatment Start:Anti-TNF Exposed vs. Unexposed in RA

Adapted from Raaschou P, et al: Presented at ACR 2011; Oral Presentation #2523

ra anti tnf agents and risk of malignant melanoma conclusions
RA, Anti-TNF Agents and Risk of Malignant Melanoma: Conclusions
  • In the absence of anti-TNF therapies, RA patients do not appear to be at elevated risk of malignant melanoma
  • Patients selected for and treated with anti-TNF have a higher risk of malignant melanoma than biologic-naïve RA patients
  • Malignant melanoma is a rare outcome

Adapted from Raaschou P, et al: Presented at ACR 2011; Oral Presentation #2523

ra anti tnf agents and risk of malignant melanoma1
RA, Anti-TNF Agents and Risk of Malignant Melanoma

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • In this study from Sweden, the relative risk for melanoma was increased in RA patients on anti-TNFs
    • The absolute risk, however, was low, and in fact the number needed to treat was more than 1000
  • The overall cancer risk was not increased
  • Is the glass half empty or half full?
    • Most patients should be reassured by these data, but cancer-phobic patients may not be

Commentary on Raaschou P, et al: Presented at ACR 2011; Oral Presentation #2523

galloway jb et al presented at acr 2011 oral presentation 2524

Opportunistic Infections in Patients Exposed to Anti-Tumour NecrosisFactor Therapy:Results From the British Society for Rheumatology Biologics Register

Galloway JB, et al: Presented at ACR 2011;Oral Presentation #2524

anti tnf agents and opportunistic infections bsrbr
Anti-TNF Agents and Opportunistic Infections (BSRBR)
  • Objective: To establish the risk and pattern of opportunistic infections (OI) during treatment with anti-TNF agents in RA
  • Subjects: 11,864 anti-TNF and 3,666 non-biologic DMARD patients from the British Society for Rheumatology Biologics Register (BSRBR)
  • Methodology:
    • The BSRBR drew up a list of OI at its outset
    • For this analysis, infection rates were compared using Cox proportional hazards, adjusted for confounders

Adapted from Galloway JB, et al: Presented at ACR 2011; Oral Presentation #2524

anti tnf agents and opportunistic infections patient characteristics
Anti-TNF Agents and Opportunistic Infections: Patient Characteristics

ETN: etanercept; IFX: infliximab; ADA: adalimumab

Adapted from Galloway JB, et al: Presented at ACR 2011; Oral Presentation #2524

summary of opportunistic infections in ra dmard vs anti tnf
Summary of Opportunistic Infections in RA: DMARD vs. Anti-TNF

Adapted from Galloway JB, et al: Presented at ACR 2011; Oral Presentation #2524

anti tnf agents and risk of opportunistic infections bsrbr
Anti-TNF Agents and Risk of Opportunistic Infections (BSRBR)

8.0

4.0

2.0

Hazard ratio (95% Confidence interval)

1.5

(0.3, 7.8)

2.8(1.0, 7.8)

1.0

0.5

DMARD

Anti-TNF (Unadjusted)

Anti-TNF (Adjusted*)

*Adjusted for age, gender, disease activity, disease duration, disability, COPD, diabetes, baseline steroid use, year of entry into study

Adapted from Galloway JB, et al: Presented at ACR 2011; Oral Presentation #2524

risk of opportunistic infections comparison among anti tnf agents
Risk of Opportunistic Infections: Comparison Among Anti-TNF Agents

*Adjusted for age, gender, disease activity, disease duration, disability, COPD, diabetes, baseline steroid use, year of entry into study

Adapted from Galloway JB, et al: Presented at ACR 2011; Oral Presentation #2524

anti tnf agents and risk of opportunistic infections conclusions
Anti-TNF Agents and Risk of Opportunistic Infections: Conclusions
  • The absolute rate of opportunistic infections (OI) was non-significantly higher in anti-TNF exposed patients
    • The infliximab cohort accounted for 44% of these cases
    • The absolute risk of OI was very low
  • The pattern of risk seen in this analysis has also been reported by other registries
  • This adds weight to the evidence that infliximab may carry a greater risk of OI than other anti-TNF agents

Adapted from Galloway JB, et al: Presented at ACR 2011; Oral Presentation #2524

anti tnf agents and risk of opportunistic infections bsrbr1
Anti-TNF Agents and Risk of Opportunistic Infections (BSRBR)

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • These findings corroborate previous studies and add weight to the evidence that infliximab may carry a greater risk of opportunistic infection than either etanercept or adalimumab

Commentary on Galloway JB, et al: Presented at ACR 2011; Oral Presentation #2524

mercer lk et al presented at acr 2011 oral presentation 2525

The Risk of Solid Cancer in Patients Receiving Anti-Tumour Necrosis Factor Therapy for Rheumatoid Arthritisfor up to 5 Years:Results From the British Society for Rheumatology Biologics Register

Mercer LK, et al: Presented at ACR 2011;Oral Presentation #2525

anti tnf agents and risk of solid cancers bsrbr
Anti-TNF Agents and Risk of Solid Cancers (BSRBR)
  • Objective: To determine whether anti-TNF use influences the risk of cancer when used in routine clinical practice for RA
  • Subjects: 3,543 DMARD patients and 11,719 anti-TNF patients from the British Society for Rheumatology Biologics Register (BSRBR)
    • Patients with history of solid cancer were excluded
  • Methodology:
    • Rates of solid cancer in the anti-TNF and DMARD cohorts were compared using adjusted multivariate Cox proportional hazards models
    • Site specific analyses were also performed for the most common sites: colorectal, lung/bronchus and female breast

Adapted from Mercer LK, et al: Presented at ACR 2011; Oral Presentation #2525

anti tnf agents and risk of solid cancers bsrbr1
Anti-TNF Agents and Risk of Solid Cancers (BSRBR)

1.5

1.2

1.0

Hazard ratio for anti-TNF(95% CI)

0.73

0.94

0.88

0.8

0.6

Unadjusted

Age/gender adjusted

Fully adjusted*

* Adjusted for baseline age, gender, smoking, RA duration, NSAID use, comorbidity and year of registration

Adapted from Mercer LK, et al: Presented at ACR 2011; Oral Presentation #2525

anti tnf agents and risk of solid cancers agent specific analysis bsrbr
Anti-TNF Agents and Risk of Solid Cancers: Agent-specific Analysis (BSRBR)

1.5

1.2

1.0

0.87

Fully adjusted hazard ratio* (95% CI)

0.94

0.88

0.81

0.8

0.6

Infliximab

Anti-TNF

Etanercept

Adalimumab

* Adjusted for baseline age, gender, smoking, RA duration, NSAID use, comorbidity and year of registration

Adapted from Mercer LK, et al: Presented at ACR 2011; Oral Presentation #2525

anti tnf agents and risk of solid cancers analysis by duration of follow up bsrbr
Anti-TNF Agents and Risk of Solid Cancers: Analysis by Duration of Follow-up (BSRBR)

3.0

2.0

1.5

1.2

Fully adjusted hazard ratio for anti-TNF* (95% CI)

1.0

1.18

0.74

0.88

1.00

1.01

0.5

Overall

2nd year

3rd year

4th year

5th year

* Adjusted for baseline age, gender, smoking, RA duration, NSAID use, comorbidity and year of registration

Adapted from Mercer LK, et al: Presented at ACR 2011; Oral Presentation #2525

anti tnf agents and risk of most common solid cancers bsrbr
Anti-TNF Agents and Risk of Most Common Solid Cancers (BSRBR)

3.0

2.0

1.5

1.21

1.2

All Fully adjusted hazard ratio for anti-TNF* (95% CI)

1.0

0.99

0.89

0.88

0.5

Colorectal

All Solid

Lung

Breast

* Adjusted for baseline age, gender, smoking, RA duration, NSAID use, comorbidity and year of registration

Adapted from Mercer LK, et al: Presented at ACR 2011; Oral Presentation #2525

anti tnf agents and risk of solid cancers bsrbr conclusions
Anti-TNF Agents and Risk of Solid Cancers (BSRBR): Conclusions
  • In this UK national cohort of RA patients treated with TNF inhibitors when followed for up to 5 years:
    • No increase in solid cancer risk was seen in patients without prior solid cancer
  • Further follow up is warranted to further assess site-specific risk and allow for longer latency

Adapted from Mercer LK, et al: Presented at ACR 2011; Oral Presentation #2525

anti tnf agents and risk of solid cancers bsrbr2
Anti-TNF Agents and Risk of Solid Cancers (BSRBR)

Commentary from International Literature Search in Rheumatology’s Canadian Editorial Panel

  • The strengths of this study are that:
    • It is a large cohort, linked to a national cancer register
    • It attempted to distinguish risk between the agents
  • It adds to the reassuring data emerging from RCTs and other observational studies (e.g., ARTIS from Sweden) that the risk of solid cancers is not increased in patients receiving any of the anti-TNF agents

Commentary on Mercer LK, et al: Presented at ACR 2011; Oral Presentation #2525