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EULAR 2013

1


CZP in AxSpA

2


RAPID-AxSpA: Ongoing 204-week trial in adult patients with active AxSpA according to ASAS criteria, including AS (mNY positive) and nr-AxSpA (mNY negative) populations Double-blind and placebo (PBO)-controlled through week 24, dose-blind through week 48, with an

open-label extension (OLE) through week 158

3

AS, ankylosing spondylitis; ASAS, Assessment of SpondyloArthritis; AxSpA, axial spondyloarthritis; mNY, modified New York; nr-AxSpA, nonradiographic axial spondyloarthritis * 0 to 10 numeric rating scale (NRS; from BASDAI item 2); † ULN, upper limit of normal, ULN=7.9 mg/L; ‡ Within the last 3 months from screening, as defined by ASAS criteria; § Patients who failed to achieve an ASAS20 response at both week 14 and week 16 were randomized at week 16 to receive CZP 200 mg Q2W or CZP 400 mg Q4W following loading dose

Landewé et al. Arthritis Rheum. 2012;64:S336 van der Heijde et al. Arthritis Rheum. 2012;64:S730

CZP 400 mg Q4W

12 Week 0

Active AxSpA patients • BASDAI ≥4 • Back pain ≥4* • CRP > ULN† or

MRI evidence of sacroiliitis‡

Primary clinical endpoint: ASAS20

LD: CZP 400 mg (Wk 0, 2, 4)

CZP 400 mg Q4W

PBO escape§

Wk 16 1:1:1 Randomization

24

CZP 200 mg Q2W

LD for both: CZP 400 mg (Wk 16, 18, 20)

CZP 200 mg Q2W

PBO

16

N=325

Loading dose (LD): CZP 400 mg (Wk 0, 2, 4)

n=111 n=107

n=107 PBO

Double-blind, PBO-controlled

Effects of certolizumab pegol (CZP) on the signs and symptoms of AxSpA at week 24 (RAPID-AxSpA)


15.0 15.8 14.0 8.4 7.0 10.0

51.4 47.7 56.5

30.6 30.8 30.4

52.3 58.9 45.1

29.9 25 35.3

0

100

AxSpA AS nr-AxSpA AxSpA AS nr-AxSpA

Patie

nts

(%)

PBO CZP 200 mg Q2W CZP 400 mg Q4W

Landewé et al. EULAR 2013; Oral OP0106

AS, ankylosing spondylitis; ASAS, Assessment of SpondyloArthritis; AxSpA, axial spondyloarthritis; nr-AxSpA, nonradiographic axial spondyloarthritis * P≤0.001; † P<0.05


4

Primary endpoint: A week 12 ASAS20 response was achieved in significantly more patients receiving CZP 200 mg Q2W and CZP 400 mg Q4W compared with patients receiving placebo (PBO) (57.7% and 63.6% vs 38.3%, respectively; P≤0.004) Significant improvements in ASAS20 were observed as early as week 1 (40.5% and 34.6% in the CZP 200 mg

and 400 mg arms, respectively, vs 14.0% in the PBO arm; P<0.001) and were maintained at week 24

Week 24 response and remission rates (NRI)

n= 107 111 107 57 65 56 50 46 51

ASAS40 ASAS partial remission

* * *

* *

† * *

* * †

†

107 111 107 57 65 56 50 46 51


-1.1 -0.4 -0.1

-3.1 -2.3

-0.5

-6

0

Mea

n Δ

from

bas

elin

e

PBO (n=107)CZP (combined doses, n=218)

Landewé et al. EULAR 2013; Oral OP0106

AS, ankylosing spondylitis; AxSpA, axial spondyloarthritis; BASDAI; Bath Ankylosing Spondylitis Disease Activity Index; BASFI; Bath Ankylosing Spondylitis Functional Index; BASMI; Bath Ankylosing Spondylitis Metrology Index; mNY, modified New York; nr-AxSpA, nonradiographic axial spondyloarthritis; * By ASAS criteria; † CZP 200 mg Q2W or CZP 400 mg Q4W following loading dose

Adverse events (AEs) occurred in 70.4% vs 62.6%, serious AEs in 4.7% vs 4.7%, and serious infections in 1.1% vs 0% of CZP (combined dose) pts vs PBO pts No deaths or malignancies were reported

Authors’ conclusion: Both CZP doses rapidly improved symptoms of AxSpA, with similar improvements observed in AS and nr-AxSpA subpopulations, and with no new observed safety signals


5

AxSpA patients (pts)* showed statistically significant improvements in key secondary endpoints when treated with CZP,† compared with pts who received placebo (PBO) Similar improvements were reported with CZP vs PBO in both AS (mNY positive) and nr-AxSpA (mNY

negative) subpopulations

BASDAI BASFI

Week 24 change from baseline in AxSpA pts (LOCF)

P<0.001 P<0.001

P<0.001

BASMI


-1.3 -1.4 -1.3 -0.9 -0.9 -0.8 -0.5 -0.9 -0.1

-3.3 -2.9 -3.7

-2.6 -2.6 -2.7 -2.4 -2 -2.5

-3.2 -3.5 -2.9 -2.8 -2.5

-3 -2.3 -2.3 -2.3

-5

0AxSpA AS nr-AxSpA AxSpA AS nr-AxSpA AxSpA AS nr-AxSpA


Fatigue (NRS)

Patients treated with CZP also had significant improvements in MOS-SPI, SF-36 PCS and MCS components, and AsQoL compared with patients receiving PBO Similar improvements in PROs were observed in both AS and nr-AxSpA subpopulations Relative to PBO patients, CZP-treated nr-AxSpA patients demonstrated a greater improvement in BASFI and

sleep compared to AS patients, and were more likely to reach population norms for SF-36

Authors’ conclusions: Both CZP dosing schedules rapidly improved all PROs, including pain, fatigue, physical function, and HRQoL of AxSpA, in both AS and nr-AxSpA patients

Effects of certolizumab pegol (CZP) on patient-reported outcomes in AxSpA (RAPID-AxSpA)

6

Sieper et al. EULAR 2013; Poster THU0360

AsQoL, ankylosing spondylitis quality of life; BASFI, Bath Ankylosing Spondylitis Functional Index; LOCF, last observation carried forward; MCS, Mental Component Summary; MOS-SPI, Medical Outcome Study Sleep Problem Index; NRS, numeric rating scale; PCS, Physical Component Summary; SF-36, 36-Item Short-Form Health Survey; *P<0.05 vs PBO

Mea

n Δ

from

ba

selin

e

*

Patient-reported outcomes (PROs) from patients enrolled in the ongoing placebo (PBO)-controlled RAPID-AxSpA trial and open-label extension were evaluated following 24 weeks of CZP treatment

Total back pain (NRS)

Mean change from baseline in PROs at week 24 in AxSpA patients (LOCF)

n= 107 111 107 57 65 56 50 46 51 *

* * *

* * * * * *

*

BASFI

* * * * * *

107 111 107 57 65 56 50 46 51 107 111 107 57 65 56 50 46 51


2.0

5.6

3.0

1.1 2.3

1.1 0.6 2.2 1.9

0.8

5.3

2.3 1.1

2.2 1.0 0.3

1.8 1.8 3.0

5.9

3.8

1.2 2.5

1.3 0.8

2.6 1.9

0

10

AxSpA AS nr-AxSpA

7 Effects of certolizumab pegol (CZP) on productivity

in AxSpA patients (RAPID-AxSpA)

van der Heijde et al. EULAR 2013; Oral OP0107

Patients enrolled in the ongoing, placebo-controlled RAPID-AxSpA trial* and open-label extension were evaluated for work and home productivity † following 24 weeks of treatment with CZP

Authors’ conclusions In the overall AxSpA population, CZP improved workplace productivity in employed patients by

reducing absenteeism, presenteeism, and AxSpA interference with work CZP also improved household productivity and increased participation in social and daily activities Similar improvements were observed in AS and nr-AxSpA populations

AS, ankylosing spondylitis; AxSpA, axial spondyloarthritis; LOCF, last observation carried forward; nr-AxSpA, nonradiographic axial spondyloarthritis * Included mNY positive (AS) and ASAS positive/mNY negative (nr-AxSpA) patients with objective signs of active disease (BASDAI ≥4, Back Pain NRS ≥4, CRP > ULN or MRI evidence of sacroiliitis); † Arthritis-specific Work Productivity Survey (WPS) was administered Q4W; ‡ Employed subjects only; § P≤0.05 vs PBO

Work ‡

Social participation days missed at week 24 (LOCF)

Mea

n da

ys (p

er m

onth

)

Household Social

n = 67 31 36 107 57 50 107 57 50 111 65 46 77 48 29 111 65 46 80 41 39 107 56 51 107 56 51


Work ‡ Household Social Work ‡ Household Social

§

§ § § § §

§ § §

§


CZP in PsA

8


RAPID-PsA: Ongoing 158-week trial in adult patients with active PsA Double-blind and PBO-controlled through week 24, dose-blind through week 48, with an open-label extension

(OLE) through week 158 Enrolled patients included those who experienced secondary failure to 1 previous anti-TNF agent

9

CASPAR, Classification Criteria for Psoriatic Arthritis; DMARD, disease-modifying antirheumatic drug; mTSS, modified total Sharp score; PsA, psoriatic arthritis; SJC, swollen joint count; TJC, tender joint count Mease et al. Arthritis Rheum. 2012;64:S1107

Gladman et al. Arthritis Rheum. 2012;64:S242 van der Heijde et al. EULAR 2013; SAT0281

CZP 400 mg Q4W

12 Week 0

Active PsA patients • PsA ≥6 mo by CASPAR • Skin lesion • >3 TJC/SJC • CRP or ESR > ULN

• Failed ≥1 previous DMARD

Primary clinical endpoint ACR20

LD: CZP 400 mg (Wk 0, 2, 4)

CZP 400 mg Q4W

Placebo escape

Week 16

Randomization 1:1:1

24

CZP 200 mg Q2W

LD for both: CZP 400 mg (Wk 16, 18, 20)

CZP 200 mg Q2W

Placebo

16

N=409

Loading dose (LD): CZP 400 mg (Wk 0, 2, 4)

n=138 n=135

n=136 PBO

Double-blind, placebo-controlled

Effects of certolizumab pegol (CZP) on the signs and symptoms of PsA at Week 24 (RAPID-PsA)

Primary radiographic endpoint Δ mTSS

Authors’ conclusion: Both CZP doses improved symptoms of PsA compared with placebo, with no new observed safety signals


11.5

26.4

61.3 64.5 56.5 56.3

0

100

Prior anti-TNF Anti-TNF naïve

Patie

nts

(%)


13.8 15.5 14.3 14.3 5.2 3.4 3.6

10.7

37.7 49.1

59.5

81.1

17.0

37.7 29.7

59.5 42.9 50.0

52.9

73.5

23.8 26.2 14.7

47.1

0

100

12 24 12 24 12 24 12 24

Patie

nts

(%)

Mease et al. EULAR 2013; Poster SAT0298

*CZP 400 mg at wk 0, 2, and 4 (loading dose) followed by either CZP 200 mg Q2W or CZP 400 mg Q4W SC † P<0.001 vs PBO ‡Statistics not reported for the post hoc analyses

Serious adverse events occurred in 7% of combined CZP-treated patients vs 4% in PBO Authors’ conclusion: Both CZP doses rapidly improved symptoms of PsA compared with placebo,

with no new observed safety signals Patients with higher BL PASI were more likely to achieve a PASI75 and a PASI90 response Similar ACR response rates with CZP were observed in pts with and without prior anti-TNF exposure

Impact of prior anti-TNF therapy and skin lesions on the effectiveness of treating PsA patients with CZP (RAPID-PsA)

10

The efficacy and safety of certolizumab pegol (CZP) was assessed in adult patients with active psoriatic arthritis (PsA) in RAPID-PsA Through week 24, patients (N=409) were randomized to either placebo (PBO) or 1 of 2 CZP doses*

Post hoc analyses of PASI response by baseline (BL) PASI score (NRI)‡

PASI75 PASI90

n= 26 31 23 110 107 112 n= 58 53 42 28 37 34 58 53 42 28 37 34

Week

BL PASI <10 ≥10 <10 ≥10

Week 24 ACR20 response by prior anti-TNF use (NRI)

† †

† †


In post hoc analyses, similar levels of PRO improvement were observed in patients with and without prior anti-TNF exposure

Authors’ conclusions: Both CZP dosing schedules improved multiple PROs in patients with PsA, relative to patients receiving PBO

Effects of certolizumab pegol (CZP) on patient-reported outcomes in active PsA (RAPID-PsA)

11

Gladman et al. EULAR 2013; Poster SAT0260

DLQI, Dermatology Life Quality Index; FAS, Fatigue Assessment Scale; MCS, Mental Component Summary; PCS, Physical Component Summary; PsAQoL, PsA quality of life; SF-36, 36-Item Short-Form Health Survey; VAS, visual analog scale * CZP 400 mg at wk 0, 2, and 4 (loading dose) followed by either CZP 200 mg Q2W or CZP 400 mg Q4W SC † P<0.05 vs PBO

Baseline (BL) and mean change from baseline (CFB) in PROs at week 24 in PsA patients (LOCF)

PRO

PBO (n=136)

CZP 200 mg Q2W

(n=138)

CZP 400 mg Q4W

(n=135) BL Wk 24 CFB BL Wk 24 CFB BL Wk 24 CFB

FAS 5.8 -0.6 6.3 -2.2† 6.2 -1.9† Pain (VAS) 60.0 -11.2 59.7 -28.6† 61.1 -28.4† HAQ DI 1.30 -0.17 1.33 -0.52† 1.29 -0.43† SF-36 (PCS) 33.8 +2.14 33.1 +8.43† 33.2 +7.58† SF-36 (MCS) 42.4 +0.73 40.7 +5.49† 41.9 +3.49† PsAQoL 10.9 -1.27 11.1 -4.43† 11.3 -3.30† DLQI 7.9 -1.4 9.2 -6.3† 8.5 -5.2†

Patient-reported outcomes (PROs) were assessed in adult patients with active psoriatic arthritis (PsA) in the ongoing RAPID-PsA study Through week 24, patients (N=409) were randomized to either placebo (PBO) or 1 of 2 CZP doses*


12 Effects of certolizumab pegol (CZP) on social

participation in PsA patients (RAPID-PsA)

Kavanaugh et al. EULAR 2013; Poster SAT0276

1.6

4.7

2.8

0.2

2.4

1.1 0.6

2.5

1.0

0

5PBOCZP 200 mg Q2WCZP 400 mg Q4W

Work and social days missed in PsA patients treated with CZP for 24 weeks (LOCF)

Days

mis

sed/

mon

th,

mea

n

‡

‡

Patients receiving CZP also had a reduced number days/month in which productivity at work or in the home was reduced by 50% due to arthritis symptoms, compared with patients receiving PBO

Authors’ conclusions CZP significantly improved workplace productivity in employed patients with PsA by reducing

absenteeism and presenteeism, compared with patients receiving PBO PsA patients receiving CZP also experienced improved household productivity and increased

participation in social and leisure activities relative to PBO LOCF, last observation carried forward Arthritis-specific Work Productivity Survey (WPS) was administered Q4W * CZP 400 mg at wk 0, 2, and 4 (loading dose) followed by either CZP 200 mg Q2W or CZP 400 mg Q4W SC; † Employed subjects only; ‡ P≤0.05 vs PBO

Work days missed† Household work days missed

Family/social/lesiure days missed

‡

‡ ‡

n=77 n=83 n=83 n=136 n=135 n=138 n=136 n=135 n=138

Changes in home/work productivity in response to treatment with CZP was evaluated in adult patients with active psoriatic arthritis (PsA) in the ongoing RAPID-PsA study Through week 24, patients (N=409) were randomized to either placebo (PBO) or 1 of 2 CZP doses*


Impact of imputation methodology on reported radiographic progression outcomes in PsA patients (RAPID-PsA)

13

mTSS, modified total Sharp score * CZP 400 mg at wk 0, 2, and 4 (loading dose) followed by either CZP 200 mg Q2W or CZP 400 mg Q4W SC; †P<0.05 vs PBO

van der Heijde et al. EULAR 2013; Poster SAT0281

Imputation in pts with <2 X-rays available

LS mean mTSS CFB at Wk 24 (SE) % of Non-progressors at Wk 24

PBO

(n=136)

CZP 200 mg Q2W

(n=138)

CZP 400 mg Q4W

(n=135)

CZP combined

(n=273)

PBO

(n=136)

CZP 200 mg Q2W

(n=138)

CZP 400 mg Q4W

(n=135)

CZP combined (n=273)

Prespecified imputation methodology 28.92 (7.73) 11.52 (7.59) 25.05 (7.92) 18.28 (6.07) 80.1 93.5† 90.4† 91.9†

No imputation 0.29 (0.08) 0.01 (0.08)† 0.12 (0.08) 0.06 (0.06)† 86.6 96.2† 96.7† 96.5†

Median mTSS CFB of all pts observed 0.28 (0.07) 0.01 (0.07)† 0.11 (0.08) 0.06 (0.06)† 87.5 96.4† 97.0† 96.7†

Mean mTSS CFB of all pts observed 0.28 (0.07) 0.01 (0.07)† 0.11 (0.08) 0.06 (0.06)† 87.5 96.4† 97.0† 96.7†

Maximum mTSS CFB of all pts observed 0.66 (0.13) 0.18 (0.13)† 0.52 (0.13) 0.35 (0.10)† 79.4 92.8† 88.1 90.5†

Maximum mTSS CFB by treatment group 0.39 (0.11) 0.14 (0.11) 0.49 (0.12) 0.31 (0.09) 79.4 92.8† 88.1 90.5†

Radiographic progression was evaluated in patients with active psoriatic arthritis (PsA) enrolled in the 24-week, placebo (PBO)-controlled portion of the ongoing RAPID-PsA study Patients (N=409) were randomized to either placebo (PBO) or 1 of 2 certolizumab pegol (CZP) doses*

The prespecified imputation analysis overestimated radiographic progression in all arms Conventional post hoc analyses suggested that CZP inhibited radiographic progression

compared to PBO Patients with mTSS ≤6 (median score) or CRP ≤15 mg/L at BL showed little radiographic progression in both

the CZP and PBO groups Higher BL mTSS and elevated CRP were also associated with a higher rate of non-progression in CZP vs

PBO groups Authors’ conclusions: Conventional imputation methods showed that CZP inhibited radiographic

progression in PsA patients, particularly in those with a higher risk of progression


CZP in RA

14


PBO + MTX

Safety and efficacy of certolizumab pegol (CZP) + MTX after 5 years of treatment in RA patients (RAPID-OLE)

Keystone et al. EULAR 2013; Abstract THU0192

* CZP 400 mg every 2 weeks is not an approved maintenance dose. For maintenance, the approved dose of CZP is 200 mg every other week, or alternatively, 400 mg every 4 weeks may be considered

RAPID 1 (OLE)

CZP 400 mg Q2W* + MTX for ≥6 months then CZP 200 mg Q2W + MTX

CZP 400 mg Q2W* + MTX

Week 0 52 256 (4.9 years) 334 (6.4 years)

Randomization

CZP 200 mg Q2W + MTX RAPID 1

Patient retention and efficacy data Safety data

Eligible RA patients were enrolled in the open-label extension (OLE) to the RAPID 1 study to assess the safety and efficacy of CZP plus MTX over 5 years in RA

In this OLE to the RAPID 1 study, patients were initially treated with MTX plus CZP 400 mg Q2W,* with the CZP dose decreased to 200 mg Q2W after ≥6 months

15


0

100

0 100 200Week from first dose of CZP

Withdrawal due to AEs or lackof efficacyWithdrawal due to any reason

68.7%

55.3%

78.9%

73.4%

52 256

Patient censored

Ret

entio

n ra

te (%

) K

apla

n-M

eier

est

imat

or

72.6%

61.2%

16

Safety and efficacy of certolizumab pegol (CZP) + MTX after 5 years of treatment in RA patients (RAPID-OLE)

1. Keystone et al. EULAR 2013; Abstract THU0192 2. Keystone et al. EULAR 2013; Poster THU0192

Authors’ conclusions: CZP plus MTX provided a favorable risk-benefit profile over 5 years of treatment in RA patients

Safety data to week 3341 (safety population, N=846)

Patient retention to week 256 (ITT, N=783)2

CZP 400 mg Q2W, reduced to 200 mg Q2W after ≥6 months. Missing categorical data were imputed by nonresponder imputation (NRI) and missing continuous measures were imputed by last observation carried forward (LOCF)

Event rate per 100 pt-years

Any AE 285.6

Urinary tract infection 7.8

Nasopharyngitis 7.4

Upper RT infection 7.3

Any serious AE 18.4

Serious infection 5.4

Serious malignancy 1.0

Incidence rate per 100 pt-years

AEs leading to withdrawal 3.77

AEs leading to death 0.44

Tuberculosis2 0.6

Number of patients

Deaths 16

Malignancies 4

Infections 3

Cardiovascular events 2

CZP completers (n=507) ITT population (n=783)

ACR20/50/70 response rate 74.6%/57.4%/39.6% 59.0%/43.7%/28.8%

DAS28(ESR) remission rate 25.2% 20.3%

Selected efficacy data to week 2561


FcRn binding and FcRn-mediated transcytosis of anti-TNF agents

In vitro quantification of anti-TNF binding affinities for human neonatal Fc receptor (hFcRn) and FcRn-mediated transcytosis

17

Baker et al. EULAR 2013; Poster FRI0162

Authors’ conclusions ADA, IFX, and ETA demonstrated binding affinity to hFcRn, and were actively transported across

an hFcRn-expressing epithelial monolayer CZP and the non-PEGylated CZP Fab’ fragment did not demonstrate detectable binding to hFcRn

Anti-TNF Kd

IFX 132 nM

ADA 225 nM

ETA 1500 nM

CZP ND

Non-PEGylated CZP Fab’ ND

ADA, adalimumab; CZP, certolizumab pegol; ETA, etanercept; Fab; fragment antigen binding; Fc, fragment, crystallizable; Kd, dissociation constant; IFX, infliximab; ND, not detected; PEG, polyethylene glycol * Non-FcRn-binding control antibody

Binding affinity of anti-TNF agents for hFcRn Transcytosis of anti-TNFs across hFcRn-expressing epithelial cells

0

300

P146* CZP ADA IFX ETA

ng/m

L

(Mea

n ±

SD o

ver 4

h)

5.9 ng/mL 3.2 ng/mL 159.5 ng/mL 249.6 ng/mL 81.3 ng/mL Average =


The effect of enforcing TB screening rules in the clinical trials of certolizumab pegol (CZP)

The safety database for clinical trials of CZP in rheumatoid arthritis (RA) patients was reviewed through Nov. 2011 to determine the effect of introducing more stringent tuberculosis (TB) screening protocols (according to WHO guidelines) CZP trials were assessed as 2 groups: trials initiated before the 2007 protocol amendment (early trials) and

trials initiated after the protocol amendment (recent trials)

18

Vencovský et al. EULAR 2013; Abstract THU0204

Of the 44 confirmed TB cases, 11 cases were diagnosed after 2008, when the protocol amendment was enforced

Authors’ conclusions: Following implementation of the WHO recommendations for PPD cutoff, the TB rate in CZP trials was similar to that seen with other anti-TNFs

IR, incidence rate; PPD, purified protein derivation; PY, patient-years; WHO, World Health Organization; * All patients in ongoing trials with a baseline PPD ≥5 mm were treated with INH regardless of duration/exposure to CZP treatment ; † Symptoms/risk factors questionnaire; ‡ Recent CZP trials recruited fewer patients from Eastern and Central Europe compared to earlier trials, which may limit comparison

Patients included if PPD negative according to national guidelines

(PPD positivity: <5 - 20 mm)

PPD cutoff: <5 mm Patients with PPD ≥5 mm treated

with INH + 6-month questionnaire†

All patients in ongoing trials with PPD ≥5 mm treated with isonicotinylhydrazine (INH)

n IR/100 PY

CZP safety database 4049 -

Confirmed TB cases Eastern Europe Central Europe Western Europe North America

44 21 18 3 1

0.47 1.02 0.58 0.23 0.05

TB in early trials‡ 42 0.51

TB in recent trials‡ 2 0.18

2007 Retrospective* protocol amendment (recent trials)

Early trials TB cases in CZP clinical trials


1.7 1

7

1.1

0

8

Baseline (n=42) Week 20/24 (n=32)

Work days lost

Work days with productivity reduced by ≥50% due to arthritis

19 Interim analysis of the effectiveness of CZP in RA patients in a noninterventional study (FasT CAN)

Shaikh et al. EULAR 2013; Abstract AB0288

CDAI, Clinical Disease Activity Index; DAS28, Disease Activity Score including 28-joint count; FAS, full analysis set; HAQ DI, Health Assessment Questionnaire Disability Index; RA, rheumatoid arthritis; WPS-RA, rheumatoid arthritis-specific Work Productivity Survey

Effects of CZP on work productivity

(WPS-RA)

Mea

n da

ys

(per

mon

th)

Average gains in household productivity of 1.5- to 3.1-fold were also reported at wk 20/24 Of all 150 patients, 30.7% reported adverse events (AEs), and 1.3% reported serious AEs, including

serious infections (0.7%). There were no deaths Authors’ conclusions: In daily practice in Canada, CZP-treated RA patients achieved improvements

in DAS28 remission, physical function, and workplace and household productivity

Canadian RA patients (N=150) were enrolled in an open-label, observational, noninterventional study of certolizumab pegol (CZP); interim results to Jan. 2012 are presented here

Baseline Week 12 Week 20/24

DAS28 <2.6, % (n/N) 0 11.6

(11/95) 29.5

(23/78)

DAS28 ≤3.2, % (n/N)

1.8 (2/113)

32.6 (31/95)

47.4 (37/78)

CDAI, mean (SD, n)

33.1 (12.1, 113)

18.1 (12.4, 110)

15.8 (14.1, 90)

DAS28, mean (SD, n)

5.3 (1.1, 113)

4.0 (1.3, 95)

3.6 (1.5, 78)

HAQ DI, mean (SD, n)

1.5 (0.6, 113)

1.1 (0.7, 108)

1.0 (0.8, 90)

Efficacy of CZP in RA patients (FAS, n=113)

© 2013 UCB, Inc. All rights reserved. For unsolicited request only. Takeuchi et al. EULAR 2013; Abstract FRI0201

Immunogenicity of certolizumab pegol and consequences on clinical response in RA patients (HIKARI post hoc)

Post hoc analysis of patients* enrolled in the HIKARI trial and its open-label extension, assessing the relationship between clinical response and development of antibodies (Ab) against certolizumab pegol (CZP)

20

ACR, American College of Rheumatology; RA, rheumatoid arthritis * Received CZP 200 mg Q2W without concomitant MTX in the double-blind portion of HIKARI (n=116)

0

6

1 2 4 6 8 12 24

Early development (n=7)

Late development (n=11)

Week

ACR20/50/70 responses at weeks 24 and 52 Development of anti-CZP Ab

Anti-

CZP

Ab

titer

(U

/mL)

Anti-CZP Ab developed in 15.5% of patients through week 24, in 1 of 2 profiles Ab development peaked between weeks 8-12 (“early development,” n=7) Ab development peaked at/after week 24 (“late development,” n=11)

Authors’ conclusions: These results suggest that early, transient development of anti-CZP Ab was not associated with poor long-term clinical response, whereas later development led to loss of response

64 57

45

64

86

36 47

57

27

45

71

18 26 29

0

34 43

0 0

100ACR20ACR50ACR70

All (n=116)

Early Ab (n=7)

Late Ab (n=11)

ACR

resp

onse

, %

All (n=116)

Early Ab (n=7)

Late Ab (n=11)

Week 24 Week 52

© 2013 UCB, Inc. All rights reserved. For unsolicited request only. Tanaka et al. EULAR 2013; Abstract AB0294

The effect of certolizumab pegol (CZP) on long-term control of RA symptoms in a Japanese cohort (J-RAPID and HIKARI) The efficacy of CZP* in RA patients (pts) was examined over 80 weeks of the J-RAPID and HIKARI

studies and their open-label extensions (OLEs)

21

J-RAPID study (with MTX) (n=63) HIKARI study (without MTX) (n=81)

In J-RAPID and HIKARI DB phases, 75.8% (269/355) of CZP and 62.8% (120/191) of PBO pts reported adverse events; incidence rates in the OLEs were similar to those in the DB phases

Authors’ conclusions: CZP provided long-term clinical, functional, and radiographic benefits regardless of concomitant MTX or other DMARDs in a Japanese RA cohort

0

100

0 80 20 40 60

ACR50 ACR70

ACR20

0

100

0 80 20 40 60

ACR50 ACR70 ACR20

ACR

res

pons

e, %

ACR

res

pons

e, %

J-RAPID (n=63)

HIKARI (n=81)

HIKARI (n=34) monotherapy

HIKARI (n=47) + non-MTX DMARDs

DAS28(ESR) remission, % (week 80) 34.9 37.0 32.4 40.4

mTSS, Δ wk 0-80 0.15 1.39 1.42 1.36

HAQ, Δ wk 0-80 -0.64 -0.62 -0.61 -0.62

Week Week

ACR, American College of Rheumatology; DB, double-blind; HAQ, Health Assessment Questionnaire; mTSS, modified total Sharp score; MTX, methotrexate; RA, rheumatoid arthritis; * CZP 200 mg Q2W or CZP 400 mg Q4W

© 2013 UCB, Inc. All rights reserved. For unsolicited request only. Yamanaka et al. EULAR 2013; Abstract THU0199

Predictability of long-term outcomes in RA patients responding to treatment with certolizumab pegol The ability to predict long-term outcomes of treatment with certolizumab pegol (CZP, 200 mg Q2W)

in RA patients was examined in the context of week 12 response (R) or nonresponse (NR)* in a Japanese cohort (J-RAPID and HIKARI trials)

22

Authors’ conclusions: These analyses suggest that DAS28 response at wk12 predicts long-term clinical and structural outcomes regardless of concomitant medication or BL disease status in Japanese patients treated with CZP

Subgroup

Wk 52 remission† in

wk 12 R

Wk 52 remission

in wk 12 NR

Negative predictive

value OR

(95% CI)

Δ mTSS, mean

in wk 12 R

Δ mTSS, mean

in wk12 NR

J-RAPID (n=82) 41.3% 5.3% 0.947 12.65

(1.59-100.76) 0.29 2.23

HIKARI All (n=116) 34.9% 6.7% 0.933 7.5

(1.67-38.66) 1.23 2.79

HIKARI Non-MTX DMARD (n=62) 39.2% 0% 1.000 Not

calculated 1.37 1.93

HIKARI Monotherapy (n=54) 28.6% 10.5% 0.895 3.40

(0.66-7.50) 1.03 3.34

CI, confidence interval; DAS28, Disease Activity Score including 28-joint count; mTSS, modified total Sharp score; MTX, methotrexate; OR, odds ratio; RA, rheumatoid arthritis; * R, DAS28 change ≥1.2 at week 12; NR, DAS28 change <1.2 at week 12 ; † DAS28 <2.6 at week 52

Predictability of week 52 clinical outcomes based on week 12 response to CZP


Analysis of comorbidities and medical management of RA patients in a French claims database

RA patients were identified from the EGB database (N~380,000), a representative sample of individuals covered by the French Public Sickness Fund, and were compared to a matched control group

23

Fautrel et al. EULAR 2013; Abstract THU0512

The crude RA prevalence rate was 3.47/1000 people The gender ratio was 0.33 (M:F) and mean age was 63.3 ± 14.8 years, with a time since admission to full

coverage for RA of 8.8 ± 7.2 years (<2 years in 23.8% of patients)

Authors’ conclusions Anti-TNF adherence in this cohort is similar to results observed in other registries Observed differences in the comorbidity profile of RA patients should be analyzed further

* Doses received were not specified; † P<0.05; ‡ P<0.01

Patients receiving biologics* (n=214)

Frequencies of comorbidities among RA patients

51.3%

20.1%

12.6%

9.8%

4.2% 0.5% 0.5% Etanercept

Adalimumab

Infliximab

Rituximab

Abatacept

Tocilizumab

Anakinra

Patients (%) Control (n=3888) RA (n=1296)

Patients with comorbidities 1625 (41.8) 511 (39.4)

Alzheimer’s disease 50 (3.1) 7 (1.4)†

Asthma 16 (1.0) 13 (2.5)‡

Hypertension (severe) 259 (15.9) 101 (19.8)†

Ischemic heart disease 98 (6.0) 39 (7.6)

Atherosclerosis 65 (4.0) 15 (2.9)

Heart failure 44 (2.7) 12 (2.3)

Angina pectoris 44 (2.7) 11 (2.2)

Malignancies 144 (8.9) 44 (8.6)

Non-insulin-dependent diabetes mellitus 309 (19.0) 80 (15.7)

Insulin-dependent diabetes mellitus 35 (2.7) 14 (2.7)

Depression 56 (3.4) 25 (4.9)


Cost-effectiveness of certolizumab pegol (CZP) in an outcomes-based risk-sharing scheme in Finland

A risk-sharing scheme (RSS) for CZP was evaluated for treatment response and per-patient value in a Finnish population Cost-effectiveness and per-population budget impacts were assessed over a 5-year horizon

24

Asseburg et al. EULAR 2013; Abstract FRI0184

Over 5 years, introducing the CZP RSS for all new patients provided cost savings per patient of €4,796 together with 0.04 additional QALY

If using an RSS, approximately 4.7% of CZP acquisition costs would be refunded The corresponding budget per patient-year was estimated at €27,310, which could potentially be reduced to

an average of €26,178 if all starting patients received CZP under an RSS

Authors’ conclusions: CZP was shown to be effective and cost effective compared to the current mix of treatments in Finland, with an outcomes-based RSS increasing affordability even further

Estimated ACR response at week 12 Patients, %

CZP 72.4% (95% CI: 64.7% – 80.3%)

Adalimumab 60.2%

Etanercept 52.5%

Golimumab 55.5%

RSS for CZP in RA

Week 12 ACR20 response

Responder Nonresponder

Continue CZP

CZP acquisition costs refunded and alternate

therapy initiated


Epratuzumab

25


BILAG scores and improvements at week 48 were similar regardless of total B-cell counts at the start of the study

Authors’ conclusions: The lack of correlation between B-cell counts and week 48 clinical response suggest the MOA for Emab as B-cell modulation, not depletion

26 Effect of long-term treatment with epratuzumab on

B-cell counts and Ig levels in patients with SLE

26

The effect of long-term epratuzumab (Emab) treatment on B cells, T cells, and immunoglobulin (Ig) levels was evaluated in the open-label extension (OLE) study to EMBLEMTM (SL0008)

BILAG score BILAG improvements B cells at EMBLEMTM OLE screening n Mean (SD) n/N % < Median 96 13.9 (12.7) 24/71 33.8

≥ Median 99 13.2 (12.5) 28/79 35.4 P value 0.712 0.833

BILAG, British Isles Lupus Assessment Group index; SLE, systemic lupus erythematosus 1200 mg Emab infused at weeks 0 and 2 of repeating 12-week cycles through week 112

Strand et al. EULAR 2013; Poster THU0286

Results B-cell counts were moderately reduced, plateauing at approximately 50% below

EMBLEMTM baseline at week 112 Ig levels remained with normal ranges


AxSpA (general)

27


AS-EARLY: 12-Week randomized, double-blind, placebo-controlled study Compared etanercept (ETN) with placebo (PBO) in the treatment of nonradiographic axial

spondyloarthritis (nr-AxSpA) patients with insufficient response to NSAIDs Clinical assessments and MRI of spine and sacroiliac joints* were performed at baseline

and week 12

Efficacy of etanercept in nonradiographic axial spondyloarthritis patients (AS-EARLY)

28

Dougados et al. EULAR 2013; Oral OP0108

ETN 50 mg weekly (+ background NSAID†)

PBO (+ background NSAID†)

Primary endpoint: ASAS40 mITT population

Inclusion criteria • Met ASAS AxSpA criteria • Did not meet mNY criteria • Symptom duration 0.25-5 y • BASDAI ≥4 despite NSAID use • Inadequate response to ≥2

NSAIDs

ASAS, Assessment of Spondyloarthritis; AxSpA, axial spondyloarthritis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; mNY, modified New York; mITT, modified intent-to-treat * Average of 2 independent central readers according to Spondyloarthritis Research Consortium of Canada indices; †Specific NSAID and dosage(s) not specified

Week 0 12

Randomization Stratified by MRI evidence of sacroiliitis and geographic region

N values not specified


P=0.040 P=0.016

P=0.019

P<0.001

P<0.001

-0.5 -1.3

-0.8 -1.2 -0.8 -1.1

-2 -1.4

-2.2

-4 -6

0

Mea

n Δ

from

bas

elin

e (S

E)

PBO + NSAID ETN 50 mg QW + NSAID

15.7

38.0

11.9 4.7

23.9 32.4

50.5

25.7 24.3

43.8

0

100

Patie

nts

(%)

ASAS40 (Primary endpoint)

ASAS 20

ASAS PR

Dougados et al. EULAR 2013; Oral OP0108

AS, ankylosing spondylitis; ASAS, Assessment of Spondyloarthritis; ASDAS, Ankylosing Spondylitis Disease Activity Score; AxSpA, axial spondyloarthritis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; mITT, modified intent-to-treat; mNY, modified New York; PR, partial remission; SIJ, sacroiliac joint; SPARCC, Spondyloarthritis Research Consortium of Canada *Range 0-108; † Range 0-72

Authors’ conclusion In a population of AxSpA patients (ASAS+/mNY-) with inadequate response to NSAIDs, ETN was

more effective than PBO in decreasing clinical and MRI-determined measures of disease activity and function

Efficacy of etanercept in nonradiographic axial spondyloarthritis patients (AS-EARLY)

29

AS-EARLY: 12-Week, placebo-controlled study in patients who met the ASAS criteria for AxSpA, but not the mNY criteria for AS (N values not specified)

Response rate at week 12 (mITT)

ASAS 5/6

BASDAI 50

P=0.006

NS P=0.073

P=0.014 P<0.0001

P=0.003

ASDAS CRP BASDAI BASFI SPARCC*

(spine) SPARCC†

(SIJ)

Week 12 change from baseline (mITT)


ABILITY-1: An ongoing, phase 3, randomized controlled trial (RCT) and open-label extension (OLE) study of adalimumab (ADA) in patients (N=185)* with nonradiographic AxSpA (nr-AxSpA)†

This post hoc analysis examined the safety and efficacy of ADA at week 104 in a subpopulation of MRI- or CRP-positive patients

Post hoc analysis of long-term efficacy and safety of ADA in patients with nr-AxSpA (ABILITY-1)

30

Sieper et al. EULAR 2013; Oral OP0109

ADA 40 mg EOW

PBO

AxSpA, axial spondyloarthritis; EOW, every other week; SPARCC, Spondyloarthritis Research Consortium of Canada * Enrolled patients had an inadequate response, intolerance, or contraindication to NSAIDs; † Diagnostic criteria not specified; ‡ Threshold not specified

Week 0 156

n=69

n=73 12 104

(Up to an additional 144 weeks) OLE RCT

Data used in post hoc analysis (75% available, n=107)

MRI/CRP+ subpopulation Positive MRI at baseline (SPARCC ≥2 for SIJ or spine)

or Elevated CRP‡

Total population (N=185)

n=142

Primary endpoint


In the 356.2 PY of ADA exposure during the study, there were 8 serious infections (2.2/100 PY, including 1 case of disseminated TB), 1 case of lupus-like syndrome, and 2 deaths‡ No malignancies or demyelinating diseases have been reported

Authors’ conclusions Almost half of patients were in remission (ASDAS ID or ASAS PR) at week 104, and the majority of week 104

remitters were also in remission at weeks 52 and 80 Long-term safety data are comparable to other rheumatology indications

Sustained remission (Weeks 52, 80, and 104)

82.0 66.0 69.0

49.0 44.0 35.0 28.0

0

100 ADA 40 mg EOW

ASAS 20

ASAS 40

BASDAI 50

Sieper et al. EULAR 2013; Oral OP0109

ASAS, Assessment of Spondyloarthritis; ASDAS ID, Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS <1.3); ASAS PR, ASAS partial remission; AxSpA, axial spondyloarthritis; BASDAI50, Bath Ankylosing Spondylitis Disease Activity Index 50% improvement; PY, patient-years; SPARCC, Spondyloarthritis Research Consortium of Canada; * nr-AxSpA diagnostic criteria not specified. Enrolled patients had an inadequate response or intolerance/contraindication to NSAIDs; positive MRI (SPARCC score ≥2 for SIJ or spine) or elevated CRP levels (threshold not specified) at baseline; † Data as observed; ‡ Suicide and cardiopulmonary failure due to opiate toxicity

Post hoc analysis of long-term efficacy and safety of ADA in patients with nr-AxSpA (ABILITY-1)

31

Post hoc analysis of the ABILITY-1 open-label extension study evaluating clinical response and sustained remission in the MRI/CRP+ subpopulation*

Clinical responses of the MRI/CRP+ subpopulation (completer analysis†)

ASDAS ID

ASAS PR

Patie

nts

(%)

ASDAS ID

ASAS PR

n=107 n=107 n=107 n=105 n=104 n=101 n=102

Week 104

© 2013 UCB, Inc. All rights reserved. For unsolicited request only. Kneepkens et al. EULAR 2013; Poster FRI0426

The effect of anti-adalimumab antibodies on drug levels and clinical response in ankylosing spondylitis patients

The relationship between antibodies-to-adalimumab (ATA), adalimumab (ADA) concentrations, and clinical response/disease activity in ankylosing spondylitis (AS) patients (N=115) was evaluated in a retrospective cohort study for up to 24 weeks of follow-up

32

ADA levels in AS patients with and without detectable ATA at Week 24

Increased ADA levels were significantly associated with ASDAS reductions (P=0.02; RC=-1.1; 95% CI: -2.0 to -0.2) No significant association with BASDAI responses was observed

Authors’ conclusions: ATA correlate with ADA levels and clinical response, suggesting that therapeutic drug monitoring may be a useful tool in treatment optimization

0 12 24

14

0

Med

ian

ADA

conc

entr

atio

n (m

g/L)

ATA negative ATA positive

Week

CI, confidence interval; RC, absolute risk Disease activity was measured using the AS Disease Activity Score, including CRP (ASDAS); BASDAI response was defined as a 50% improvement or an absolute improvement of 2 points on a BASDAI scale of 0-10; ADA dose(s) not specified

P<0.001


PsA (general)

33


PSUMMIT 11

Patients were DMARD-IR and/or NSAID-IR Patients with previous anti-TNF use were

excluded

PSUMMIT 22

Patients with previous anti-TNF use were eligible

Randomization was stratified by site, weight (≤100 kg, >100 kg), and baseline MTX use

Week

UST 45 mg wk 0, 4, and Q12W (PSUMMIT 1: N=205)1 (PSUMMIT 2: N=103)2

UST 90 mg wk 0, 4, and Q12W (PSUMMIT 1: N=204)1 (PSUMMIT 2: N=105)2

PSUMMIT 1 N=6151

PSUMMIT 2 N=3122

PBO wk 0, 4, and Q12W (PSUMMIT 1: N=206)1 (PSUMMIT 2: N=104)2

1-Year results from the ustekinumab PSUMMIT 1 and 2 trials

1. Kavanaugh et al. EULAR 2013; Poster SAT0271 2. Ritchlin et al. EULAR 2013; Oral OP0001

* Blinded early escape: Patients with <5% improvement in both TJC and SJC1,2

*

*

UST 90 mg wk 24, 28, and 40

UST 45 mg wk 24, 28, and 40

0 16 24 52

The long-term safety and efficacy of ustekinumab (UST, anti-IL-12/23) in patients with active psoriatic arthritis (PsA) was assessed in the 52-week extensions of two phase 3 studies: PSUMMIT 11 and 22

Primary endpoint2 ACR20 at Week 24

34


60.3 74.6 68.1

0

100

47.6 60.6

0

100

59.3 38.9

0

100

ACR20 DAS28-CRP PASI75

ACR20, 20% improvement in American College of Rheumatology criteria; DAS28; Disease Activity Score including 28-joint count; PASI75, 75% reduction in Psoriasis Area and Severity Index Adult patients were randomized to receive UST 45 mg or 90 mg at wk 0, wk 4, and Q12W

UST was generally well tolerated, with no deaths or tuberculosis and similar rates of adverse events reported across doses in both studies

Authors’ conclusions Both UST doses yielded improvements in PsA signs/symptoms with favorable and comparable

safety profiles UST was effective in both anti-TNF-naïve and anti-TNF-experienced patients, with greater efficacy in

anti-TNF-naïve patients

Efficacy of ustekinumab after 1 year of treatment in patients with active PsA (PSUMMIT 1/2)

35

The long-term safety and efficacy of ustekinumab (UST, anti-IL-12/23) was assessed in the 52-week extensions of two phase 3 studies: PSUMMIT 11 and 22

Response to UST 90 mg at week 52 in PSUMMIT 1 (n=204)1

Patie

nts

(%)

ACR20 PASI75

Patie

nts

(%)

Anti-TNF naive

Anti-TNF experienced

Response to UST (combined dose) at week 52 in PSUMMIT 2 (n=189)2

ACR

20 (%

) 1. Kavanaugh et al. EULAR 2013; Poster SAT0271

2. Ritchlin et al. EULAR 2013; Oral OP0001


Results from the apremilast PALACE 1 and PALACE 3 studies

Patients with active psoriatic arthritis (PsA) despite prior DMARD and/or biologic use were treated with the oral phosphodiesterase 4 inhibitor apremilast (APR) or placebo (PBO)1,2

In PALACE 3, patients had at least one ≥2-cm psoriatic lesion at baseline2 Randomization was stratified by baseline DMARD use; stable concurrent DMARD therapy was allowed (MTX,

sulfasalazine, leflunomide, or combination)2

1. Kavanaugh et al. EULAR 2013; Oral LB0001 2. Birbara et al. EULAR 2013; Oral OP0104

* Early escape: Patients with <20% reduction in both tender/swollen joint counts re-randomized to APR 30 or 20 mg if first randomized to PBO or remained on the initial APR dose1,2

† PALACE 1: Re-randomization of all remaining PBO patients1

APR 30 mg BID (PALACE 1: N=1681) (PALACE 3: N=1592)

APR 20 mg BID (PALACE 1: N=1681) (PALACE 3: N=1632)

PBO (PALACE 1: N=1681) (PALACE 3: N=1642) 0 16 24

* Week

PALACE 1 N=5041

52 †

PALACE 1: + (N=54)1

PALACE 1: + (N=53)1

PALACE 1: + (N=23)1

PALACE 1: + (N=24)1

PALACE 3 N=505

Per protocol population

N=4862

Primary endpoint2 ACR20 at Week 16

36


63.0

24.8 15.4

54.6

24.6 13.8

0

100

APR20 (n=168)APR30 (n=168)

Kavanaugh et al. EULAR 2013; Oral LB0001

ACR20/50/70, 20%/50%/70% improvement in American College of Rheumatology criteria; APR20, APR 20 mg BID; APR30, APR 30 mg BID; BID, twice a day

Exposure-adjusted incidence rates for adverse events (AEs), severe AEs, and serious AEs were

comparable for weeks 0-24 and 25-52 No safety signals with respect to major cardiac events, malignancies, and opportunistic infections were

observed No cases of lymphoma, tuberculosis, or tuberculosis reactivations were reported

Author’s conclusion: Patients receiving APR for up to 52 weeks continued to demonstrate

meaningful clinical responses with an acceptable AE profile

52-Week safety and efficacy of apremilast in patients with PsA (PALACE 1)

37

Patients (N=504) were treated with apremilast (APR) in the 52-week extension study to PALACE 1 At week 16, significantly more APR20 (31.3%; P=0.0140) and APR30 patients (40.0%; P<0.0001) achieved an

ACR20 (primary endpoint) vs placebo (PBO) patients (19.4%) Following the 24-week PBO-controlled trial, patients were randomized to APR20 or APR30 through week 52

Patie

nts

(%)

ACR20

52-Week response rate of PsA patients treated with APR in PALACE 1

ACR50 ACR70


18.9 NA

26.0 12.0 12.0

29.4 40.0 36.0

23.0 22.0 42.8 42.0 46.0

27.0 21.0

0

100 PBO APR20 APR30

P<0.05

DAS28 <2.6

Birbara et al. EULAR 2013; Oral OP0104

ACR20, 20% improvement in American College of Rheumatology criteria; BID, twice a day; DAS28; Disease Activity Score including 28-joint count; DMARD, disease-modifying antirheumatic drug; PASI50/75, 50%/75% reduction in Psoriasis Area and Severity Index * Actual response rate includes all early escape patients who continued on originally randomized treatment; statistics not performed

Comparable results were seen with APR monotherapy and in combination with DMARD(s) APR was generally well tolerated; serious AEs occurred in 9 PBO, 3 APR20, and 6 APR30 patients

Author’s conclusion: Patients receiving APR experienced significantly improved signs and symptoms of PsA and associated psoriasis compared with PBO, with no new safety signals

Safety and efficacy of apremilast in patients with PsA and current skin involvement (PALACE 3)

38

Patients (per protocol, N=486) with active psoriatic arthritis (PsA) and skin lesions were treated with apremilast (APR) in the placebo (PBO)-controlled PALACE 3 study for 24 weeks Patients were randomized to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30), and stable DMARD

therapy was allowed

PASI50

Patie

nts

(%)

ACR20 Primary endpoint

PASI75

Week 16

Response rate of PsA patients treated with APR in PALACE 3

Week 24

P<0.0001

P<0.05 P<0.05

n=

P<0.05 NS

NS

ACR20* 164 163 159 163 159 164 163 159 84 87 83 84 87 83

P<0.05


RA (general)

39


Serum levels of ADA were inversely correlated with DAS28(ESR) scores (-0.46; 95% CI: -0.66 to -0.21)

Serum ADA levels needed to maintain clinical remission (DAS28 ≤2.6) or low clinical activity (DAS28 2.7-3.2) were estimated based on ROC curves Remission: 3.01 mg/L (AUC, 65.77%; sensitivity, 50%; specificity, 77.77%) Low clinical activity: 3.48 mg/L (AUC, 83.18%; sensitivity, 83.33%; specificity, 77.80%)

Authors’ conclusions There is a negative correlation between the serum level of ADA and DAS28 Serum level of ADA >7.3 mg/L does not increase DAS28 improvements, suggesting dose

modulation may be considered in these patients

40 Correlation between serum adalimumab levels and

clinical response in RA patients

40

Serum levels of adalimumab (ADA) and antibodies to ADA (ATA) were correlated with DAS28(ESR) scores in RA patients (N=56) who had been treated with ADA (doses unspecified) for >6 months

ADA serum level tertiles

Group 1 (n=22) <2.8 mg/L

Group 2 (n=13)

2.8-7.3 mg/L

Group 3 (n=21) >7.3 mg/L

ADA serum level, mg/L 1.56 ± 1.18 4.64 ± 1.15* 12.24 ± 4.45*,†

ATA detected 4 (18%) 0 0

DAS28(ESR) 3.81 ± 1.33 2.64 ± 0.92* 2.53 ± 0.68*

AUC, area under the curve; DAS28, Disease Activity Score including 28-joint count; ESR, erythrocyte sedimentation rate; ROC, receiver operating characteristics

Rosas et al. EULAR 2013; Poster THU0206

Relationship among ADA, ATA and DAS28(ESR), according to ADA tertiles

* Statistically significant vs Group 1; † statistically significant vs Group 2


Comparison of the effects of ABA and ADA on remission and low-disease activity in patients with RA (AMPLE)

Key endpoints Primary endpoint: Non-inferiority of ACR20 response at 1 year Remission (DAS28[CRP] <2.6, CDAI ≤2.8, SDAI ≤3.3, RAPID3 <3, Boolean score ≤1) LDA (DAS28[CRP] ≤3.2, CDAI ≤10, SDAI ≤11, RAPID3 ≤6)

Fleischmann et al. EULAR 2013; Poster SAT0132

125 mg abatacept SC weekly (n=318)

40 mg adalimumab SC biweekly (n=328)

1 Year

Concomitant MTX

n=274 86.2%

n=269 82.0%

Biologic-naïve patients with RA (≤5 years) with inadequate response to MTX

AMPLE is a phase 3b, randomized, investigator-blinded 2-year study on efficacy of abatacept (ABA) and adalimumab (ADA)

41


43.3

59.3

27.9

44.8

23.5

61.0

23.3

62.2

13.5

41.9

61.4

25.5

42.9

24

61.8

24.8

63.5

15.7

0

100 ABA 125 mg QWADA 40 mg QOW

DAS28(CRP)

Fleischmann et al. EULAR 2013; Poster SAT0132

CDAI, Clinical Disease Activity Index; DAS28, Disease Activity Score including 28-joint count; HAQ DI, Health Assessment Questionnaire Disability Index; mTSS, modified total Sharp score; SDAI, Simplified Disease Activity Index; * DAS28(CRP) <2.6, CDAI ≤2.8, SDAI ≤3.3, RAPID3 <3, Boolean score ≤1; † DAS28(CRP) ≤3.2, CDAI ≤10, SDAI ≤11, RAPID3 ≤6

Physical function and radiographic progression after 1 year were analyzed in early responders (remission or LDA at days 85 and 169) >60% of early responders were HAQ DI responders after 1 year (improvement ≥0.3U) >80% of early responders were radiographic nonprogressors after 1 year (∆mTSS ≤2.8)

Authors’ conclusion: Through 1 year, patients treated with ABA or ADA in the AMPLE trial achieved comparable rates of remission and LDA Similar improvements in physical function and radiographic outcomes were also observed

42

AMPLE: Biologic-naïve RA patients with inadequate response to MTX were randomized to receive SC abatacept (ABA; N=318) or adalimumab (ADA; N=328) in combination with stable MTX

Patients meeting remission (REM)* or low disease activity (LDA)† criteria after 1 year

Patie

nts

(%)

Comparison of the effects of ABA and ADA on remission and low-disease activity in patients with RA (AMPLE)

REM LDA REM LDA REM LDA REM LDA REM

RAPID3 CDAI SDAI Boolean


Safety and efficacy of tocilizumab monotherapy and in combination with MTX in early RA

Burmester et al. EULAR 2013; Oral OP0041

MTX*

MTX-naïve, early RA patients (≤2 years) • DAS28 >3.2 • Elevated ESR or CRP • Either ˃1 erosion,

RF+, or anti-CCP+ • N=1157

Week 104

TCZ 8 mg/kg (TCZ8) Q4W + MTX* (primary intervention)

TCZ8 Q4W monotherapy

TCZ 4 mg/kg (TCZ4) Q4W + MTX*

Week 24 Primary endpoint: Proportion of patients achieving DAS28

remission (DAS28[ESR] <2.6)

The clinical, radiographic, and safety profile of tocilizumab (TCZ) ± MTX vs MTX was evaluated in a randomized, blinded trial of MTX-naïve, early RA patients (≤2 years)

43

*Patients who received MTX started at 7.5 mg QW, escalating to 20 mg QW by wk 8


Safety and efficacy of tocilizumab monotherapy and in combination with MTX in early RA

Patients (ITT, N=1157) with early RA (≤2 years) were randomized to receive IV tocilizumab (TCZ) Q4W at 4 mg/kg (TCZ4) + MTX, 8 mg/kg (TCZ8) + MTX, TCZ8 monotherapy, or MTX alone for 104 weeks MTX doses started at 7.5 mg QW, escalating to 20 mg QW by wk 8

Results Primary endpoint: Significantly more patients receiving TCZ8 + MTX achieved DAS28 remission*

at weeks 24 and 52 compared with those receiving MTX alone (P<0.05) Statistically significant improvements in ACR20/50/70, mean mTSS, and HAQ DI were also

observed at wk 52 in the TCZ8 + MTX group compared to MTX alone

Safety Incidences of adverse events (AEs) and serious AEs were similar across treatment groups, while

serious infections were highest in patients on combination therapy 9 deaths were observed across all treatment groups

Authors’ conclusions TCZ treatment resulted in improvements in signs/symptoms of RA, physical function, and in

inhibition of structural joint damage in all treatment groups compared to MTX alone, with consistently greatest improvement in the TCZ8 + MTX group

44

Burmester et al. EULAR 2013; Oral OP0041

HAQ DI, Health Assessment Questionnaire Disability Index; mTSS, modified total Sharp score * DAS28(ESR) <2.6


Effects of continuing etanercept therapy in RA patients with stable low disease activity

van Vollenhoven et al. EULAR 2013; Poster FRI0185

106 Patients screened

91 Patients enrolled

No change to existing

therapy

2 months

73 Patients

randomized

Monitoring to ensure stable LDA/REM

ETN 50 mg/wk + MTX

ETN 25 mg/wk + MTX

PBO + MTX

Week 48

Randomized trial to evaluate whether low disease activity or remission (LDA/REM)* can be maintained in patients taking etanercept (ETN) + MTX if ETN dose is reduced or discontinued

Key inclusion criteria RA patient on ETN 50 mg/wk plus MTX Documented low disease activity or remission (DAS28 ≤3.2) for ≥11 months Stable MTX (dose 7.5-25 mg/wk) No prior biologics except anti-TNF, and no prior attempt to discontinue ETN due to stable disease

Primary outcome % of non-failures† at Week 48

* DAS28 ≤3.2 † Failure was defined as DAS28 >3.2 and an increase in DAS28 ≥0.6; non-failures maintained LDA/REM (DAS28 ≤3.2)

45


A greater likelihood of treatment failure was associated with the following baseline predictors (P<0.10): higher erosion scores, higher VAS pain score, and shorter duration of ETN treatment prior to screening

Adverse events were similar between groups Authors’ conclusions: For RA patients in stable LDA/REM on ETN + MTX, continued treatment

with ETN at 50 mg/wk or 25 mg/wk provides a significantly higher likelihood of maintaining stable disease state over 48 wks than MTX monotherapy These data suggest that an “induction-maintenance” strategy may be feasible in some individual patients,

even in established RA

46 Effects of continuing etanercept therapy in RA

patients with stable low disease activity

46

RA patients (N=73) in stable LDA/REM* on etanercept (ETN) 50 mg/wk + MTX† were randomized to 50 mg/wk ETN, 25 mg/wk ETN, or placebo (PBO) in addition to maintaining MTX

Treatment failure was defined as a DAS28 >3.2 and an increase in DAS28 ≥0.6, or disease progression as determined by investigator or patient; non-failures maintained LDA/REM

ETN 25 mg ETN 50 mg PBO

Non-failures (maintained LDA/REM) 44%

(OR=4.2; CI: 1.0-17.0) P=0.044 vs PBO

52% (OR=4.2; CI 1.7-29.8)

P=0.007 vs PBO 13%

Median time to failure (from randomization) 36 weeks 48 weeks 6 weeks

CI, confidence interval; DAS28, Disease Activity Score including 28-joint count; LDA/REM, low disease activity/remission; OR, odds ratio; VAS, visual analog scale * LDA/REM defined as DAS28 ≤3.2, included patients maintained LDA/REM for for ≥11 months; † Stable dose 7.5-25 mg/wk

van Vollenhoven et al. EULAR 2013; Poster FRI0185

Clinical response at week 48

© 2013 UCB, Inc. All rights reserved. For unsolicited request only. Keystone et al. EULAR 2013; Poster FRI0161

Effect of withdrawing MTX in RA patients with moderate to severe RA (CAMEO)

This prespecified post hoc analysis of the CAMEO trial assessed month 12 responses in patients with moderate disease activity (MDA, DAS28 3.2-5.1) or severe disease activity (SDA, DAS28 >5.1) at baseline

Patients received ETN 50 mg/week + MTX for 6 months, then were randomized to either continue or discontinue MTX

47

More patients in MDA reached LDA at month 6 compared to patients in SDA (61.3% [49/80] vs 35.8% [43/120]; OR=2.5, 95% CI: 1.38-4.41)

Authors’ conclusions: It may be possible to withdraw MTX in a relatively high proportion of patients, but those with initial SDA may need to continue combination therapy

DAS28, Disease Activity Score including 28-joint count; MTX, methotrexate

7

LDA (DAS28 <3.2)

6.08 6.14

4.45

4.34 3.85

3.86

2.91 2.81

4.31

3.39

3.06 3.10

0 6 12

Mea

n D

AS28

(9

5% c

onfid

ence

inte

rval

)

Post hoc analysis of DAS28 in patients with MDA/SDA (N=205)

ETN + MTX (n=41) ETN (n=43) MDA

ETN + MTX (n=66) ETN (n=55) SDA

Month

Randomization

2


Multiple Disease States

48


TB risk in patients treated with TNF antagonists across multiple therapeutic areas

Risk of tuberculosis (TB) with anti-TNF treatment* (± MTX) was evaluated in a meta-analysis of published randomized controlled trials (RCTs) RCTs considered: 45 rheumatic disease (RA, AS, PsA, n=11,638); 26 IBD (n=6352); 15 psoriasis (n=4081)

49

Bruzzese et al. EULAR 2013; Oral OP0070

Authors’ conclusions Anti-TNF treatment significantly increases risk of TB infection The risk seems to be particularly elevated in patients treated for rheumatic disease when

combination therapy with MTX is used AS, ankylosing spondylitis; IBD, inflammatory bowel disease; MTX, methotrexate (dose not reported); OR, odds ratio; PsA, psoriatic arthritis; RA, rheumatoid arthritis; * Infliximab, adalimumab, or certolizumab pegol (doses not reported); † Vs controls

0

34

0

50

Controls (n=7593)

Anti-TNF (n=14,478)

TB c

ases

TB incidence by treatment and therapeutic area

P<0.001

Rheumatic diseases Psoriasis IBD

5 P=0.023†

29 P<0.001†

Anti-TNF monotherapy Anti-TNF + MTX

Patients, N 8808 5644

TB cases, n 8 (OR: 9.9 [0.5-172.4]) 26 (OR: 48.3 [2.9-793.7])


International consensus on treatment targets for spondyloarthritis, including AS and PsA (1 of 3)

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Smolen et al. EULAR 2013; Oral OP0110 AS, ankylosing spondylitis; PsA, psoriatic arthritis

Based on the results of a systemic literature review and expert opinion, an international group of physicians and patients suggested treatment targets for spondyloarthritis (SpA) and recommendations for a treat-to-target management strategy

The task force developed 5 overarching principles and 11 recommendations

Overarching principles

A The treatment target must be based on a shared decision between patient and rheumatologist

B Management of musculoskeletal (MSK) and extra-articular manifestations should be coordinated between the rheumatologist and other specialists

C The primary goal of treating the patient with SpA and/or PsA is to maximize long-term health-related quality of life and social participation through control of signs and symptoms, prevention of structural damage, normalization or preservation of function, avoidance of toxicities, and minimization of comorbidities

D Abrogation of inflammation is presumably important to achieve these goals

E Treatment-to-target by measuring disease activity and adjusting therapy accordingly contributes to the optimization of short-term and/or long-term outcomes



51

Smolen et al. EULAR 2013; Oral OP0110 AS, ankylosing spondylitis; MSK, musculoskeletal; PsA, psoriatic arthritis; SpA, spondyloarthritis

Recommendations: Common Items for SpA

1 Major target: Remission/inactive disease of MSK involvement (and considering extra-articular manifestations)

2 Target should be individualized

3 Clinical remission/inactive disease defined as absence of clinical and lab evidence of inflammatory disease activity

4 LDA/MDA suitable alternative

5 Disease activity measured on signs and symptoms and acute-phase reactants

6 Choice of measure of activity and target may be influenced by other factors

7 Target should be maintained

8 Patient should be appropriately informed

9 Other factors apart from disease activity should be considered



52

Smolen et al. EULAR 2013 ORAL OP0110 AS, ankylosing spondylitis; AxSpA, axial spondyloarthritis; PsA, psoriatic arthritis; SpA, spondyloarthritis

Author’s conclusions: Recommendations may inform patients, rheumatologists, dermatologists, and other stakeholders about expert opinion on reaching optimal outcomes in spondyloarthritis

Recommendations: Specific for individual SpAs

AxSp

A

Quantified measures of disease activity, which reflect the individual peripheral musculoskeletal (MSK) manifestations (arthritis, dactylitis, enthesitis), should be performed and documented regularly in routine clinical practice to guide treatment decisions; the frequency of the measurements depends on the level of disease activity

Factors such as axial inflammation, MRI, etc may also be considered

Perip

hera

l SpA

Measures of disease activity that reflect individual peripheral manifestations should be performed and documented regularly to guide decisions

Other factors may also be considered

PsA Measures of MSK disease activity should be performed regularly to guide decisions

Other factors may also be considered

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