HIGHLIGHTS OF SAN DIEGO

2013 CCO INDEPENDENT CONFERENCE

COVERAGE

of the 2013 ACR/ARHP Annual Meeting*

Faculty
Vivian P. Bykerk, MD, FRCPC
Associate Professor of Medicine
Division of Rheumatology, Department of Medicine
Weill Cornell Medical College
Director, Inflammatory Arthritis Center of Excellence
Rheumatology Attending
Department of Rheumatology, Hospital for Special Surgery
New York, New York
Cong-Qiu Chu, MD, PhD
Assistant Professor of Medicine
Director, OHSU Early Arthritis Clinic
Arthritis and Rheumatic Diseases
Oregon Health & Science University
Portland, Oregon
Disclosures
Vivian P. Bykerk, MD, FRCPC, has disclosed
that she has received consulting fees from
Amgen, Antares, Astellas, Bristol-Myers Squibb,
Crescendo, Genentech, Pfizer, Roche, and UCB;
has received funds for research support from
Boehringer Ingelheim; and that her spouse has
ownership interest in Novartis.
Cong-Qiu Chu, MD, PhD, has disclosed that he
has received consulting fees from
GlaxoSmithKline.
Therapeutics
Bioavailability of Subcutaneous MTX Dosed
by Autoinjector vs Oral MTX in RA
Patients
Randomized, multicenter, 12-wk, open-label, 3-way crossover
phase II study
PK analysis to determine relative bioavailability of
methotrexate (MTX) administered subcutaneously (SC) by an
investigational autoinjector (MTXAI) vs oral MTX
54 pts screened; 50 randomized to different treatment
sequence
Each pt received 1 dose of MTX via each route (SC abdomen,
SC thigh, oral), separated by 1 wk
MTX dosing (10 mg, 15 mg, 20 mg, or 25 mg/wk) determined by
each pts current dose, disease status
Predose and postdose blood sampling
Schiff M, et al. ACR 2013. Abstract 796.
Linear, Dose-Proportionate Increase in
MTX Bioavailability With Autoinjector
Mean MTX area under the
curve consistently higher with
subcutaneous (SC) MTX
autoinjector (MTXAI) vs oral
MTX at all doses
Bioavailability of orally
administered MTX plateaued
at 15 mg
MTX absorption with SC
MTXAI increased in linear,
dose-proportional manner
MTXAI generally safe and
well tolerated
Schiff M, et al. ACR 2013. Abstract 796.
SC MTX autoinjector
(n = 96, thigh + abdomen)
Oral MTX (n = 47)
MTX Dose (mg/wk)
M
e
a
n

A
U
C
0
-
2
4

(
n
g

h
/
m
L
)


3000
2500
2000
1500
1000
500
0
10 15 20 25
Other Outcomes With
Subcutaneous MTX vs Oral MTX
Study examining erythrocyte methotrexate
polyglutamates (MTXPG) for therapeutic
drug monitoring
[1]

At the same dose, switching from oral MTX to
subcutaneous MTX produced higher levels of
erythrocyte MTXPG
Prospective study in juvenile idiopathic
arthritis
[2]
Higher concentrations of erythrocyte MTXPGs
associated with lower than baseline JADAS-27
joint counts at Mo 3 and Yr 1
1. Kaplan R, et al. ACR 2013. Abstract 797. 2. Bulatovic Calasan M, et al. ACR 2013. Abstract 792.
PALACE 2: Apremilast 20 mg vs 30 mg vs
Placebo in Psoriatic Arthritis at Wk 52
Randomized, controlled, phase III trial
Primary endpoint: ACR20 at Wk 16
Apremilast 30 mg BID
(n = 162)

Placebo

(n = 159)

Yr 5
Pts with active
psoriatic arthritis
( 3 swollen,
3 tender joints;
duration 6 mos)
despite previous
DMARD and/or
biologic therapy*
(N = 484)
Cutolo M, et al. ACR/ARHP 2013. Abstract 815.
Wk 16 Wk 52
Apremilast 20 mg BID
(n = 163)
Wk 24
Apremilast 30 mg BID
Apremilast 20 mg BID
*Concurrent use of methotrexate, leflunomide, sulfasalazine permitted (stable doses).

Placebo pts with < 20% decrease in swollen/tender joints from BL to Wk 16 rerandomized to apremilast 20 or 30
mg BID. All other placebo pts rerandomized to apremilast 20 or 30 mg BID at Wk 24.
PALACE 2: Response Rates With
Apremilast Through Wk 52
ACR20 response rates at Wk 16 were higher with apremilast 20 mg (38%; P = .0002)
or apremilast 30 mg (34%; P = .0024) vs placebo (20%) (per protocol)

Endpoints in patients completing 52 wks:
Endpoints at Wk 52* Apremilast 20 mg Apremilast 30 mg
ACR20, % 52.9 52.6
PASI-50,

% 49.2 58.9
PASI-75,

% 27.1 39.3
Mean change in HAQ-DI -0.192 -0.330
Mean change in SF36 Physical Functioning
domain score
4.05 4.97
*Pts who received apremilast from baseline; observed data.

Pts with baseline BSA 3%.

Cutolo M, et al. ACR/ARHP 2013. Abstract 815.
PALACE 2: Apremilast Safety
Outcomes
Diarrhea (5.0%/11.0%/14.8%) and nausea (1.9%/9.2%/16.0%) most
frequently reported AEs through Wk 24 in pts receiving placebo, apremilast
20 mg, and apremilast 30 mg, respectively
Most cases reported during first 2 wks of therapy, generally resolved in 4 wks
even with continued therapy
Severe cases: 3 with apremilast 30 mg through Wk 24; 1 with apremilast 30 mg
and 1 with apremilast 20 mg Wk 24-52
Discontinuation rate in combined apremilast arms: < 2% over 52 wks
Estimated-
Adjusted
Incidence Rate
(/100 Pt-Yrs)*
Placebo-Controlled Period (Wks 0-24) Apremilast Exposure Period (Wks 0-52)
Placebo
(n = 159)
Apremilast
20 mg BID
(n = 163)
Apremilast
30 mg BID
(n = 162)
Apremilast
20 mg BID
(n = 234)
Apremilast
30 mg BID
(n = 234)
1 AE 182.1 278.5 251.4 186.8 191.3
1 SAE 5.5 8.9 6.0 6.3 7.1
D/C for AE 5.4 7.3 17.8 6.7 11.0
Cutolo M, et al. ACR/ARHP 2013. Abstract 815.
*100 x number of pts reporting event divided by pt-yrs up to first event start date.
PALACE 1, 2, 3: Apremilast 20 mg vs
30 mg vs Placebo in Psoriatic Arthritis
Pooled analysis of 3 randomized, controlled phase III trials to assess
efficacy for enthesitis and dactylitis and safety
Apremilast 30 mg BID
(n = 497)
Yr 5
Pts with active
psoriatic arthritis
despite previous
DMARD and/or
biologic therapy*
(N = 1493)
Gladman DD, et al. ACR/ARHP 2013. Abstract 816. 2. Mease PJ, et al. ACR/ARHP 2013. Abstract 310
Wk 16 Wk 52
Apremilast 20 mg BID
(n = 500)
Wk 24
*Concurrent use of methotrexate, leflunomide, sulfasalazine permitted (stable doses).

Placebo pts with < 20% decrease in swollen/tender joints from BL to Wk 16 re-randomized to apremilast 20 or 30
mg BID. All other placebo pts rerandomized to apremilast 20 or 30 mg BID at Wk 24.

Placebo

(n = 496)

Apremilast 30 mg BID
Apremilast 20 mg BID
PALACE 1, 2, 3: Summary of Apremilast Efficacy
in Patients With Psoriatic Arthritis
In all 3 PALACE trials, the ACR20 response rate at Wk 16
was higher with apremilast vs placebo (per protocol)

Apremilast 20 mg: P < .05, PALACE 1 & 3; P < .005, PALACE
2
Apremilast 30 mg: P .0001, PALACE 1 & 3; P <
.005, PALACE 2
Mean changes in MASES (P = .0159) and
dactylitis counts (P = .0121) at Wk 24
significantly greater with apremilast 30 mg
BID vs placebo
1. Gladman DD, et al. ACR/ARHP 2013. Abstract 816.
PALACE 1, 2, 3: Summary of Apremilast
Safety in Patients With Psoriatic
Arthritis
Longer exposure to apremilast generally well tolerated
[1]

Most frequent adverse events in all 3 trials
[2]
:
Diarrhea (14.3%)
Nausea (12.6%)
Headache (10.1%)
Upper respiratory tract infection (10.3%)
Nasopharyngitis (7.4%)
Concerning laboratory abnormalities uncommon, transient
[1,2]
Study investigators concluded that laboratory monitoring not
needed during apremilast treatment
1. Gladman DD, et al. ACR/ARHP 2013. Abstract 816. 2. Mease PJ, et al. ACR/ARHP 2013. Abstract 310.
Intra-articular Sustained Release Triamcinolone (TCA)
vs Standard TCA in Osteoarthritis Patients
12-wk multicenter, randomized,
double-blind, parallel group,
dose-ranging trial in patients with
knee osteoarthritis
10 mg, 40 mg or 60 mg single IA
injection of FX006 (sustained release
TCA) vs IR TCA
Both 10 mg and 40 mg doses of
FX006 resulted in improvement
in pain relief, functional and
responder status vs TCA IR
Safety profile of FX006 comparable
to TCA IR; all doses well tolerated
Bodick N, et al. ACR 2013. Abstract 2668.
Wks Posttreatment
1 2 3 4 5 6 7 8 9 10 11 12
TCA IR 40 mg
FX006 10 mg
FX006 40 mg
L
S

M
e
a
n

C
h
a
n
g
e

F
r
o
m

B
a
s
e
l
i
n
e
,

0
-
1
0

S
c
a
l
e

-2.2
-2.7
-3.2
-3.7
-4.2
-4.7
Weekly Mean of Average Daily
Pain Intensity

*
* *
*P < .1

P < .05

P < .01
*
*





Disease Assessment
Determining Minimally Important Difference in Clinical
Disease Activity Index (CDAI) in Early RA
Observational cohort of patients with ERA used to
determine MID for CDAI improvement
Absolute change > 5 units was best cutpoint to define
MID (AUROC: 0.87)
Different MID cutpoints based on starting disease
activity:
Low disease: MID > 2
Moderate Disease: MID > 6
High Disease: MID > 11
Cutpoints useful for evaluating improvement; increases
usefulness of real-world CDAI measurements
Probability Density Function of
CDAI Change With DAS28-ESR Improvement Stratification
Curtis J, et al. ACR 2013. Abstract 2866.
-80 -60 -40 -20 0 20 40
CDAI Improvement Normal Curves
P
e
r
c
e
n
t

Red bars indicate DAS28ESR improvement (> 1.2 units) in
responders; green bars indicate no DAS28ESR improvement/
worsening (< 0.6 units); brown bars indicate areas of overlap
DAS ESR IMPROVE > 1.2 curve
DAS ESR IMPROVE > 1.2
DAS ESR IMPROVE 1.2 curve
DAS ESR IMPROVE 1.2
25
20
15
10
5
0
Biomarkers for the Diagnosis
of RA
Serum 14-3-3 protein and autoantibodies are
highly specific and discriminated early RA from
controls
[1]
In combination with RF and ACPA, 14-3-3 biomarkers
Identified large proportion of early RA pts
[1]
Established RA pts who are serum 14-3-3
protein negative and 14-3-3 autoantibody
positive are more likely to achieve DAS remission
and good EULAR response with
anti-TNF therapy
[2]
1. Maksymowych W, et al. ACR 2013. Abstract 1786. 2. Maksymowych W, et al. ACR 2013. Abstract 1315.
Biomarkers for RA
Progression
The multibiomarker disease activity (MBDA) blood test assessed
radiographic progression in DMARD-treated pts with established
RA
[1]
Radiographic progression increased nonlinearly with increasing MBDA
Low MBDA score associated with infrequent radiographic progression
High MBDA score associated with increased progression even when DAS28-
CRP or CRP were low
In early RA pts, high MBDA scorealong with elevated
inflammatory biomarkers (CRP, SSA, and IL-6), MMP-1, MMP-3 and
TNF-R1, and VEGFwas associated with radiographic progression at
1 yr
[2]
Early RA pts not responding (DAS28 > 3.2) to MTX after 3 mos had
significantly higher BL CRP (P = .048) and IL-6 (P = .051) values and lower
TNF-R1 (P = .002) and VCAM-1 (P < .001) values vs responders
[2]
1. Li W, et al. ACR 2013. Abstract 1788. 2. Hambardzumyan K, et al. ACR 2013. Abstract 1789.
Angiogenic Factor Dysregulation Predicts
Poor Pregnancy Outcome Risk in SLE
Alterations in balance of angiogenic factors early in pregnancy
predict poor pregnancy outcomes in SLE and/or aPL pts
Dysregulation of placentally derived angiogenic factors (sFlt1,
PlGF, and VEGF) disrupts vascular homeostasis and placental
development
Contributes to placental insufficiency and preeclampsia
Elevated sFlt1 levels early in pregnancy are strongly associated
with subsequent PE and other poor pregnancy outcomes
Ratio of sFLt1/PlGF may be used as early as 16-19 wks
gestation to identify pts at risk of poor pregnancy outcomes

Salmon J et al. ACR 2013. Abstract 765.
Treatment Approaches
OPERA: Methotrexate vs Methotrexate +
Adalimumab in Early Rheumatoid Arthritis
Randomized, double-blind, placebo-controlled phase III 2-yr trial
[1,2]
Endpoints: 1 DAS28CRP < 3.2; 2 remission and improved function rates
Higher remission rates and improved physical function in adalimumab arm at Yr
1
[1]
; current analysis reports Yr 2 data
[2]

Methotrexate 20 mg/wk +
Adalimumab 40 mg Q2W*
(n = 89)
Methotrexate 20 mg/wk
Methotrexate 20 mg/wk

Methotrexate 20 mg/wk + Placebo*
(n = 91)

Yr 2 Yr 1
*In both tx arms: pts with DAS28 3.2 and 1 swollen joint after 12 wks add sulfasalazine 2 g/day + hydroxychloroquine 200 mg/d
after 3 mos; if DAS28 3.2 and 1 swollen joint after 3 mos triple therapy, biologic agent (not adalimumab) added through Wk 52,
then switched to adalimumab 40 mg Q2W; intra-articular triamcinolone administered at clinic visits if any joint swollen.
Pts with early
(duration
< 6 mos)
rheumatoid
arthritis
(N = 180)
1. Hrslev-Petersen K, et al. Ann Rheum Dis. 2013;[Epub ahead of print].
2. Hrslev-Petersen K, et al. ACR/ARHP 2013. Abstract 2687.
OPERA: No Significant Difference in Yr 2
Outcomes Between Treatment Groups
Methotrexate dose and use of intra-articular glucocorticoid, triple
therapy, and biologics similar between treatment arms
Rates of DAS28CRP < 3.2 at Mos 12, 16, 20, and 24 similar between
arms
Hrslev-Petersen K, et al. ACR/ARHP 2013. Abstract 2687.
Outcome, %
Yr 1 Yr 2
DMARD DMARD +
Adalimumab
P
Value
DMARD DMARD +
Adalimumab
P
Value
DAS28CRP < 2.6 49 74 .001 69 66 .79
CDAI 2.8 41 61 .01 55 57 .87
SDAI < 3.3 36 57 .007 54 50 .66
ACR/EULAR
Boolean (28)
30 48 .017 44 45 1.00
HAQ < 0.5 63 75 .09 64 70 .49
TICOPA: Tight Control vs Standard
Care in Early Psoriatic Arthritis
Randomized, controlled, single-blind trial

Primary endpoint: ACR20 at Wk 48
Minimal disease activity assessed every 4 wks
Intensive Management to Achieve Minimal
Disease Activity*
(n = 101)

Standard Care per Treating Physician
(n = 105)

Yr 1
*Minimal disease activity criteria: tender joint count 1; swollen joint count 1; PASI 1 or BSA 3; pt pain
VAS 15; pt global activity VAS 20; HAQ 0.5; tender entheseal points 1.
DMARD-naive pts
with early
(< 24 mos), active
psoriatic arthritis
(N = 206)
Coates LC, et al. ACR/ARHP 2013. Abstract 814.
TICOPA: Treatment Algorithm
Coates LC, et al. ACR/ARHP 2013. Abstract 814.
Intensive Management Group
MTX
Start at 15 mg/wk escalating to 25 mg/wk
at Wk 6
MTX and SSZ
Escalating to 1g BID at Wks 4-8, then to
40 mg/kg/day max
MTX and CyA
Increasing by
1 mg/kg/day
every 4 wks
MTX and LEF
Initially 10 mg/day
increasing to
20 mg/day at
Wk 4
MTX and CyA
Increasing by
1 mg/kg/day
every 4 wks
MTX and LEF
Initially 10 mg/day
increasing to
20 mg/day at
Wk 4
Standard Therapy Group
Standard therapy as per
treating physician
1st-line anti-TNF
therapy for 12 wks
2nd-line anti-TNF
therapy for 12 wks
Continue
Continue
MDA
MDA
MDA MDA
MDA
Not MDA
Not MDA
Not MDA ( 3T/S Jts)
Not MDA
( 3T/S Jts)
Not MDA (< 3T/S Jts)
Not MDA (< 3T/S Jts)
OR
OR
TICOPA: Prescribed Treatment
at Wk 48
Coates LC, et al. ACR/ARHP 2013. Abstract 814.
Leflunomide
Methotrexate
Sulfasalazine
Intensive Management Standard Care
Biologic
Combination DMARD
No treatment
100
90
80
70
60
50
40
30
20
10
0
37.0
22.8
29.3
6.5
7.6
12.0
55.4
14.1
TICOPA: Higher Response Rates With
Intensive Management vs Standard Care
Intensive management to achieve minimal disease criteria
associated with significantly higher ACR20, ACR50, and ACR70 rates
at Wk 48 vs standard care in early psoriatic arthritis patients

Coates LC, et al. ACR/ARHP 2013. Abstract 814.
Patients
(%)
Intensive management
Standard care
ACR20
(n = 172)
ACR50
(n = 170)
ACR70
(n = 172)
100
80
60
40
20
0
62
45
51
25
38
17
P = .02
P = .0004
P =.002
TICOPA: More AEs With Intensive
Management vs Standard Care
No deaths in either treatment arm
Safety Outcome Intensive Management Standard Care
Any AE, n 622 249
Drug-related AEs, n (%) 423 (68.0) 179 (71.8)
Serious AEs, n (%) 25 8
Drug-related serious AEs, n 8 2
Common AEs, n
Nausea
Abnormal liver function test
Upper respiratory tract infection
(common cold)
Gastrointestinal upset
Fatigue

54
37

46
35
33

38
39

14
13
8
Coates LC, et al. ACR/ARHP 2013. Abstract 814.
Rituximab Retreatment in Relapsing
ANCA-Associated Vasculitis
RAVE: randomized, double-blind, noninferiority trial compared
cyclophosphamide followed by azathioprine vs rituximab in ANCA-
associated vasculitis
[1]
Primary endpoint: BVAS/WG = 0 and no prednisone at 6 mos
51% of pts in RAVE trial had relapsing disease at baseline
Rituximab more effective than cyclophosphamide/azathioprine in this
subgroup: 67% vs 42% met primary endpoint (P = .01)
[1]
Pts in RAVE with severe flare between 6-18 mos eligible for open-
label rituximab 375 mg/m
2
once/wk x 4 wks
Severe flare defined as BVAS/WG > 3 or 1 major item*
Current analysis evaluated outcomes for patients (N = 17) treated with
open-label rituximab for severe flare
[2]
1. Stone JH, et al. N Engl J Med. 2010;363:221-232.
2. Miloslavsky E, et al. ACR/ARHP 2013. Abstract 2782.
Rituximab Retreatment for
ANCA-Assocd Vasculitis
Flare: Baseline
Characteristics
Characteristic Pts Treated With Open-Label
Rituximab for Vasculitis Flare
(N = 17)
Originally assigned to rituximab in RAVE trial, n (%) 16 (94)
PR3-ANCA positive, n (%) 14 (82)
GPA, n (%) 15 (88)
Relapsing disease at RAVE trial entry, n (%) 11 (65)
Received cyclophosphamide before RAVE entry, n (%) 9 (53)
Mean time to open-label rituximab, days (range) 367 (225-556)
Mean prednisone dose at time of open-label rituximab
treatment (n = 5), mg (range)
8.5 (2.5-15.0)
Renal flare, n (%) 5 (29)
Diffuse alveolar hemorrhage, n (%) 1 (6)
Detectable B cells at flare, n (%) 15 (94)
Rising ANCA at flare, n (%) 14 (82)
Miloslavsky E, et al. ACR/ARHP 2013. Abstract 2782.
Rituximab Retreatment for
ANCA-Assocd Vasculitis
Flare: Efficacy Outcomes
Outcome Pts Treated With Open-Label
Rituximab for Vasculitis Flare
(N = 17)
Remission,* n (%) 15 (88)
Time to remission, days (range) 57 (27-181)
Complete response,* n (%) 12 (71)
Time to complete response, days (range) 142 (95-256)
Complete remission,* n (%) 8 (47)
Time to complete remission, days (range) 182 (121-256)
Flares within 1 yr after open-label rituximab, n (%) 4 (27)
BVAS/WG at flare (range) 2.5 (2-3)
Time to flare from open-label rituximab, days (range) 244 (78-428)
*Remission: BVAS/WG = 0; complete response: BVAS/WG = 0 and prednisone 10 mg;
complete remission: BVAS/WG = 0 and prednisone = 0.
Miloslavsky E, et al. ACR/ARHP 2013. Abstract 2782.
Rituximab Retreatment for
ANCA-Assocd Vasculitis
Flare: AEs
Safety Outcome Pts Treated With Open-Label
Rituximab for Vasculitis Flare
(N = 17)
AE
Grade 1
Grade 2
Grade 3

65
24
2
AE rate in pts receiving open-label rituximab, per pt-yr
Grade 1
Grade 2
Grade 3

4.5
1.7
0.1
AE rate in all pts, per pt-yr
Grade 1
Grade 2
Grade 3

9.4
2.1
0.5
Miloslavsky E, et al. ACR/ARHP 2013. Abstract 2782.
All AEs graded according to National Cancer Institutes Common Terminology Criteria; grade 1: mild AE;
grade 2: moderate AE; grade 3: severe AE
Drug free
(n = 46)
Drug free
(n = 32)
Drug free
(n = 53)
Placebo injections +
Placebo capsules
(n = 65)
Placebo injections + MTX
(n = 65)
ETN 25 mg QW + MTX
(n = 63)
PRIZE: Drug-Free Maintenance of
Remission in Early RA Patients
3-phase PRIZE study evaluated induction and maintenance of clinical remission in adults
with early moderate to severe RA and evaluated impact of treatment reduction and
withdrawal
Emery P, et al. ACR 2013. Abstract 2689.
Wk 52: Pts achieving DAS28 3.2 at Wk 39
and DAS28 < 2.6 at Wk 52 randomized
Pts with early,
moderate to severe RA
treated with open-label
ETN 50 mg QW +
MTX 10-25 mg QW
Patients who did not achieve LDA at Wks 13, 26, 56, and 64 were given corticosteroid boosts.

Over 2-4 wks.

Wk 117
Wk 91: Pts achieving DAS28 3.2
at Wk 91 assigned to dose-tapering

then
monitoring drug free
PRIZE: Phase II and III
Clinical Outcomes
In phase II (Wks 52-91), DAS28 remission and
ACR/EULAR Boolean remission maintained in
high % of pts receiving ETN25 + MTX vs MTX
alone or placebo
In phase 3 (Wks 92-117) following withdrawal of
randomized treatment, remission rates declined
in all groups; significantly more pts in ETN25 +
MTX group maintained remission vs placebo
P < .05 for DAS28 remission (< 2.6) at Wk 117
P < .001 for ACR/EULAR Boolean remission at Wk 117
No unexpected safety findings
Emery P, et al. ACR 2013. Abstract 2689.
HOPEFUL 2: Biologic-Free Disease
Control in Early RA Patients
Observational study to assess effect of withdrawal of biologic therapy on
disease activity and identify predictors of biologic-free disease control in
pts with early RA
*ADA 40 mg every other wk; MTX 6-8 mg every wk.
Outcome assessments:

DAS28-ESR, HAQ-DI, mTSS;

DAS28-ESR, HAQ-DI.
ADA-continued: MTX + ADA
(n = 106)
ADA-withdrawal: MTX alone
(n = 114)
HOPEFUL 1 HOPEFUL 2
Observational Double blind Open label
Adalimumab
(ADA) + MTX*
ADA + MTX
MTX
Tanaka Y, et al. ACR 2013. Abstract 2769.
Wk 0

Wk 26

Wk 52

Wk 78

Wk 104

Pts with early RA
( 2 yrs) and high
disease activity,
naive for MTX or
leflunomide or not
treated with
> 2 DMARDs
(N = 334)
Assigned at investigators discretion
HOPEFUL 2: Low Disease Activity (LDA)
and Remission Following Biologic
Withdrawal
Pts in biologic withdrawal group had significantly higher mean DAS28-ESR scores
at Wk 104 vs biologic-continued group (3.2 vs 2.7; P = .006)
Tanaka Y, et al. ACR 2013. Abstract 2769.
DAS28-ESR < 3.2 LDA
P = .750
P = .093
P = .021
P
a
t
i
e
n
t
s

(
%
)

0 52 78 104
69.2
71.6
70.3
57.9
72.5
55.8
0 0
0 52 78 104
0 0
DAS28-ESR < 2.6 Remission
ADA continued (n = 91) ADA withdrawal (n = 95)
P = .077
P = .017
37.4
50.5 51.6
33.7
53.8
36.8
100
80
60
40
20
0
100
80
60
40
20
0
Wk Wk
P = .026
HOPEFUL 2: Other Outcomes
No significant difference in HAQ-DI score and
mTSS in biologic-continued and biologic-
withdrawal groups at
Wk 104
Achieving DAS28-ESR remission at Wk 52
was a key predictor of maintaining biologic-
free disease control
Tanaka Y, et al. ACR 2013. Abstract 2769.
TREAT: Predictors of Clinically Inactive
Disease in PJIA Treated With Aggressive,
Early Therapy
Secondary analysis
[1]
of randomized, double-blind, placebo-
controlled TREAT study
[2]
to assess:
Time on therapy to first indication of clinically inactive disease (CID)
Duration of CID
Predictors/sustainability of CID
1. Wallace CA, et al. ACR/ARHP 2013. Abstract 790.
2. Wallace CA, et al. Arthritis Rheum. 2012;64:2012-2021.
Methotrexate + Etanercept +
Prednisolone (tapered to 0 by 17 wks)
(n = 42)
Methotrexate
(n = 43)

Yr 1
Patients aged
2-16 yrs with
active PJIA for
< 12 mos
(N = 85)
Mo 4* Mo 6*
*Pts without ACR Pedi 70 by Mo 4 and pts without CID by Mo 6 switched to open-label methotrexate, etanercept, prednisolone.
CID is defined
[2]
as: 1. No joints having active arthritis, 2. No rash, fever, splenomegaly, serositis, or generalized lymphadenopathy
caused by JIA. 3. No active uveitis. 4. Normal range ESR in laboratory where tested. 5. Physicians global assessment of disease
activity score = 0.

TREAT: Baseline Disease Duration and Month-4
Response Predict Clinically Inactive Disease
68% of all pts in TREAT
reached clinically inactive
disease (CID) during study
Higher % of follow-up days
with CID with
methotrexate, etanercept,
prednisone vs methotrexate
alone
42% vs 24% (P = .048)
Higher % of visits with CID
in pts with vs without ACR
Pedi 70 at 4 mos
(P < .00001)
BL disease duration associated
with proportion of visits with
CID
P = .002
Wallace CA, et al. ACR/ARHP 2013. Abstract 790.
0.5
0.4
0.3
0.2
0.1
P
r
e
d
i
c
t
e
d

P
r
o
b
a
b
i
l
i
t
y

(
9
5
%

C
I
)

100 200 300
Duration of S&S at BL (Days)