Celltrion Healthcare 102 weeks with Remsima(HCP)

1. BACKGROUND
Biological drugs such as infliximab, a human–mu-
rine chimeric monoclonal antibody targeting tumour
necrosis factor alpha, have greatly improved the man-
agement of debilitating autoimmune diseases such as
rheumatoid arthritis and ankylosing spondylitis, im-
proving patients’symptoms and quality of life. Howev-
er, the high costs of biologics have limited treatment
access in some countries, meaning many patients
who could benefit from this therapy unfortunately do
not receive it. As a consequence, ‘biosimilar’ agents
have been developed to address this unmet need.
These biotherapeutic drugs, which must meet strict
criteria defined by regulatory authorities, are highly
similar to the reference biologic(s) in terms of physic-
ochemical and biological properties, and equivalence
in pharmacokinetics, efficacy and safety must also be
established in clinical trials.
Remsima® (CT-P13; also known as Inflectra® and
infliximab-dyyb) is a biosimilar infliximab. Both
Remsima® and Remicade® share the same mecha-
nism of action and are administered by intravenous
infusion. Remsima® was compared with reference
infliximab in two double-blind studies in patients
with active rheumatoid arthritis (PLANETRA) and in
patients with active ankylosing spondylitis (PLANE-
TAS). In these studies, patients were randomized 1:1
to Remsima® or reference infliximab (both treatments
were given at a dose of 3 mg/kg or 5 mg/kg for pa-
tients with rheumatoid arthritis and ankylosing spon-
dylitis, respectively) at weeks 0, 2, 6 and every 8 weeks
thereafter for up to 54 weeks.1,2
These trials demonstrated that the efficacy, safety
and pharmacokinetics of Remsima® and reference
‘BIOSIMILAR’ DRUGS PROVIDE CONSIDERABLE
COST SAVINGS, BUT HOW EFFECTIVE ARE
THEY FOR LONG-TERM TREATMENT OF PATIENTS
WITH AUTOIMMUNE DISEASES?
NEW DATA FROM THE ‘PLANETAS’ AND ‘PLANETRA’ CLINICAL TRIALS
Scan this QR code
to access
the PLANETRA
extension study.
weeks with
A clear reflection
of innovation, accessibility,
and efficacy
A clear reflection of what has been added to the treatment paradigm.
Evidence based switching,
Evidence supports biosimilar infliximab, Remsima.
Scan this QR code
to access
the PLANETAS
extension study.
Safety is a key consideration when evaluating
long-term therapies, and importantly in both PLANE-
TRA and PLANETAS, Remsima® was well tolerated for
up to 2 years of treatment and there were no nota-
ble differences in safety parameters observed in the
maintenance and switch groups in either extension
study. 3,4
Furthermore, the side effects observed with
Remsima® over long-term treatment were consistent
with the known safety profile of reference infliximab.
In summary, taken together the recently published
102-weekdatafromPLANETASandPLANETRAdemon-
strated that the biosimilar, Remsima® has comparable
efficacy and safety to reference infliximab. Remsima®
remained effective in patients with rheumatoid ar-
thritis and ankylosing spondylitis who received long
term treatment for 2 years, and was equally as effec-
tive and safe in patients who switched from reference
infliximab to Remsima®. Given that Remsima® and
other biosimilars are anticipated to be less expensive
than their biologic counterparts, these drugs are ex-
pected to provide a welcome increase in the number
of patients who can benefit from effective therapy for
debilitating autoimmune diseases.
Figure 4. ACR20 (PLANETRA) and ASAS20 (PLANETAS) response rates were maintained with Remsima®, regardless of anti-drug anti-
body (ADA) status.3,4
PLANETRA ACR20 response rate PLANETAS ASAS20 response rate
Maintenance SwitchMaintenance Switch
Week 54 Week 54Week 102
p=0.85
p=1.00
p=0.35
p=0.68
ADA-
85.7 84.7
ADA+
68.0 70.6
Week 102
p=1.00
p=0.75
ADA-
83.9 84.6
ADA+
70.0
62.5
p=1.00
p=1.00
ADA-
82.2 82.8
ADA+
73.4 73.4
ADA-
75.7 79.0
ADA+
50.0
66.7
ACR20responders,%
100
20
40
60
80
0
ASAS20responders,%
100
20
40
60
80
0
weeks with
1. Yoo DH, Racewicz A, Brzezicki A, et al. A phase III randomized study to
evaluate the efficacy and safety of CT-P13 compared with reference
infliximab in patients with active rheumatoid arthritis: 54-week results
from the PLANETRA study. Arthritis Res Ther 2016;18:82. 2. Park W, Yoo DH,
Jaworski J, et al. Comparable long-term efficacy, as assessed by patient-
reported outcomes, safety and pharmacokinetics, of CT-P13 and reference
infliximab in patients with ankylosing spondylitis: 54-week results from the
randomized, parallel-group PLANETAS study. Arthritis Res Ther 2016;18:25.
3. Yoo DH, Prodanovic N, Jaworski J, et al. Efficacy and safety of CT-P13
(biosimilar infliximab) in patients with rheumatoid arthritis: comparison
between switching from reference infliximab to CT-P13 and continuing CT-
P13 in the PLANETRA extension study. Ann RheumDis 2016; Epub ahead of
print. 4. Park W,Yoo DH, Miranda P, et al. Efficacy and safety of switching from
reference infliximab to CT-P13 compared with maintenance of CTP13 in
ankylosing spondylitis: 102-week data from the PLANETAS extension study.
Ann Rheum Dis 2016; Epub ahead of print.
A clear reflection
of innovation, accessibility,
and efficacy
A clear reflection of what has been added to the treatment paradigm.
Evidence based switching,
Evidence supports biosimilar infliximab, Remsima.
HCREM-01PB-0516

2. infliximab are highly comparable. Based on this ev-
idence, Remsima® was approved by the European
Medicines Agency and U.S. Food and Drugs Admin-
istration to treat all disorders that reference infliximab
is approved for, including active rheumatoid arthritis,
active ankylosing spondylitis, moderate-to-severe ul-
cerative colitis, moderate-to-severe Crohn’s disease,
active psoriatic arthritis and moderate-to-severe
plaque psoriasis.
PLANETRA and PLANETAS
EXTENSION STUDIES
Patients who completed the 54-week PLANETRA
(rheumatoid arthritis) and PLANETAS (ankylosing
spondylitis) randomized studies were invited to par-
ticipate in 1-year extension phases. During the ex-
tension studies, all patients received 6 infusions of
Remsima® from week 62 to week 102 (3 mg/kg for
patients with rheumatoid arthritis or 5 mg/kg for
patients with ankylosing spondylitis). In the PLAN-
ETRA extension study, 158 patients previously ran-
domized to Remsima® continued treatment, and
144 patients previously randomized to reference
infliximab switched to Remsima®. In the PLANETAS
extension study, 88 patients previously randomized to
Remsima® maintained treatment, and 86 patients pre-
viouslyrandomizedtoreferenceinfliximabswitchedto
Remsima® (Figure 1).
The demographic and disease characteristics of
patients in the Remsima® ‘maintenance’ and ‘switch’
groups were broadly comparable in each study. It is
noteworthy that the vast majority of these patients
(approximately 90%) completed all 48 weeks of treat-
ment with Remsima® in the extension studies to re-
ceive a total of 102 weeks of therapy. 3,4
In the PLANETRA extension study, American Col-
lege of Rheumatology (ACR) 20 response rates (i.e.
20% improvement in core disease measures) were
maintained at the levels observed previously in the
randomized phase of the study (Figure 2). ACR20 re-
sponse rate in the switch group at week 102 of treat-
ment was 71.8%, which was highly comparable to
that observed in the maintenance group, comprised
of patients who had received a total of 102 weeks of
Remsima® (71.7%).3
Similarly, in the PLANETAS extension study, com-
parable proportions of patients in the maintenance
and switch groups achieved responses for ASAS20,
ASAS40 and ASAS partial remission (PR) during the
extension phase (Figure 3). Furthermore, the re-
sponse rates which were observed after 102 weeks
of treatment, were similar to those seen at earlier
timepoints in the randomized study including during
treatment with reference infliximab before patients
switched to Remsima®.4
Development of antidrug antibodies (ADAs) in
patients treated with reference infliximab and other
TNF inhibitors has been widely documented. ADAs
are associated with loss of response to treatment
as well as side effects such as infusion-related reac-
tions. In PLANETRA and PLANETAS, the proportion
of patients who developed ADAs was similar in the
Remsima® maintenance and switch groups and did
not appear to increase during the course of the ex-
tension phases. Importantly, when patients were
subgrouped according to their ADA status, ACR20
response was maintained over 102 weeks of treat-
ment in ADA-positive as well as ADA-negative pa-
tients, and the proportion of patients achieving
ACR20 response was comparable in the Remsima®
maintenance and switch groups.3
Similarly, in the
PLANETAS study, ASAS20 response rates were main-
tained during the extension phase in ADA-posi-
tive as well as ADA-negative patients in both the
Remsima® maintenance and switch groups (Figure
4).4
In the maintenance and switch groups of PLANET-
RA and PLANETAS, there were no notable differences
in other measures of efficacy, and treatment effects
were maintained throughout 102 weeks of therapy.
Furthermore, the proportion of patients achieving
remission or low disease activity based on ACR/EU-
LAR remission criteria (Boolean-based definition and
index-based definition) in PLANETRA, was similar be-
tween the maintenance and switch groups through-
out the extension study.
weeks with
1:1 Randomization
Reference infliximab (RA: 3mg/kg, AS: 5mg/kg) Remsima® (RA: 3mg/kg, AS: 5mg/kg)
Week 30Week 14 Week 54 Week 78 Week 102
Switch
Maintenance
Administration period (double-blind)
Remsima® (RA: 3mg/kg, AS: 5mg/kg)
54-Week main study Extension study
Figure 1. PLANETRA and PLANETAS study design. All patients who enrolled in the extension study (RA: n=158 and 144 in the mainte-
nance and switch groups, respectively, AS: n=88 and 86 in the maintenance and switch groups, respectively) were included
in the ITT population. 3,4
Figure 2. The proportion of patients with ACR20 response was maintained for 102 weeks with Remsima® (PLANETRA)3
Randomized phase
ACR20responders,%
100
20
40
60
80
0
Week 30
76.3 77.5
Week 14
74.3 73.9
Week 54
77.0 77.5
Week 78
71.7 72.8
Week 102
71.7 71.8
Maintenance Switch
Extension phase
Figure 3. The Assessment of SpondyloArthritis (ASAS) response rates were comparable for patients who received Remsima® for 102
weeks and those who switched to Remsima® from reference infliximab (PLANETAS)4
Responders,%
100
20
40
60
80
0
ASAS20
74.1 70.175.6 77.1 80.7 76.9
ASAS40
58.0 57.5
63.9
53.5 51.8
61.5
ASAS PR
17.0 20.717.4 19.3 19.3 23.1
Maintenance Switch
Odds ratio
(95% CI)
Week 54 Week 78 Week 102
0.75
(0.38-1.48)
0.66
(0.33–1.32)
1.25
(0.58–2.70)
Week 54 Week 78 Week 102
1.20
(0.66-2.18)
1.25
(0.68–2.31)
1.09
(0.57–2.07)
Week 54 Week 78 Week 102
1.00
(0.45-2.20)
1.08
(0.51–2.31)
0.80
(0.37–1.72)