IAS_NetworkNewsletter

www.joinIAS.com
psoriasis
psoriatic arthritis
rheumatoid arthritis
spondyloarthritis
crohn’s disease and colitis
optimizing
interdisciplinary care
for the management
of imids
t h e o f f i c i a l p u b l i c a t i o n o f t h e
LLC,
TM
an HMP Communications Holdings Company
STEPHEN I. KATZ,
M.D., PH.D.
Director
National Institute
of Arthritis and
Musculoskeletal and
Skin Diseases
APRIL 1–3, 2016
Marriott Marquis
New York, NY
2 01 6 K EY N OT E PRES ENTER

2 Attend the nation’s leading conference on interrelated autoimmune diseases:
Register at joinias.com
The Interdisciplinary Autoimmune Summit (IAS) is the only event of its
kind to bring together experts and specialists from across the autoim-
mune disease spectrum to better understand how to collaboratively treat
patients with interrelated diseases, including: Psoriasis, Psoriatic Arthritis,
Rheumatoid Arthritis, Spondyloarthritis, Crohn’s Disease and Colitis.
Read through this special issue featuring content highlights
from the 2015 Summit, and then plan to join us in 2016 to
engage with leading experts, advance your knowledge
of IMIDs and improve patient outcomes.
Join a new conversation about IMIDs –
April 1-3, 2016 in New York – one that’s
collaborative, integrated and innovative.
IN THIS ISSUE
 Clinical Trials vs. 3–5
Real-World
Across Disciplines
 Optimizing 6–7
Interdisciplinary
Care for the
Management
of IMIDs
 Update on 8–11
Biosimilars:
Substitution,
Interchangeability,
and Extrapolation
of Indications
psoriasis
Inflammatory Bowel Disease

3
I
n late June at the 2015 Inter-
disciplinary Autoimmune Sum-
mit, Leonard Calabrese, DO, Joel
Gelfand, MD, MSCE, and Stephen
Hanauer, MD discussed the challeng-
es in determining efficacy versus ef-
fectiveness in immune-mediated in-
flammatory disease treatment across
the realms of rheumatology, derma-
tology, and gastroenterology.
Predictable, Unpredictable, and
Paradoxical Toxicities
Given the chronic nature of im-
mune-mediated inflammatory dis-
eases, clinicians must be vigilant in
monitoring the safety of these agents
in the long-term environment. Ad-
verse events (AEs) can be predictable,
unpredictable, or even paradoxical.
As such, familiarity with the ba-
sic mechanisms of action (MOA) of
these agents can lead to enhanced
patient care.
Biologic agents were first created
in the late 1800s.To date, more than
3 million patients have received a
TNF antagonist, and safety issues are
still being reported, largely due to
the challenges in determining drug
toxicity. The World Health Organi-
zation (WHO) classifies toxicities as
‘common’ if they occur in 1 in 100
people, ‘rare’ if they occur in 1 in
1,000 people, and ‘extremely rare’ if
they occur in 1 in 10,000 people. As
described by Dr. Leonard Calabrese:
“The rule of three suggests that you
need a study of at least 3,000 patients
to have a 95 percent confidence in-
terval to identify a safety event that
occurs in a frequency of one to a
thousand.”
There are now several tools avail-
able to help epidemiologists ac-
curately evaluate long-term safety,
including randomized controlled
trials (RCTs) comparing the agent
in question to a placebo, open-la-
bel safety extension trials, registries
or observatories, and postmarketing
follow-up. Dr. Calabrese noted that
RCTs are important, but problemat-
ic, due to the limited scope of tox-
icity analysis, sort duration, and high
drop-out rates in the placebo group.
In addition, they are not powered for
AEs, so the data that is captured does
not truly reflect the nature of this
endpoint. Registries offer additional
data, but are confounded by indica-
tion, vary in the degree of follow-up
and are not controlled for bias.
Predictable toxicities are those in-
fections and noninfectious events
occurring in alignment with evi-
dence from the preclinical model.
An example of a predictable AE is
tuberculosis granuloma in association
with infliximab, a TNF antagonist.
Unpredictable toxicities occur with-
out evidence from preclinical mod-
els. An example of an unpredictable
toxicity is progressive multifocal leu-
koencephalopathy (PML) associated
with the multiple sclerosis drug na-
talizumab. Paradoxical AEs are more
varied. Examples include incidences
of granulomatous disease, psoriasis,
and autoimmune-associated phe-
nomena in association with TNF in-
hibitor therapy. Clinicians who treat
immune-mediated inflammatory dis-
eases with biologics should familiar-
ize themselves with basic and clinical
immunology for improved patient
care and enhanced awareness of un-
predictable and paradoxical AEs.
Psoriasis Treatment
Comparative effectiveness research
(CER) is defined as research compar-
ing the benefits and harms of vari-
Clinical Trials vs.
Real-World Across Disciplines
Get the latest autoimmune updates when
you subscribe to IAS e-news – sign up at joinias.com

4 To learn more about IAS 2016, visit joinias.com or call 800-217-8801
ous interventions and strategies for
preventing, diagnosing, treating, and
monitoring health conditions in re-
al-world settings. Comparative effi-
cacy is not synonymous with effec-
tiveness (Figure). Efficacy is utilized
in a short-term, clinical trial setting
as a measure of endpoints, where-
as effectiveness is assessed through
the treatment of patients in the real
world.The purpose of CER is to im-
prove health outcomes by developing
and disseminating evidence-based in-
formation to patients, clinicians, and
other decision makers about which
interventions are most effective for
which patients under specific cir-
cumstances.
Current comparative efficacy stud-
ies of systemic treatments for psori-
asis are primarily small-scale, short-
term studies, which provide only a
“small snapshot” on the nature of the
drug in question. Indirect compar-
ative efficacy studies via meta-anal-
yses provide more information. In
these studies, the authors define drug
equivalence as a difference in efficacy
of 25 percent or less.Translating this
definition into a clinical trial setting,
Dr. Gelfand noted:“if you had a drug
that had 75 percent response rate, an-
other drug had a 55 percent response
rate, they consider those drugs equiv-
alent.” Hence, some argue that this
margin is too generous, particularly
for psoriasis treatments.
To address gaps in psoriasis CER,
the Dermatology Clinical Effective-
ness Research Network (DCERN) has
been developed to evaluate the com-
parative effectiveness of therapies in
patients currently or previously treated
for moderate to severe psoriasis. In a
DCERN analysis of patients on sys-
temic or photo therapy for moderate
to severe psoriasis (N=713), durable
response rates were found to be much
lower in clinical practice compared to
RCTs. Dr. Gelfand attributed this oc-
currence to the extended treatment
times of patients in the clinic (about a
year on average) as opposed to a clin-
ical trial, which observes patients over
a relatively short period of time. The
DCERN study also revealed subopti-
mal real-world dosing and significant
differences in adjusted response rates in
patients receiving various biologics.
When discussing long-term psoria-
sis control, persistence, adherence, and
drug survival are all integral measures.
Treatment success can also be evaluated
in terms of effectiveness,tolerability,and
patient satisfaction. As major advances
are made in the therapeutic armamen-
tarium for moderate to severe psoriasis,
it is important to remember the effec-
tiveness data is limited until short-term
efficacy data is further evaluated.
Biologics in IBD
Clinical practice represents a sig-
nificantly different environment from
clinical trials, consisting of a more
heterogeneous patient population,
modifiable treatment regimens, indi-
vidualized patient schedules and more
variable treatment outcomes that rep-
resent effectiveness (versus efficacy).
Clinical trials of biologics in irritable
bowel disease (IBD) indicate that high
dose induction and maintenance ther-
apy reduces the percentage of patients
who develop anti-drug antibodies
(ADAs).Dr.Hanauer provided the fol-
lowing example: “if you give a single
dose, about 60 percent of patients will
develop antibodies. If you give high
dose induction and continuous main-
tenance therapy, that [number] reduc-
es to about 13 percent in clinical trial.”
Trials have also demonstrated that the
number of responders achieving clini-
cal remission declines over time.
Clinical trials to assess the impact
of concomitant immunosuppressant
therapy versus monotherapy yielded
no difference in outcomes, but it is
important to note that the trials were
not powered for these factors. Alter-
nately, the Study Of Nevi In Children
(SONIC) trial consisting of Crohn’s
disease patients randomized to receive
“Very
interesting.
Great
networking.
Cutting-edge
education.”
Efficacy Effectiveness
How well does it work in ideal
settings (clinical trials)?
How well does it work in real-world
use (routine clinical practice)?
Stringent patient selection criteria to
optimize safety
Patient population is more susceptible
to AEs
Highly motivated patients with strict
adherence to research protocol
Variations in patient motivation and
ability to adhere to prescribed regimen
Highly trained physician
investigators with expertise in the
study drug
Variation in experience and
knowledge of the drug by prescriber
Clinical response determined at
arbitrary “short-term” time point
Clinical response determined in
routine clinical visits
Maximize internal validity Maximize external validity
Comparative Efficacy versus Effectiveness

5
either azathioprine alone, infliximab
alone,or combination therapy revealed
higher percentages of patients achiev-
ing clinical remission in the combi-
nation therapy arm compared to the
monotherapy arm. Studies have also
shown that retreatment at least every
8 weeks maintains response through
the last dose, at which point patients
ultimately lose response.
Dr. Hanauer explained that “with
only 25 to 30 percent of patients in
remission in clinical trials and less
than 50 percent of patients still in
remission in clinical practice,” it is
clear that improvements in treatment
are needed. In clinical practice, about
40 percent of patients require dose
escalation, and a substantial num-
ber of patients stop therapy despite
switching biologics. Treatment re-
sponse also appears to decrease with
each switch of biologic therapy. Sci-
entists are also evaluating factors that
predict response.Trough levels of in-
fliximab may be a better predictor of
continued response than ADAs. It has
also been determined that infliximab
trough levels in CD patients are cor-
related with mucosal healing.
When these and other IBD study
data are combined, it is clear that a
host of factors influence the pharma-
cokinetics of TNF antagonists. As a
result, Dr. Hanauer advised that “the
first thing … to assess when a pa-
tient is losing response to a biologic
is whether or not they’re really losing
response.” As such, alternate causes of
symptoms should first be ruled out.
The presence of ADAs may necessitate
switching ofTNF antagonists, and low
trough levels can be managed with in-
creased dose (although it is not yet de-
termined whether monitoring trough
levels and maintaining therapeutic
response is associated with improved
outcomes). However, even with these
measures, response to biologics is less
than optimal, and additional trials are
greatly needed to determine how to
best use these agents. n
2015 Participating Organizations
Included:
Cleveland Clinic (OH)
University of Pennsylvania Hospital (PA)
Weill Cornell Medical College (NY)
Brigham and Women’s Hospital (MA)
Clinic for Rheumatic Diseases (AL)
Marshfield Clinic (WI)
International Foundation for
Autoimmune Arthritis (AZ)
Mount Sinai Roosevelt Hospital (NY)
Peace Health Medical Group (OR)
Queen’s University (Canada)
Save $100 on IAS 2016 with the promo code: IASN100
Attendees
ranked
“networking
with experts
in the field,”
and “gaining
new knowledge
that facilitates
optimal patient
outcomes,” as
the top reasons
they participate
in IAS.

6 Attend the nation’s leading conference on interrelated autoimmune diseases:
D
uring the 2015 Interdisciplinary
Autoimmune Summit in New
York, Anthony Fernandez, MD,
PhD, and M. Elaine Husni, MD, MPH
discussed strategies for diagnosing
and managing psoriasis and psoriatic
arthritis (PsA), as well as the benefits
of optimized interdisciplinary care. A
case study was included to elucidate
the finer points of these topics.
Psoriasis and Psoriatic Arthritis
Psoriasis, a common chronic im-
mune-mediated skin disease, is charac-
terized by overexpression of proinflam-
matory cytokines includingTNF-alpha,
IL-17 and IL-23.Psoriatic arthritis (PsA)
is a chronic inflammatory arthropathy
associated with psoriasis. Identifying
those with psoriasis who are at high-
est risk for PsA can be challenging. Dr.
Husni explained: “There is a long lag
between those that get skin psoriasis and
when they develop the joint disease lat-
er in time.There are some times when
we can work with our dermatology col-
leagues to see if we could be better at
detecting … which of these people are
ultimately going to come out with the
joint disease as well.”
There are five subtypes of PsA: 1)
oligoarticular asymmetrical PsA, 2)
polyarticular PsA,3) distal predominant
pattern PsA, 4) spondylitis, and 5) ar-
thritis mutilans.There are also subtypes
of cutaneous plaque psoriasis, such as
guttate psoriasis, pustular psoriasis, in-
verse psoriasis, and erythrodermic pso-
riasis. PsA is difficult to define. The
CASPAR criteria for the diagnosis of
PsA assign a point system to different
characteristics that are suggestive of a
PsA diagnosis. PsA is diagnosed when
three or more points are assigned in the
presence of inflammatory articular dis-
ease (See figure on page 4).
Enthesitis can help to distinguish
PsA from other autoimmune disease,
as it occurs in 30% to 50% in PsA pa-
tients. It most commonly affects the
plantar fascia (9%), finger flexor ten-
dons (7%), and Achilles tendon (7%).
A small study of 45 psoriasis patients
revealed that 39.2% had some degree
entheseal involvement. Enthesitis in-
dices vary from 6 sites (in the Leeds
Enthesitis Index) to 18 sites (in the
Spondyloarthritis Research Consor-
tium of Canada index).A unique pop-
ulation of T cells appears to reside in
the area where the tendon and bone
meet, and these T cells have been im-
plicated in the pathogenesis of PsA.
Psoriasis occurs in patients who have
a genetic predisposition to the disease
who are then exposed to some other
trigger that activates cells of the innate
immune system including keratinocytes,
hepatocytes,or dendritic cells to express
proinflammatory cytokines including
TNF-alpha and the interferon-gamma
to activate myeloid dendritic cells.TH1
andTH2 cells then cause IL-12 and IL-
23 to produce additional proinflamma-
tory cytokines that activate keratinocytes
to increase production of antimicrobial
peptides,express other proinflammatory
cytokines and express chemokines that
feedback on the innate immune system.
This creates a “vicious loop of inflam-
mation” that has been difficult to inter-
rupt.This causes inflammation through-
out the dermis, edema, dilated blood
vessels, and activated keratinocytes that
create epidermal thickening.
The diagnosis of PsA can be diffi-
cult. A single-center study has revealed
that approximately 41% of patients who
present with musculoskeletal pain and
psoriasis have PsA. The PsoriaticArthri-
tis Screening and Evaluation (PHASE)
questionnaire has since been developed
for dermatologic populations to deter-
mine when referral to a rheumatologist
is recommended. It has a sensitivity of
93% and a specificity of 80%.
TNF Inhibitor-Induced Psoriasis
TNF inhibitor-induced psoriasis
occurs in up to 5% of patients treated
with these agents. It typically occurs in
patients who are treated for conditions
other than psoriasis and have no medical
history of psoriasis (with a median time
to onset of 9-15 months following treat-
ment initiation). There are no known
risk factors for this phenomenon, and
psoriatic lesions can vary in morphol-
ogy from plaque-type and palmoplantar
pustolosis (the most common types) to
scalp psoriasis with alopecia.Those with
known psoriasis will tend to develop
new lesions in new locations with novel
morphologic characteristics. Still, it can
be “hard to differentiate between a pa-
tient losing efficacy with the medicine
as opposed to [TNF inhibitor-induced]
eruptions.” A variety of histologic pat-
terns have also been observed, the most
common of which mimic idiopathic
psoriasis. Eosinophils and plasma cells
have been described, which may serve
as diagnostic clues.
The pathogenesis of TNF inhibi-
tor-induced psoriasis is currently un-
known, but the most prevalent hypoth-
esis is that it is caused by disruption
of cytokine balance because of the
TNF-alpha blockade, which results in
unopposed interferon alpha production
and increased expression of CR3 ligands
on keratinocytes. Myxovirus-resistance
Optimizing Interdisciplinary Care for
the Management of IMIDs

7
indicated the conference
increased their knowledge
of and confidence in treating
IMIDs.
source: 2015 Attendee Survey
95%
protein A (MxA) expression, a marker
for type 1 interferon production, has
also been shown to be higher in TNF
inhibitor-induced psoriasis compared to
typical psoriasis.
The outcome of this phenomenon is
variable; some cases will resolve without
interruption of TNF inhibitor, some can
be controlled with intervention, some
will resolve only after discontinuation,
and some may even persist despite discon-
tinuation.There is no adjuvant treatment
known that can prevent this reaction and
no treatment guidelines, so practitioners
must rely on“common sense.”
“If the psoriasis is significantly af-
fecting the patient’s quality of life and/
or it is severe, and TNF inhibitor is not
optimally treating the underlying dis-
ease for which he was prescribed, then
it makes sense to stop at TNF inhibitor
and choose an alternative treatment.
On the other hand, if it’s significant-
ly affecting quality of life or severe
[in nature] but that TNF inhibitor is
effectively controlling the underlying
disease…then it’s reasonable to try to
treat the psoriasis former reaction be-
fore resulting to removing that TNF
inhibitor.”
Patients who are unable to continue
their currentTNF inhibitor or who have
significant involvement after continu-
ation can be treated with ustekinumab,
an IL-12/23 monoclonal antibody.New
classes of IL-17 and JAK inhibitors may
also be considered in these cases.
In conclusion, collaboration be-
tween dermatology and rheumatology
clinicians optimizes care for patients
with complex inflammatory diseases,
as well as allows clinicians to gain ad-
ditional insight on disease character-
istics and creates an environment that
fosters research opportunities. n
CASPAR Criteria for the Diagnosis of PsA
PsA is diagnosed when ≥3 points below are assigned in the presence of inflammatory
articular disease (joint, spine, or entheseal)
Category Description Points
Current psoriasis or personal or
family history of psoriasis
Psoriatic skin or scalp disease confirmed by dermatologist
or rheumatologist; history of psoriasis from patient, family
physician, dermatologist, rheumatologist, or other qualified
practitioner; patient-reported history of psoriasis in first- or
second-degree relative
2
1
Psoriatic nail dystrophy on
current physical exam
Includes onycholysis, pitting, and hyperkeratosis 1
Negative for RF Enzyme-linked immunosorbent assay or nephelometry
preferred (no latex) using local laboratory reference range
1
Current dactylitis or history of
dactylitis documented by
a rheumatologist
Swelling of entire digit 1
Radiographic evidence of
juxtaarticular new bone formation
Ill-defined ossification near joint margins excluding
osteophyte formation, on plain x-rays of hand or foot
1

8
Biosimilar Guidelines and Regulations
B
iosimilars, biopharmaceuticals
that have been engineered to be
highly similar but not identical to
the reference product, are not con-
sidered to be generic drugs and must
therefore undergo a biological license
application process. The European
Union and the United States have
comparable regulatory definitions of
biosimilars. In the United States, a bi-
osimilar is a biological product that is
highly similar to the reference prod-
uct, with no clinically meaningful
differences in terms of safety, purity
and potency of the product.
Guidelines requiring comparison of a
biosimilar to the reference product were
developed in 2006 by the European
Medicines Agency (EMA). Under these
guidelines, biosimilars must demon-
strate highly similar pharmacokinetics
(PK), pharmacodynamics (PD), struc-
ture, safety, and efficacy in human tri-
als. In most cases, head-to-head clinical
trials are needed to demonstrate clinical
equivalence between the biosimilar and
an approved reference product.
In 2012, the EMA issued guidelines
on biosimilars and monoclonal anti-
bodies which are comparable to the
general guidelines, but with modifi-
cations to reduce the size and num-
ber of animal studies and streamline
the design of clinical testing in pa-
tients (i.e., a randomized, controlled
trial to demonstrate clinical efficacy
and a non-inferiority trial, paired
with 1-year follow-up immunoge-
nicity data for biopharmaceuticals
intended for chronic administration).
Comparisons can be difficult, how-
ever, in cases where the mechanism
of action (MOA) of a specific drug
varies for the treatment of different
diseases. The 2009 Biologics Price
Competition and Innovation (BPCI)
Act dictated that consideration for an
abbreviated biological license appli-
cation requires that a biosimilar and
reference product must have the same
MOA, route of administration, dos-
age form, and potency. With regard
to agents such as rituximab, a TNF
inhibitor, biosimilar comparisons for
each disease state for which the drug
is indicated must be conducted inde-
pendently. In 2012, however, the FDA
allowed extrapolation of data from a
clinical trial of a biosimilar conduct-
ed in one therapeutic area to support
approval for additional indications for
which the reference product is already
licensed. As a result of this data ex-
trapolation, in March 2015 the FDA
approved the first biosimilar agent in
the US, filgrastim-sndz. Still, an im-
portant, ongoing question revolves
around inflammatory diseases. As
noted by Jonathan Kay, MD, at the
Interdisciplinary Autoimmune Sum-
mit held June 27-29 in New York:
“Instead of requiring the manufac-
turer and biosimilar to go through
clinical trials in all eight indications
for which infliximab is approved, the
EMA [and FDA] suggest that these
studies should be done in that dis-
ease which is most responsive to the
reference part or the most likely to be
able to show differences between the
reference part within the biosimilar
where differences do exist ... I would
disagree with that part of this guidance.”
Update on Biosimilars:
Substitution, Interchangeability, and
Extrapolation of Indications
“Simply put:
Time well
spent.”
To learn more about IAS 2016, visit joinias.com or call 800-217-8801

9
Immunogenicity
An ongoing challenge with bi-
ologics is the development of im-
munogenicity. The formation of
anti-drug antibodies (ADAs) can
decrease trough levels and clinical
response. Likewise, ADA titers are
higher in nonresponders compared
with responders.
In a phase 1 trial of CT-P13, a bio-
similar infliximab, 250 patients with
ankylosing spondylitis were random-
ized to receive 5 mg/kg CT-P13 or
infliximab. This study met the pri-
mary endpoint, which was the ratio
of geometric means of PK parame-
ters with 90% confidence intervals,
and efficacy and safety parameters
were comparable between groups.
In a phase 3 trial of CT-P13, 606 pa-
tients with active rheumatoid arthri-
tis receiving methotrexate were ran-
domized to receive 3 mg/kg CT-P13
or infliximab.The primary endpoint
of this study, ACR20 at week 30,
was met, and secondary endpoints
(ACR50/70, frequency of adverse
events) were similar between groups.
ADAs can develop in patients
treated with the reference biolog-
ic or the biosimilar. Most are not
neutralizing but small differences
between the biosimilar and the ref-
erence biologic might result in in-
creased immunogenicity with inter-
change. Studies of ADA assays cannot
be compared directly, but the most
recent trials of CT-P13 found 50%
ADAs at 54 weeks and another study
at 54% at 52 weeks. Importantly, a
much higher proportion of patients
developed ADAs with the lower
dose in rheumatoid arthritis despite
methotrexate therapy than with a 5
mg/kg monotherapy in ankylosing
spondylitis.
Interchangeability, Switching, and
Substitutions
According to the BPCI Act, for
a product to be interchangeable, it
must be a biosimilar to the reference
product and be expected to produce
the same clinical result. In addition,
the safety and diminished efficacy
risks associated with alternating or
switching between the biosimilar
Transition study
Substitution study (single switch)
Interchangeability study (multiple switches)
Switching versus substitution in clinical trials
“The Interdisciplinary
Autoimmune
Summit provides an
opportunity to create
cross-talk between the
medical subspecialties
that focus on
immune-mediated
inflammatory
diseases. While the
epidemiology and
immune-inflammatory
pathways overlap, we
can learn from our
mutual successes (and
failures) as to how to
optimize management
of these chronic
diseases.”
Stephen B. Hanauer, MD
2016 IAS Co-Chair
Clifford Joseph Barborka
Professor of Medicine
Northwestern Feinberg
School of Medicine
Medical Director,
Digestive Health Center
Chicago, Illinois
found the products and
services in the IAS expo to
be of value to their work.
77%
Save $100 on IAS 2016 with the promo code: IASN100

10
and the reference product must not
be greater than the reference prod-
uct alone. The problem with this,
according to 2015 Interdisciplin-
ary Autoimmune Summit presenter
Brian Feagan, MD, FRCPC, is that
interchangeability will, if granted,
allow someone other than the pre-
scriber to substitute the biosimilar
for the reference product.
The definition of a ‘switch’ is a tran-
sition to a biosimilar after initial treat-
ment with a reference product; this
requires a single switch study. Alter-
nately, a ‘substitution’ or ‘interchange’
describes switching back and forth be-
tween the reference product and bio-
similar. Study designs for transitioning,
substituting, or interchanging refer-
ence products are pictured (page 9).
Interchangeability studies are lim-
ited by the undefined number of
switches needed to prove interchange-
ability, as well as ethics surrounding
potential additional risks to subjects.
In Norway, the government nego-
tiates the price of intravenous med-
ications on an annual basis. In 2010,
CT-P13 was priced 39% lower than
the reference product. As a result, all
Norwegians received CT-P13 for one
year.The Nor Switch study is current-
ly evaluating the safety and efficacy of
switching from infliximab to the bio-
similar. In the interim, balancing the
potential risks of a biosimilar with the
lower cost and wider availability of
these products is an ethical issue that
continues to be debated.
Immunogenecity in Monoclonal Antibodies
The efficacy of monoclonal anti-
bodies is greatly impacted by pharma-
cokinetics and immunogenicity. The
development of ADAs and correlation
of these antibodies with clinical re-
sponse and risk of infusion reaction
was confirmed in 2003 by Baert et
al. Immunogenicity—and diminished
plasma drug concentration—has since
been found to occur in a large pro-
portion of patients within the first 12
to 16 weeks of monoclonal antibody
therapy; inadequate drug concentra-
tions have a negative effect on efficacy,
as well as drug continuation.
An example of extreme immuno-
genicity is Pure Red Cell Aplasia, a
condition where the body’s immune
system becomes sensitized against
erythroblasts in the bone marrow. Be-
tween 1998 and 2002, over 200 cases
of Pure Red Cell Aplasia were report-
ed in association with erythropoietin
use in dialysis patients.After 2 years of
investigation, it was determined that
a manufacturing change in the plas-
ticizer in the stoppers resulted in ad-
juvant activity and the formation of
ADAs. This phenomenon “shows that
manufacturing processes can have un-
pleasant effects and low and behold…
there is a biosimilar erythropoietin in
Thailand and there has been an out-
break of pure red cell aplasia with
that product.” The sudden epidemic
of Pure Red Cell Aplasia underscores
the complexity of immunogenicity in
biosimilars.
“This is a very
unique event. As a
rheumatologist, I
really enjoyed the
perspectives of the
gastroenterologists
and dermatologists
I engaged with.”
Thomas J. Romano, MD, PhD
NEW! IAS 2016
will feature:
 Industry Roundtable:
A panel of leading
executives in the
autoimmune space
will share insight
and perspective on
the future of IMID
care: approaches,
treatments, and more
 A variety of networking
opportunities to
enhance cross-specialty
engagement and
learning
 Shorter presentations
covering hot topic areas
to elevate attendee
knowledge
IAS2016
Attend the nation’s leading conference on interrelated autoimmune diseases:

11
Gel and Coomb’s Classification of Hypersensitivity and Autoimmune Diseases
would recommend IAS to
a colleague or friend.
94%
Extrapolation and Interchangeability in
Monoclonal Antibodies
Althought there are TNF antag-
onists on the market, it has been
demonstrated in 2007 by Nesbitt et
al. that there are significant differ-
ences in cell sigmoid and cytokine
patterns between these agents, sug-
gesting that conformational changes
in the receptor can result in different
biological effects. This phenomenon
was observed in a 2001 trial by Sand-
born et al of the rheumatoid arthritis
drug abatacept, which was found to
be largely ineffective for the treat-
ment of Crohn’s disease. This study
highlights the impracticality of ex-
trapolating clinical data for monoclo-
nal antibodies due to differences in
dose, PK, duration of therapy, etc.
Because biosimilars are not ge-
neric drugs, a risk-benefit analysis of
biosimilars—particularly monoclonal
antibodies—and potential impact on
immunogenicity is warranted. Inter-
changeability issues highlight the need
for additional safety data, and until these
issues are clarified, switching patients
from reference products to biosimilars
should be approached with caution. n

INTERDISCIPLINARY
AUTOIMMUNE
SUMMIT 2016
APRIL 1–3, 2016
N e w Yo r k M a r r i o t t M a r q u i s
N e w Yo r k , N Y
the nation’s leading scientific
conference on immune-mediated
inflammatory diseases (imids)
Where Rheumatologists, Dermatologists,
Immunologists and Gastroenterologists
connect to develop collaborative care
guidance to treat patients with:
psoriasis
psoriatic arthritis
spondyloarthritis
crohn’s disease and colitis
“countless
clinical pearls
embedded in
a matrix of
sound science
and medicine
SAVE $100 WITH
PROMO CODE: IASN100
Visit: www.JoinIAS.com
Call: 800.217.8801
”

IAS_NetworkNewsletter

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (18)

Similar to IAS_NetworkNewsletter

Similar to IAS_NetworkNewsletter (20)

IAS_NetworkNewsletter