Therapeutic Antibodies for Psoriasis Treatment

This essay discusses the comparative effectiveness and shortcomings of two therapeutic antibodies: Guselkumab and Secukinumab for the treatment of psoriasis. It explores their mechanisms of action, similarities and differences, efficacy results, and comparison of side effects. The essay also provides insights into the process of bringing these antibodies into the marketplace.

Running head: THERAPEUTIC ANTIBODIES FOR PSORIASIS TREATMENT
THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
Name of the Student:
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Author note:

1THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
Introduction
Psoriasis is a chronic dermal disease condition which is autoimmune in nature and is
accompanied by abnormal skin patches. Treatment interventions include topical corticosteroid
ointments, ultraviolet phototherapy as well as non-biological systemic medications (Takeshita et
al. 2017). Recently, administrations of ‘biologics’ or antibody based treatments have obtained
importance, which emphasize upon hindering the inflammatory mechanism of cytokines
(Blauvelt et al. 2017). This essay discusses on the comparative effectiveness and shortcomings
of two therapeutic antibodies: Guselkumab and Secukinumab and the process by which these
products have been introduced into the marketplace.
Discussion
Function of the Products to treat Psoriasis
Guselkumab
As researched by Gordon et al. (2015), psoriasis is characterized by the collaborative
action of keratinocytes and T cells. Amidst this interplay of interactions, the role of the axis of
interleukin (IL)-23/IL-17 is considered to be potentially contributive to the psoriasis pathology
and hence, current treatment interventions propose the strategy of selectively inhibiting
interleukin 23 – a cytokine occurring naturally with salient functions in numerous immunological
and inflammatory responses in the human body. As examined by Deodhar et al. (2018),
interactive interactions between the concerned receptor and IL 23 directs TH17 cells to
differentiate, proliferate and survive further resulting in the production of chemokines and pro-
inflammatory cytokines, which further result in an aggravation of the debilitating symptoms of

2THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
plaque psoriasis. The mechanism of action of Guselkumab is characterized by its selective
inhibition of IL 23. Guselkumab is a human antibody of the G1 lambda monoclonal type.
Guselkuminab functions through selective binding of an Il 23 subunit resulting in an inhibition
of the interactive effects between IL 23 and its concerned receptor which further results in the
prevention of chemokines and pro-inflammatory cytokines responsible for plaque psoriasis
proliferation (Reich et al. 2017). Guselkumab has received approval from the Food and Drug
Administration after successful demonstration of its therapeutic effects in three randomized
clinical trials. Guselkumab is sold under the name of ‘Tremfya’ and is available in the form of
a100 mg/ml injection, to be administered subcutaneously at 0, 4 and henceforth, after 8 weeks
(Papp et al. 2018).
Secukinumab
Authors Mease et al. (2015) researched that, individuals who are suffering from the
chronic symptomatic effects of plaque psoriasis, have been found to posses aggravated levels of
interleukin 17A in their abnormal dermal lesions. Similar to IL 23, IL 17A is a cytokine
occurring naturally and endogenously in the human body and is involved extensively in the
performance of several natural immunological and inflammatory processes. As researched by
Baeten et al. (2015), Secukinumab is a human immunoglobulin antibody of the G1 monoclonal
type. Secukinumab initiates its mechanism of action by binding selectively to the cytokine IL
17A resulting inhibition in the interaction between the concerned receptor and the former. Hence
as researched by McInnes et al. (2018), through such a selective binding and inhibition,
Secukinumab inhibits the proliferation of pro-inflammatory cytokines, epidermal neutrophils and
chemokines which are responsible for the emergence of the autoimmune dermal symptoms of
plaque psoriasis. The therapeutic antibody Secukinumab has been approved by the FDA upon

3THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
exhibition of successful results in four randomized clinical trials. At present, Secukinumab is
marketed under the name of ‘Cosentyx’, to be administered as an injection subcutaneously, at
recommended dosages of 300 mg, at 0, 1, 2, 3 and then at every 4th week. The dosage of 300 mg
is administered in the form of 2 injections at dosage concentrations of 150 mg (Sanford and
McKeage 2015).
Similarities and Differences
As researched by Bilal et al. (2018), Guselkumab and Secukinumab are similar to each
other in their therapeutic objective of treatment of the common autoimmune disorder of
psoriasis. However as researched by Robertson et al. (2018), Guselkumab has been
recommended for the treatment aimed at alleviating symptoms of plaque psoriasis occurring at
mild to severe rates. The antibody Secukinumab poses considerable differences in being
recommended as a therapeutic intervention for a wider spectrum of diseases other than psoriasis,
such as psoriatic arthritis and ankylosing spondylitits (Blauvelt et al. 2017). As examined by Al-
Salama and Scott (2018), while both antibodies are similar in the form of their monoclonal
antibody nature and target treatment objective of reducing the production of psoriasis-causing
chemokines and pro-inflammatory cytokines via selective inhibition of cytokines such as
interleukins, key differences between the two therapeutic antibodies can be observed in their
mechanisms of action. Guselkumab exerts its therapeutic mechanism of action by administering
selective inhibition of a subunit of interleukin 23. The biologic Secukinumab is different in this
aspect since it exerts selective inhibition of interleukin 17A comprehensively, and not just its
subunit (Yiu and Warren 2018). However, as researched by Sriram et al. (2016), it has been
observed that the drugs exerted considerable similarities in their consequences of negative health

4THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
outcomes in the form of exertion of common side effects such as diarrhea, herpes and infections
in the upper respiratory tract.
Efficacy: Results from the Phase 3, ECLIPSE Study
The efficacy of the therapeutic effects exerted by guselkumab in comparison to
Secukinumab was researched extensively by the ECLIPSE study performed by the Janssen
Pharmaceutical Companies of Johhson & Johnson. The third phase of the comparator trials
ECLIPSE was formulated and conducted in the form of a multicenter, randomized, double blind
research with the objective of evaluating the safety and effectiveness of Tremfya (guselkumab)
against Cosentyx (Secukinumab) among adults who were suffering from the mild to severe
symptoms of plaque psoriasis (Markham 2017). A total number of 1048 patients were
randomized into two groups, with one group receiving 10 mg of Tremfya, injected
subcutaneously at dosages of 100 mg at 0, 4 and 12 week, and then proceeding with a dosage
administration after every 8 weeks. The other group of plague psoriasis patients received
Cosentyx at a total dosage concentration of 300 mg, which was administered by injecting
subcutaneously at two dosages of 150 mg at 0, 1, 2, 3 and 4 weeks, proceeding with a dosage
administered at every 4th week (Wan et al. 2018). Calculating the proportion of patients with an
achievement of a response of 90% PASI score (Psoriasis Area Severity Index) at the 48 week
was the primary endpoint of this research whereas the secondary endpoints were evaluated at the
12th and 48th week, followed by monitoring of patiemt safety at the 56th week. Upon observation
of the results of the study, it was observed that a total of 84.4% of patients who were
administered Tremfya medications fulfilled an improvement of 90% in their scores of PASI at
the 48th week, as compared to a total of 70% of patients who were administered Cosentyx,
achieving the same 90% PASI score. Hence the results of this study demonstrated the therapeutic

5THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
efficacy of Guselkumab being superior to that of Secukinumab and was one of the first head-to-
head studies to have demonstrated the efficacies of Janssen’s Tremfya, which targeted a subunit
of IL 23, against Novartis’s Cosentyx which administered its action by selective inhibition of IL
17A (Bone et al. 2018).
Despite the comparative efficacy observed in Guselkumab as compared to Secukinumab,
both therapeutic antibodies have been documented to be biologic-based treatments of
considerable safety and effectiveness aimed as an intervention for debilitating symptoms of
psoriasis. However, there seems to be a lack of adequate discussion or comparative analysis on
the reasons governing such differences in effectiveness, for which further research is required
(Tsai and Tsai 2017). At present, as researched by Bilal et al. (2018), a number of therapeutic
antibody based treatments are available for psoriatic patients. Hence, considering the same,
further conductance of clinical trials and evidenced based researches are required for the
evaluation of the prolonged long term safety and efficiencies exerted by each of these novel and
potentially beneficial therapeutic approached for psoriasis.
Comparison of Side Effects
Guselkumab
As researched by Wechter, Cline and Feldman (2018), the primary mechanism of action
of guselkumab lies in its inhibition of proliferation of pro-inflammatory cytokines – molecules
which are play essential roles in the administration of immunological responses as a defense
mechanism against inflammation. Considering this immune lowering effect of guselkumab,
negative health outcomes may exists as consequences in patients resulting in a lowered immunity
against bacterial, fungal and viral infections (Nawas et al. 2017). Taking insights from the same,

6THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
its manufacturer, Janssen Pharmaceutical Companies recommends clinicians to perform an
assessment for the identification of tuberculosis symptoms in patients prior to the administration
of Tremfya, which may also include additional treatment for tuberculosis alleviation (Chaplin
2018). Hence, as researched by Kelsey, Chirch and Payette (2018), major side effects of
guselkumab medications include emergence of symptoms characteristic of tuberculosis such as:
frequent coughing with mucus and blood, shortness of breath, aching muscles, loss of weight,
fever, sweating, chills, stomach aches or aggravation to diarrhea and a burning sensation during
urination. Additional side effects which may emerge as a consequence of Guselkumab
medication include headaches, adverse reactions at the sites of injection administration,
acquisition of infections at the upper respiratory tract, dermal infections caused by fungal strains,
pain in the joints, gastrointestinal problems associated with diarrhea and herpes (Galluzzo et al.
2018).
Secukinumab
As researched by Schwensen et al. (2017), the side effects and adverse health outcomes
associate with the administration of therapeutic antibody Secukinumab include infections
occurring at the upper respiratory tract, gastrointestinal symptoms such as diarrhea,
inflammatory bowel disease, herpes and runny nose. Patients may also demonstrate symptoms of
intolerances and hypersensitivities upon being administered with Secukinumab resulting in an
aggravation of existing symptoms of psoriasis.
Comparison
Hence, as researchd by Bilal (2018), upon comparison of the side effects exerted by both
of the aforementioned therapeutic antibodies, it can observed that both medications administer
similar side effects in the form of hypersensitivities such as upper respiratory tract infections,

7THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
herpes, runny nose and diarrheal symptoms, possibly due to their common target mechanisms of
inhibiting endogenous molecular components required for the purpose of exerting immune
responses as a defense against infections. However, as researched by Amin et al. (2017),
differences can be observed in the increased severity of side effects administered by guselkumab,
in the form of increased patient disposition towards tuberculosis acquisition which is otherwise
absent in patients receiving Secukinumab.
From Experimentation to Marketplace
Guselkumab
The therapeutic antibody guselkumab is currently marketed under the retail name of
Tremya and was produced by Janssen. Its introduction in the marketplace was successful after it
received approval from the FDA in the year 2017. The acquisition of this approval was deemed
to be successful based on the nature of results reported by three randomized phase 3 clinical
trials known as VOYAGE 1, VOYAGE 2 and NAVIGATE, which comprised of a clinical
development program involving over 2000 patients (Griffith et al. 2018). Randomized controlled
trials of VOYAGE 1 and VOYAGE 2 consisted of a total of 1443 psoriasis participants
randomized to experimental groups receiving g 100mg of Tremfya and control groups receiving
a placebo for over 8 weeks, resulting in the higher number of patients belonging to the
experimental group achieving a clearance score 0 of IGA (Investigator’s Global Assessment) and
90% PASI score fulfillment in comparison to the control group of placebo receiving participants
(Armstrong et al. 2018).
The third randomized controlled trial of NAVIGATE was performed among 268 subjects
who had not generated adequate therapeutic responses upon being treated with ustekinumab, for

8THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
the purpose of evaluation of the effectiveness of treatment associated with Tremfya for a
duration of 24 weeks (Langley et al. 2018). The selected psoriasis subjects were randomized to
an experimental group involving switching medication treatments to Tremfya as against a control
group required to proceed with the previous medication of ustekinumab. The results reported a
similar increased proportion of Tremfya receiving patients achieving IGA clearance score of 0
and 90% score of PASI in comparison to the patients belonging to the control group, achieving
the same at the 12th week (Diels et al. 2017).
Secukinumab
The psoriasis antibody treatment of Secukinumab is currently marketed under the name
of Cosentyx and was produced by Novartis. This medication acquired approval by the FDA to
release in the marketplace after a process of reporting successful results in four randomized,
multicentre clinical trials. The trials consisted of a total of 2403 psoriasis participants who had
displayed unresponsive to psoriatic treatments of systemic or phototherapy, within the age group
of 18 years or beyond, in possession of a minimum 10% plaque psoriatic affected surface area
and a PSAI index score of 12 or beyond (Paul et al. 2015). The trials included randomization
where 691 received 300 mg of Cosentyx, 692 receiving 150 mg of Cosentyx, 694 receiving
placebo and 323 receiving and active biological control. Every trial reported successful
achievement of primary and secondary endpoints involving Cosentyx receiving patients
acquiring 75% and 90% PASI scores and 0 score indicating skin clearance in IGA screening, at
the 12th week respectively (Spindeldreher et al. 2018).

9THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
Conclusion
Guselkumab and Secukinumab have been proven to be potentially breakthrough
therapeutic approaches in the treatment of psoriasis. Despite the proven efficacies of the two,
guselkumab has been researched to be therapeutically superior in comparison to the therapeutic
effects exerted by Secukinumab, as observed in the Phase 3 ECLIPSE study. Additionally,
despite the novel treatment approach of the two, characterized by a targeted response towards
cytokine inhibition, potentially harmful side effects have been reported by both these drugs, with
guselkumab administering far greater harmful consequences in the form of possible tuberculosis.
To conclude, further researches are required for determining long term efficacies and possible
future health outcomes in the concerned patients.

10THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
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16THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
Appendix: Aide Memoire
Mechanism of Action
Guselkumab:
 The mechanism of action of
Guselkumab is characterized by its
selective inhibition of IL 23.
 Guselkuminab functions through
selective binding of an Il 23 subunit
resulting in an inhibition of the
interactive effects between IL 23 and its
concerned receptor which further
results in the prevention of chemokines
and pro-inflammatory cytokines
responsible for plaque psoriasis
proliferation.
Secukinumab:
 Secukinumab initiates its mechanism of
action by binding selectively to the
cytokine IL 17A resulting inhibition in
the interaction between the concerned
receptor and the former.
 Through such a selective binding and
inhibition, Secukinumab inhibits the
proliferation of pro-inflammatory
cytokines, epidermal neutrophils and
chemokines which are responsible for
the emergence of the autoimmune
dermal symptoms of plaque psoriasis.
Similarities and Differences
 Guselkumab and Secukinumab are similar to each other in their therapeutic objective of
treatment of the common autoimmune disorder of psoriasis.
 Guselkumab has been recommended for the treatment aimed at alleviating symptoms of
plaque psoriasis occurring at mild to severe rates. Secukinumab poses considerable
differences in being recommended as a therapeutic intervention for a wider spectrum of
diseases other than psoriasis, such as psoriatic arthritis and ankylosing spondylitits.
 Both antibodies are similar in the form of their monoclonal antibody nature and target
treatment objective of reducing the production of psoriasis-causing chemokines and pro-
inflammatory cytokines via selective inhibition of cytokines such as interleukins.
 Guselkumab exerts its therapeutic mechanism of action by administering selective
inhibition of a subunit of interleukin 23. The biologic Secukinumab is different in this
aspect since it exerts selective inhibition of interleukin 17A comprehensively, and not
just its subunit.
 Both are similar in their side effects in the form of exertion of common side effects such
as diarrhea, herpes and infections in the upper respiratory tract.
Efficacy
The results of the Phase 3, multicenter, randomized, double blind ECLIPSE study demonstrated
Guselkumab being superior to that of Secukinumab.
Comparison of Side Effects
Guselkuminab:
 Coughing with mucus and blood,
shortness of breath, aching muscles,
loss of weight, fever, sweating, chills,
stomach aches or aggravation to
diarrhea and a burning sensation during
urination.
 Headaches, adverse reactions at the
Secukinumab:
 Infections occurring at the upper
respiratory tract, gastrointestinal
symptoms such as diarrhea,
inflammatory bowel disease, herpes
and runny nose.
 Patients may also demonstrate
symptoms of intolerances and

17THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSORIASIS
sites of injection administration
infections at the upper respiratory tract,
dermal infections caused by fungal
strains, pain in the joints, diarrhea and
herpes.
hypersensitivities.
From Experimentation to the Marketplace
Guselkumab:
 Guselkumab has received approval
from the Food and Drug Administration
after successful demonstration of its
therapeutic effects in three randomized
clinical trials.
 Guselkumab is sold under the name of
‘Tremfya’ and is available in the form
of a100 mg/ml injection, to be
administered subcutaneously at 0, 4 and
henceforth, after 8 weeks
Secukinumab:
 Secukinumab has been approved by the
FDA upon exhibition of successful
results in four randomized clinical
trials.
 Secukinumab is marketed under the
name of ‘Cosentyx’, to be administered
as an injection subcutaneously, at
recommended dosages of 300 mg, at 0,
1, 2, 3 and then at every 4th week.
 The dosage of 300 mg is administered
in the form of 2 injections at dosage
concentrations of 150 mg.