The Efficacy of Biological Therapies for Psoriasis - Review Article

ISSN 2349-7823
International Journal of Recent Research in Life Sciences (IJRRLS)
Vol. 3, Issue 1, pp: (1-4), Month: January - March 2016, Available at: www.paperpublications.org
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Paper Publications
The Efficacy of Biological Therapies for
Psoriasis -Review Article
1
Fahad K. ALSudairy, 2
Saad F. Almashan
1
Consultant Dermatologist and Dermatological Surgeon, Prince Sultan Medical Military City, Riyadh, Saudi Arabia,
Assistant Professor, Faculty of medicine, Almaarefa Colleges, Riyadh, Saudi Arabia
2
Medical Intern. Faculty of medicine, King Saud University, Riyadh, Saudi Arabia
Abstract: Background: it is indicated that Biological Therapies has great effect in dealing with Psoriasis.
Differences in response rates of biologics for the treatment of moderate-to-severe plaque psoriasis have been
reported in many published articles.
Objective: this paper aims to declare the effectiveness of biological therapies for psoriasis.
Methods: using the search engine PubMed to prepare comprehensive literature about the specified topic.
Main results: it is indicated that psoriasis is a chronic inflammatory skin disease condition that involves altered
expression of a broad spectrum of proinflammatory cytokines which are associated with activation of T cells and
proliferation of keratinocytes.
Conclusion: The introduction of targeted biologic therapies has greatly improved the treatment options for
psoriasis although the pathogenesis of the autoimmune skin disease has not been fully elucidated. The potential for
psoriasis disease is implicit because altered expressions of cutaneous and systemic cytokines are well demonstrated
in psoriasis patients.
Keywords: psoriasis, biological, Infliximab, Efalizumab, Adalimumab, Ustekinumab, Alefacept.
1. INTRODUCTION
Psoriasis is a clear disease that has much interest. It is a chronic and immune-mediated skin disease that also has systemic
manifestations. Safe and effective treatments are required. Biologic treatments that inhibit the immunopathogenesis of
psoriasis have helped meet this need.
Psoriasis is the most prevalent immune disease in the US, affecting 2-3% of the general population. 'It is associated with
numerous systemic effects including cardiovascular disease, the metabolic syndrome, and increased risk for lymphoma.
Furthermore, up to 30% of psoriatic patients may develop psoriatic arthritis. Psoriasis can be clear and presented in the
skin by scaly skin lesions and erythematous
In a study by Iris H. Kim, et al., (2012), it is indicated that FDA-approved regimens of adalimumab, infliximab,
ustekinumab, and alefacept were effective in treating moderate-to-severe psoriasis. It is weighted in the range of PASI-75
scores for infliximab, ustekinumab, alefacept adalimumab, and etanercept are 78.6%, 72.1%, 70.5%, 48.1%, and 21%,
gradually. In fact, this study aims to identify the Efficacy of Biological Therapies for Psoriasis.
In order to achieve the research objective, there was a great need to collect valuable information and data about the topic.
Throughout Clinical trials, they present improvements whether they are in physical or health which is related to life
quality (HRQoL) that measures in patients with psoriasis treated with biologics compared with placebo. Moreover, these
reports give few description of the meaning of Dermatology Life Quality Index (DLQI) degrees and supply few
comparisons of data.

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2. METHODOLOGY
The main methodology employed here is to use the PubMed as research engine and reviewing English articles that were
published about human subjects in order to collect the required data and information.
3. RESULTS
The following parts illustrate the main biological therapies for psoriasis. After reviewing the studies collected, it is
indicated that the most outstanding biological therapies are Efalizumab, Infliximab, Adalimumab, Ustekinumab and
Alefacept.
Efalizumab:
The studies showed that Efalizumab is considered as one of a recombinant humanized monoclonal (IgG1) antibody which
directed against the a subunit (CD11a) of LFA-1 found on the surface of T-cells, blocking LFA-1 mediated T-cell
adhesion. It is administered subcutaneously (SC), with a recommended dose of 0.7 mg/kg in the first week, followed by 1
mg/kg SC every week for the next 11 weeks. Efalizumab received its psoriasis indication in October 2003. Multiple phase
III clinical trials have assessed the safety and efficacy profile of this one , but only during 3–6 months of therapy.
Efalizumab has recently been removed from the market in Europe and has renewed warnings from the FDA because of
concerns of rare cases with increasing multifocal leukoencephalopathy after long usage.
Efalizumab has one prospective long-term trial to date in the treatment of psoriasis. Throughout this open label, it is clear
to multicenter phase III study about 339 patients with moderate-to-severe chronic plaque psoriasis were randomized into
the initial 3-month phase to receive subcutaneous efalizumab 2 mg/kg weekly, with an added randomization to receive
concomitant fluocinolone acetonide ointment or a placebo equivalent from Weeks 9 through 12. ITT analysis was
performed on the 339 participating subjects and those that did not achieve at least 50% improvement (PASI 50) were
considered non-responders and discontinued from following into the next phase. The second phase was a long term
observational period using last focus of observation can be done forward (LOCF) analysis, that patients achieving a 50%
PASI score were eligible to receive efalizumab can be taken as 1 mg / kg in a week for thirty three months. Then the final
3-month treatment period was an optional transition period for patients who completed the second phase before
efalizumab became commercially available.
Infliximab:
Infliximab is presented as Remicade; Centocor, Inc., Horsham, PA and it is a chimeric monoclonal antibody that binds
soluble and membrane-bound TNF-a approved by the FDA in 2006 for the treatment of moderate to severe psoriasis. The
recommended dosage for infliximab is 5 mg/kg IV infusion, to be administered at baseline, and then repeated at Weeks 2,
6, andthenevery8weeks(Q8W)thereafter. Whereas the infliximab effect in psoriasis has been studied in numerous clinical
trials, two phase III studies focused on the long-term efficacy of this drug in the treatment of this chronic condition.
Adalimumab:
Adalimumab was approved in January 2008 by the FDA for the treatment of plaque-type psoriasis, for which it is
managed every other week by subcutaneous injection. It is a recombinant, fully human immunoglobulin G1 (IgG1)
monoclonal antibody that related with specificity and high affinity to TNF-a (45). The majority of responses attributed to
TNF are arranged by the p55 cell surface TNF receivers. Upon binding to TNF-a, adalimumab blocks its interaction with
the p55 and p75 cell surface TNF receptors. This process of neutralization of TNF-a by a specific monoclonal antibody
should improve both skin and joint manifestations of psoriasis.
Ustekinumab:
Ustekinumab is considered as a fully human monoclonal antibody that aims at interleukin-12 (IL-12) and interleukin-23
(IL-23). It is related to high affinity to their shared p 40 sub branch , neutralizing their bioactivity by blocking interactions
with their cognate receptors. This agent thus targets Th1 and Th17 arms of immunity, both of which we now know are
pivotal in the immunopathogenesis of psoriasis.

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Alefacept:
Alefacept is considered as a fully human (LFA-3/IgG1) fusion protein that, by targeting CD2, inhibits T-cell activation
and proliferation, and induces the selective apoptosis of memory T-cells (CD45RO+) (17,18). It was the first biologic
agent to receive FDA advise as a treatment of chronic plaque psoriasis, in January 2003. The alefacept selective
immunomodulatory effect, which inhibits only the pathogenic memoryeffector T-lymphocytes, has given the agent the
perception of one of the best safety profiles among members of the biologics family. Unfortunately, this selective
mechanism of action has also resulted in a lesser short-term efficacy profile with the PASI 75 of 21% evaluated at 14
weeks of therapy (19). Little data has been published in regards with the long-term use of alefacept. Alefacept reduction
of CD4 counts has resulted in a dosing schedule that requires periods on and off of the medication. The medication is
given as a 15-mg intramuscular (IM) injection every week for 12 weeks, followed by a 12-week drug-free interval,
possibly followed by another 12-week course if there is normal CD4 count (20). This contrasts to other biologics that are
given on a continuous basis, making alefacept efficacy analysis difficult to compare with other agents. Most reports on
multiple courses of alefacept refer to a second dosing cycle. For this review, in order to consider long-term use, the
subject must have received at least three dosing cycles (12 weeks each), with their equivalent drug-free cycles adding up
to 48 weeks of therapy. It can be done through long-term use of alefacept that has been assessed in patients to participate
in phase III trials and later enrolled in extension studies. Short term analysis demonstrated that only a small proportion of
treated individuals achieve PASI 75 (21). For those who do respond, successive treatment cycles can be of added benefit,
with extensive remission periods and limited adverse effects.
4. DISCUSSION
It is indicated that despite of relation of therapy and biologic agents is widely used in the care of rheumatoid arthritis and
psoriatic arthritis, there are only a few small-scales and randomized trials that are performed in patients with psoriasis. In
many cases, studies of combination therapy with biologic agents are conducted against a background of treatment with
traditional systemic therapies, like methotrexate, in persons without a suitable response to that treatment. Moreover , a lot
of the studies were carried out in patients with psoriatic arthritis; the result of therapy on their psoriasis was also checked
as a secondary consideration. Lately, the European consensus conferences presented some recommendations for
combining biologic and traditional systemic psoriasis therapies to supply some level of structure for this practical way.
Studies have suggested that patients experience slight reductions in their clinical responses after their dosing schedule is
cut, thus the results presented by the long-term study might not reflect the clinical responses that could be obtained with a
long-term etanercept regimen, perhaps creating unrealistic expectations among physicians and patients Infliximab long-
term efficacy was demonstrated in two phase III trials (EXPRESS I and II), with clinically significant improvements. Loss
of response during the maintenance phase is not entirely understood, but may be a result of lower serum concentrations in
the maintenance phase compared with the induction phase, and the formation of neutralizing antibodies. Similar to
previous studies of biologics, efficacy data were analyzed based on an ITT analysis, which may bias the efficacy levels to
present more favorable long term results. Overall, infliximab demonstrated the greatest short-term efficacy results but had
a much more moderate effect when long-term treatment was evaluated. The long-term trials studying adalimumab
demonstrated that this biologic is highly efficacious for patients with moderate to severe plaque-type psoriasis, with
sustained clinical responses over several months of therapy.
5. CONCLUSION
The analysis illustrates that the treatment strategy for psoriasis depends on a variety of factors (e.g., the medical history,
tolerability of therapies and potential for side effects, and disease severity). Regarding disease severity, there is no
commonly accepted definition of mild versus moderate-to-severe psoriasis. Moreover, a patient may have mild disease on
the basis of body surface area (BSA) involvement, but localization of lesions in vulnerable areas (e.g., the face, feet,
hands, and/or genitals) may warrant systemic therapy. Some guidelines provide specific criteria to help evaluate the
severity of a patient’s psoriasis, but all recognize the importance of assessing both the physical and psychosocial burden
when considering the best treatment approach.

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Declaration of Interest:
The authors have no conflict of interest to declare.
REFERENCES
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[7] Jie Wang, Yow-Ming C. Wang, and Hae-Young Ahn (2014). Biological Products for the Treatment of Psoriasis:
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