Systemic treatment of psoriasis - Part II: Biologic immunomodulator agents


Em continuidade ao capítulo da edição anterior dos Anais Brasileiros de Dermatologia, nesta segunda parte da EMC-D serão discutidas as novas drogas, os imunomoduladores biológicos, que agem em determinadas fases da imunopatogênese da doença, modificando fenotipicamente sua evolução. Também serão discutidos alguns aspectos imunológicos que, atualmente, são responsáveis pelo desencadeamento da doença

psoríase; psoríase; psoríase

As part of its continued studies of psoriasis, this second part of the Continuing Medical Education in Dermatology segment of the Anais Brasileiros de Dermatologia introduces biological immunomodulators. Also known as "biologics", these drugs act on the immunopathogenetic steps of psoriasis by changing its features and progression. This paper also reviews some of the immunologic aspects of psoriasis.

psoriasis; psoriasis; psoriasis


Systemic treatment of psoriasis - Part II: Biologic immunomodulator agents* * Work done at "Hospital Celso Pierro, Pontifícia Universidade Católica de Campinas - PUC"

Lúcia ArrudaI; Sylvia YpirangaII; Gladys Aires MartinsIII

IDermatology specialist, Master's Degree in Dermatology, Professor of Dermatology, Medical Faculty; Head of the Dermatology Service and Coordinator of the Ambulatory Psoriasis Center of Celso Pierro Hospital and Maternity, PUC-Campinas

IIDermatology Specialist, Master's Degree, Assistant M.D., Dermatology Service, Celso Pierro Hospital and Maternity, PUC-Campinas

IIIVoluntary Professor, UnB Faculty of Medicine; Coordinator of the Ambulatory Psoriasis Center, Brasilia Hospital Universitário



As part of its continued studies of psoriasis, this second part of the Continuing Medical Education in Dermatology segment of the Anais Brasileiros de Dermatologia introduces biological immunomodulators. Also known as "biologics", these drugs act on the immunopathogenetic steps of psoriasis by changing its features and progression. This paper also reviews some of the immunologic aspects of psoriasis.

Key-words: psoriasis; psoriasis/ immunology; psoriasis/therapy.


Psoriasis is an inflammatory, chronic and recurrent disease mainly affecting the skin and joints. In histology, it presents with cellular hyperproliferation. Onset and disease course depend on genetic, behavioral and environmental factors.1-5

Despite showing benign progression, psoriasis has a big impact on the quality of the patient's life (QL). It interferes with daily activities, social relations and even has psychosocial aspects.6-8

The Psoriasis Area and Severity Index (PASI) is used to assess the severity of the disease, which may vary from 0 to 72. An index above 18 means the disease is severe. PASI reference 75 signifies a 75% reduction of the pre-treatment index and is used to evaluate therapeutic success. When a 50% increase of this index appears after a period of improvement, the disease is considered recurrent.5 PASI does not take account of the drug's impact on QL, which in daily clinical practice is important for choosing treatment.6

Most dermatologists have a hard time managing severe and extensive conditions of psoriasis7. With the options available at the present time, variable and often frustrating results are obtained apart from the undesirable and frequent side effects.10

Since 1954, severe cases of psoriasis have been treated with psoralen and ultraviolet A radiation (PUVA). In 1971, methotrexate (MTX) was approved by the Food and Drug Administration (FDA) for treating severe cases, even prior to being approved for rheumatoid arthritis.7 Etretinate, the first oral retinoid, was only introduced 15 years ago in 1986.10

Cyclosporine was only approved by the FDA in 1998 after obtaining excellent results from treating rheumatoid arthritis and Crohn's disease.8 Still, this drug did not achieve widespread acceptance among dermatologists, probably due to its nephrotoxicity, high recurrence rate and usage restrictions. 10 By contrast, in well-selected patients, cyclosporine remains an excellent choice for short-term regimens. Its quick-response and the possibility of using it in combinational or rotational regimens are worth noting.

With advances in elucidating the etiopathogenic mechanisms of psoriasis, mainly after beginning cyclosporine use, immunological alterations of the disease are currently being studied. Cellular hyperproliferation, which used to be taken as the cause of the disease, is now understood to be a consequence of the inflammatory process and mediated by T cells.13,14

Based on these etiopathogenic mechanisms and with the experience acquired from managing other immunological diseases in rheumatology and gastroenterology, clinical trials were begun with a novel class of medication, namely biologic response modifying agents, or simply biologics.12,15


Biologics are a class of agents defined by the FDA as "derived from living matter (human, vegetal, animal or microorganisms) used in the treatment, prevention and cure of diseases in humans."10

Biologic therapies include: a) prepared biologics, like blood and vaccine derivatives; b) recombinant peptides or proteins, like growth hormone and erythropoietin; c) antibody therapy; d) therapies with nucleic acids and e) genetic and cellular therapies.16

This class of medication, dealt with in this CME study, is represented by proteic drugs systemically inducing phenotypic alterations in immune response against psoriasis.10

Chart 1 lists the systemic drugs for use with psoriasis which have already been approved by the FDA, as well as some that are being developed.10

To understand the mechanism of action of a few of these agents, the immulogical aspects of psoriasis that are currently known will be presented.


The histological examination of the plaque psoriasis shows alterations like thickening of the epidermis, parakeratosis, lymphocytic inflammatory infiltrate and vasodilatation. Until the 1990s, due especially to its proliferative characteristics, the disease was thought to stem from keratinocytes and that the inflammation was a secondary event. More recently, however, it was shown that these proliferative alterations were in fact triggered by a series of inflammatory phenomena mediated by T lymphocytes.17

The evidence backing up this theory is of a laboratorial and clinical nature. The first clues of immunological participation in psoriasis arose with psoriasis patients who had received organ transplants. To prevent a transplant rejection these patients were given cyclosporine, an immunosuppressor agent and inhibitor of the proliferation and activity of T cells. The cutaneous manifestations of their psoriasis showed significant improvement. This fact led to the suggestion that T cells were actually involved in precipitating and maintaining the disease.18,19

Later in laboratory experiments, an animal model with immunodeficiency was injected with active T cells from a psoriatic lesion. Consequently, as the skin was prone to infection, the disease was induced.13,20,21

Clinical trials with denileukin difitox, a toxin used against activated T lymphocytes, also led to improvement of the psoriatic lesions.13

T cells are believed to consist of a high level of specificity and are mediated by a receptor. In the immune system, specific T cells probably act in a set place and time.

For this specific action of T cells to occur, various sequential steps are required, which are related amongst themselves. They are shown below (Chart 2):

Chart 2 - Click to enlarge

a) Activation of T cells

This occurs due to a series of stimuli beginning on the peripheral tissue in response to an injury. The stimuli induce an activation of dendritic cells, namely the antigen presenter cells (APC) migrating to the lymph nodes to join up with native T cells. This connection occurs due to the mediation of antigen in association with the leukocyte function type 1 (LFA-1) and CD2, present in T cells and intercellular adhesion molecule 1 (ICAM-1) and LFA-3, present in APC.13,22

LFA-1 belongs to the beta-2-integrin family of adhesion molecules, characterized by heterodimers with a common beta chain (CD 18) and one alpha chain (CD11a).

The APC are able to active the specific T-cell group for a determined internalized antigen. For this to occur, it is necessary for an interaction to occur among specific pairs of receptors and ligands, something which Kupper calls immune synapses, on the interface of the two cells. Accordingly, the T-cell receptors recognize the antigenic peptides anchored to the major histocompatibility molecules (HMC), class I or II.14,22

In these synapses, co-stimulation occurs, represented by intercellular interaction without any antigenic specificity, when the CD28 cells cross-link the CD80 and CD86, and T cell LFA I binds with ICAM-1. If co-stimulation does not occur, it may induce T-cell apoptosis or lead to anergy (Figure 1).22

b) Migration of T cells to the skin

Once activated, T cells are divided and multiply. They end up playing a role of memory effector T cells. This memory trait respects anatomical localization. The cells activated by the skin's original stimuli express the cutaneous lymphocyte antigen (CLA), i.e. the receptors for chemokines CC 4 and 10, and LFA-1.22 These cells interact progressively and preferentially with skin vessels expressing E-selectin, P-selectin, and linked to chemokines and ICAM-1. If there is interaction between the antigens expressed in T cells and in the endothelium, the cells experience diapedesis. This is how they manage to reach the skin where they can act like effectors. In the absence of stimuli, they return to the lymph node.13,14,22

a) Effector Function

If there is a pathological release of cytokines, like TNF-alpha, there is increased expression of endothelial E-selectin and ICAM-1 of skin memory T cells, where they act effectively to fight against aggressor stimuli. These T cells release cytokines that act in association with other cytokines produced by other local cellular types, like macrophages, dendritic cells, endothelial cells and keratinocytes.13

Psoriasis prompts a "subversion" of this elegant system.22 The immune system identifies psoriatic auto-antigens as foreign. The keratinocytes, dendritic cells and macrophages of the skin release TNF-alpha. The T lymphocytes reactive to psoriatic auto-antigens are activated and mediated by LFA-1. These T, CD4 and CD8 cells also release cytokines, like TNF-alpha and interferon-gamma, and with the other cytokines secreted by other epidermal cells, allow the process to be perpetuated.7 Accordingly, in psoriasis there is predominant action from Th1 T cell types.

Chart 2 summarizes the process.


Once a few aspects of the immunological mechanism of psoriasis were reviewed, strategies could be established. The following steps describe how to orient biologic agents to control the disease.13,23,24 (Figure 1).

a) Elimination or reduction of the number of pathogenic T cells

Given that psoriasis is a T-cell mediated disease, when using a given drug or toxin that induces the cellular death of a determined pathogenic T-cell group, the clinical condition is bound to improve. This is made possible when the cellular type is marked, and when, under the effect of natural killer cells (NK) and macrophages, this mark leads to apoptosis.

Alefacept is a drug that has this mechanism of action. The medication is a human LFA-3 fusion protein with pork Fc immunoglobulin G (IgG1). It binds to the CD2 region of the circulating effector memory T cell, and induces apoptosis.14,21

b) Preventing intercellular interactions

Preventing cell-to-cell interactions may inhibit cellular activation or T-cell migration to the skin. In both situations, it interferes with the pathogenic mechanisms of psoriasis.13,17

Efalizumab is a humanized anti-CD11a monoclonal antibody. Each body binds with to the LFA-1 (CD11a) alpha chain and blocks its interaction with ICAM-1. As such, it prevents the activation and migration of T cells.22

c) Immune deviation

In psoriatic patients, a phenotypic predominance of T cell type 1 is observed with its respective pro-inflammatory cytokines, which include TNF-alpha, INF-gamma and interleukin Il-2, IL-12, IL-8. The use of proteins naturally occurring in the organism may lead to a modification of this T1 cell pattern. It has been noted that T cell type 2 cytokines, like IL-4, IL-10 and IL-11, in physiological or greater doses, may inhibit the proliferation of T cell type 1 and, consequently, cytokine production.13,17

With the inversion of predominant cytokines, the immune system undergoes modification and interrupts the mechanism by which the psoriasis is maintained.

The results of the clinical essays were good, though inferior to those obtained with other biologic agents. Better results might occur with synergy between these T-cell type 2 cytokines and anti-IL-12 antibodies.13

d) Inactivation of cytokines

Cytokines, if already produced, may be blocked prior to acting on the pathogenesis of the psoriasis. They have managed to be blocked with the use of monoclonal antibodies and protein fusion particles.13,14,17

Among the cytokines involved in psoriasis, TNF-alpha stands out due to its direct participation at the very outset of the immune response and to its effects on keratinocytes, which stimulate their hyperproliferation through the action of epidermal growth factor (EGF). TNF-alpha is also noteworthy due to its participation on the endothelium, where it increases molecular adhesion and vascular endothelium growth factor (VEFG).27

Etanercept, infliximab and adalimumab are drugs that work toward preventing the action of TNF-alpha.23

Infliximab and adalimumab are anti-TNF-alpha monoclonal antibodies. Etanercept is a TNF-alpha Ig-receptor fusion protein.28


To synthesize drugs that act on psoriasis, a few safeguards must be taken.13

- The binding of these agents must be specific

For this to happen, the following strategies may be employed.

The de novo in-laboratory synthesis of proteins that occur naturally, the ligands. They may be receptors or cellular surface markers (hence, the "cept" derivation in the nomenclature of biologic agents).

The synthesis of monoclonal antibodies in laboratory animals (mab).29 In relation to mab terminology, the following suffixes exist and are utilized in the nomenclature of biological medications: umab: human monoclonal antibody; zumab: humanized monoclonal antibody; ximab: chimeric monoclonal antibody.

- The bind must be enough for the desired effect, which must be long-lasting

The formed molecule-a ligand or antibody-must be maintained in circulation or in the tissues so that repeated doses of medication are not necessary.

This synthesized protein is coupled to a human immunoglobulin, in general IgG1, which is thus not eliminated by the reticuloendothelial system. It keeps circulating and acting on the tissues for a longer period of time.13

- The agents must be immunologically silent

It is important for these agents to not stimulate the immune system so as to not allow toxicity symptoms to develop or trigger the formation of neutralizing antibodies against themselves.


When fusion proteins are between ligands and humans, the immunological system does not identify them as foreign. Synthesized monoclonal antibodies in animals, especially in mice, must be humanized, i.e. anchored to murine type proteins, to curb immunological reactions.

ALEFACEPT (Amevive®)

This agent inhibits the activation and proliferation of T cells by binding CD2 molecule of these cells and preventing their interaction with LFA-3. It also stimulates the expression of active NK cell receptors and macrophages, leading to T-cell apoptosis with high levels of CD2, which are the activated memory cells. This peculiarity ensures the specificity of its action. It saves native T cells so that the number of T cells in the skin is greater than in circulation.

The use of alefacept has been approved by the FDA to be administered either intravenously (IV), in doses of 7.5 mg per week, or intramuscularly (IM), 15 mg weekly. A randomized, double-blind, placebo-controlled study was performed on 533 patients, utilizing the 7.5 mg weekly dose, IV in two 12 week cycles, separated by a 12 week interval. They were divided into three groups, with the first one receiving two cycles of alefacept; the second, one cycle of alefacept and a placebo cycle; and the third, a placebo cycle and an alefacept cycle. In both cycles, PASI fell in patients who received alefacept for 12 weeks and continued falling after the last dose. In the first cycle, the maximum reduction of the original PASI was 47% in groups with alefacept and 20% in placebo groups. The group receiving the second cycle of alefacept has an additional benefit of a 54% drop in the original PASI in the sixth week of post-treatment.32-35

The lymphocyte count must be monitored during the entire treatment. The best results were seen to occur in patients experiencing a reduction in basal lymphocyte count which was greater or equal to 25%. This reduction takes place within the first six weeks of treatment. The cell count must be made every two weeks from the beginning of treatment.34

Administering the drug is well tolerated by IM as well as IV. Reported adverse effects, such as shivering, colds and sore throat, and reactions at the IM injection site were lesser during the second cycle than the first. When the lymphocyte count falls below 250 cells/ mL opportunistic infections are described, though they are mild and responsive to conventional therapy.34


This drug is a murinic, humanized monoclonal antibody utilized against CD11a, namely subunit alpha of LFA-1. It prevents this chain and thereby avoids activating T cells and their migration to the skin and adhesion to keratinocytes.

It is administered subcutaneously (SC) in a 1-to-2 mg/kg dose on a weekly basis for 12 weeks. Following a 12-week interval, a new cycle may be started.37 Clinical studies are in progress to determine further effects of continuous SC use. They have shown good results thus far.37,38

Acute side effects are cephalea, shivering, fever, nausea, vomiting and myalgia. Side effects occur within the first two days of administering the drug and tend to regress during treatment. In addition to these, other mild-intensity infectious conditions have been described, like asthenia and exacerbation of the psoriasis. In some cases, a "rebound effect" was reported after withdrawing the drug at the end of the first 12 weeks. This is similar to what occurred with cyclosporine. 38,39

Randomized, double-blind, placebo-controlled phase III clinical studies with 1-to-2 mg/kg daily doses for 12 weeks demonstrated a 75% improvement of the original PASI in 27.6% and 29.2% of patients, respectively, compared to 3.4% for the placebo group. A 50% improvement of the original PASI occurs in 55.6% and 54.5% of patients, respectively.37,40


Etanercept is a recombinant TNF-alpha receptor protein binding the FC fraction of human immunoglobulin G1 (IgG1). Despite carrying this faction, etanercept does not in vitro induce complement-mediated cellular lysis. The drug works analogically to one naturally occurring in the organism. It competitively prevents TNF-alpha from binding to the receptors of the cell surface, when anchored to this cytokine.41,42 In addition, it presents with low antigenicity. 43,44

It is administered SC in a 25 mg dose twice weekly.43

Etanercept was approved by the FDA for rheumatoid arthritis (RA) and psoriatic arthritis (PA). It is observed in PA patients, showing good clinical improvement on the cutaneous psoriasis lesions. This is the reason for which studies have been undertaken on its use with plaque psoriasis.42,44,45

The association with etanercept and MTX in rheumatoid arthritis has been studied. In a randomized, double-blind, placebo-controlled study, the isolated use of etanercept and MTX was compared with treatments using the two drugs in tandem. The results obtained show that the combination of the two drugs significantly reduced the disease's activation, in addition to producing a functional recovery of the joint and delaying radiological progression of the process.46 Etanercept can also be used in association with PUVA.

In clinical trials, the side effects described are scarce when compared to the placebo group. Reactions at the injection site, like erythema, pruritus, pain and edema, were the most cited. Mild infections might also occur, which at times require hospitalization.46 Thus far, there has been no observed increase in the incidence of malignant neoplasias.47

INFLIXIMAB (Remicade®)

Infliximab, like etanercept, is a drug that prevents the action of TNF-alpha. However it is an anti-TNF-alpha chimeric monoclonal humanized antibody. Circulating TNF-alpha, anchored to the antibody, neither binds to its receptor nor activates it. The drug might connect with the TNF-alpha already coupled to its receptor. This leads to inverting the process of controlling psoriasis. In addition, this antibody participates in the complement-mediated lysis of the cells expressing the TNF-alpha on their surface.48

For the time being, this drug is authorized by the FDA for treating Crohn's disease (CD) and RA. Controlled, multicenter clinical trials on psoriasis and psoriatic arthritis are under way. Reports do exist that show increased effectiveness on plaque psoriasis when in combination with UVB phototherapy.49-53

It is administered by slow IV in periods of two-to-three hours of infusion, in a 5 mg/kg dose for CD and 3 mg/kg for RA. After the first infusion, new doses are repeated every two-to-six weeks, and afterward every eight weeks. The best results for use on psoriasis are obtained with a 10 mg/kg dose, by respecting the same intervals.48,54,55

The medication is tolerated well. The most common side effects are related to infusion and include dyspnea, urticaria, hypotension, rubor and cephalea. These events can occur up to two hours after the infusion and must be monitored in a hospital environment. A few reports exist on the occurrence of a syndrome similar to lupus, at which time the treatment must be suspended. Patients with mild congestive cardiac insufficiency must be followed up. In the event the condition worsens, medication must also be interrupted.48,56

It is counter-indicated in patients with moderate to severe congestive cardiac insufficiency and for those in the midst of an active infection.48

Some care must be taken when indicating treatment with immunomodulator drugs. Thus, prior to starting treatment, patients must be sorted out for tuberculosis, hepatitis, HIV, metabolic profile and complete hemogram. During treatment, immunization with a living virus is prohibited.49,57


The use of biologics represents a novel therapeutic approach in dermatology. It has been used for a few years in other specialties, like rheumatology. Dermatologists must nonetheless be vigilant regarding the toxicity of biologics, whether it be renal, hepatic or on the bone marrow, in addition to immunosuppression, teratogenicity and carcinogenesis.

Clinical essays with biologic agents indicate a net improvement of the clinical condition of psoriasis, referred to as PASI 75, to the effect of 40% to 60%.32,33,34,35,37,40 Since psoriasis is a chronic disease and the medications for treating it are expensive, in Brazil biologics will most likely be used in combination, topical or systemic therapies. As such, the traditional medications, like methotrexate (MTX), cyclosporine, retinoids and phototherapy, will probably keep being used.57 In this situation, the effects of each drug will have been potentialized, and their toxic effects and the cost of treatment reduced. Nonetheless, the toxic effects of the traditional drugs-which are well known-must be recalled when performing a combination with biologics. It is also known that they are not nephrotoxic or hepatotoxic and that they seem to be useful in associations with MTX or cyclosporine.57

Another aspect to be considered is increased immunosuppression when in combination with traditional drugs, like with azathioprine, hydroxyurea and mycophenolate mofetil.57,58,59 In current studies, biologics have less impact on immunosuppression compared to traditional drugs, because they act in accordance with specific steps of the immune process. Still, the carcinogenic potential must considered mainly with prolonged use, or in patients with an increased risk of cutaneous neoplasia, like in those who have already been using phototherapy for a long time.56

In rheumatology, infliximab is used in association with MTX in an attempt to prevent the formation of anti-chimeric antibodies. There were no reports of increased carcinogenesis with this association or with etanercept and MTX.60 More studies are required, though, as is more time for these drugs to obtain definitive conclusions.

Apart from these associations, sequential therapy must be considered as well. From this perspective, two biologic agents being studies, efalizumab and infliximab, seem to act quickly. They are the drugs of choice for treating psoriasis.60,61 On the other hand, etanercept has proved to keep its effects for up to six months after the end of therapy. Alefacept also induces periods of greater remission and better efficacy in subsequent therapeutic cycles. Therefore, it seems as though they will be useful in a second phase of sequential therapy.57,62,63

As happened with rheumatology, there is little doubt that the use of biologics may come to represent a gain in the quality of the life of psoriasis patients, with less side effects or, at least, with more easily avoidable side effects.

Another important aspect to consider is the cost of treatment. In the United States of America and Europe, these medications are subsidized by insurance firms or governments. Treatment with products like etanercept and infliximab is already available on the market at a cost ranging from US$ 12,000 to US$ 20,000 annually per patient. This fact makes biologics one of the most expensive medications for developing countries like Brazil. Yet it is necessary to elaborate treatment strategies for different use options, like association or rotational therapies.56

This is why in upcoming years, more complete comparative and long-lasting studies must be performed in order to upgrade the best indication for this new class of medications in dermatology. Biologics currently represent a new hope for managing psoriasis. The risk of reactivating tuberculosis and its high cost must be observed seriously with special attention given to its possible side effects. Were the drug to be confirmed in new studies, dermatologists might find themselves faced with an opportunity to experience a novel step in therapy. Indeed, this step might be as important as the introduction of corticosteroids was in its time-or more. It is important and necessary for dermatologists to upgrade their knowledge for this new era, whose signs can already be glimpsed. This is how dermatologists will ensure their place in further research and not be left on the side-lines from other medical and scientific specialties.


Received on April 16, 2004

Approved by the Editorial Council and accepted for publication on July 05, 2004.

Questions and Answers to Questions

1. A psoríase é uma doença:

a) inflamatória;.

b) hiperproliferativa;

c) a e b estão corretas;

d) nenhuma das anteriores

2. O tratamento de casos graves de psoríase pode ser feito com os seguintes medicamentos, exceto

a. methotrexato;

b. antiinflamatórios não hormonais;

c. acitretina;

d. ciclosporina A.

3. Os biológicos são

a. derivados de material vivo usados no tratamento, prevenção e cura de doenças em humanos;

b. compostos utilizados para pesquisa de agentes etiológicos de doenças infecciosas;

c. o material resultante do metabolismo de fungos;

d. animais de laboratório.

4. Imunologicamente, a psoríase é uma doença

a. que cursa com hipercomplementenemia;

b. que representa reação do tipo I, de Gell-Coombs;

c. do mesmo grupo do lúpus eritematoso sistêmico;

d. mediada por células T.

5. São indícios da característica imunológica da psoríase, exceto

a. melhora clínica dos pacientes psoriásicos após o uso de tratamento imunossupressor para transplante de órgãos;

b. resultados após o uso de ciclosporina A;

c. melhora com retinóides;

d. indução de psoríase em modelos experimentais.

6. TNF-a

a. só é sintetizado pelos linfócitos;

b. está envolvido na ativação de linfócitos T;

c. auxilia apenas a indução da psoríase;

d. induz a apoptose das células apresentadoras de antígeno.

7. Pasi 75 representa

a. redução de 75% do Pasi inicial após tratamento;

b. recidiva de 75% da psoríase após um período de melhora;

c. um padrão para avaliar a resposta à terapêutica;

d. a e c corretas.

8. Considera-se recidiva da psoríase

a. aumento em 50% no Pasi após um período de melhora;

b. aumento em 75% no Pasi após um período de melhora;

c. piora acentuada da doença após interrupção do tratamento;

d. qualquer piora do quadro em vigência de tratamento.

9. A ação das células T na psoríase

a. se faz por etapas caracterizadas por ativação das células T, sua migração para a pele e função efetora das células T;

b. está ligada às céllulas apresentadoras de antígenos;

c. está relacionada a citocinas produzidas pelas células Th1;

d. todas respostas estão corretas.

10. As citocinas relacionadas ao desencadeamento da psoríase

a. são as citocinas produzidas pela células Th1;

b. são as citocinas produzidas pelas células Th2;

c. são citocinas pró-inflamatórias;

d. a e c são corretas.

11. As principais citocinas relacionadas ao desencadeamento da psoríase são

a. TNF-a;

b. INF-g;

c. IL-8; IL-12; IL-1; IL-6;

d. todas as anteriores.

12. A ação das células T existe graças às seguintes ligações entre elas e as células apresentadoras de antígenos

a. LFA-1 e ICAM-1;

b. CD2 e LFA-3;

c. CD28 e CD80 e CD86;

d. todas as anteriores.

13. A ação dos biológicos na psoríase se faz

a. por meio de ligação a qualquer tipo de célula;

b. por meio de ligação a receptores de células Th2;

c. por meio de ação anti TNF-a;

d. não há necessidade de qualquer ligação.

14. Os biológicos já aprovados pelo FDA para tratamento da psoríase são

a. alefacept;

b. efalizumab;

c. a e b;

d. infliximab.

15. Os efeitos colaterais dos biológicos são

a. leves, pouco intensos e bem controlados;

b. graves, muito intensos, mas muito bem controlados;

c. relacionados a uma imunossupressão grave;

d. nunca ocorrem se os pacientes forem bem monitorados.

16. Os biológicos são drogas que devem ser administradas

a. SC, IM ou EV;

b. via oral;

c. só IM;

d. todas essas vias são possíveis.

17. A dosagem dos biológicos

a. é a mesma para todos os produtos;

b. varia de acordo com o produto utilizado;

c. ainda não está estabelecida;

d. nenhuma dessas resposta é correta.

18. A terapia de combinação dos biológicos com outras drogas clássicas para psoríase

a. já é uma modalidade de tratamento recomendada;

b. ainda não está sendo realizada;

c. já está sendo realizada, mas ainda necessita de estudos mais longos;

d. provavelmente nunca será realizada devido aos efeitos tóxicos das combinações.

19. O custo dos produtos biológicos

a. é baixo;

b. não representa um problema nessa modalidade de tratamento;

c. é alto e deve ser levado em consideração na instituição do tratamento;

d. é o menos importante frente aos grandes benefícios obtidos com o tratamento.

20. A terapia com os biológicos

a. é uma nova modalidade de terapia com que os dermatologistas devem começar a se familiarizar;

b. é muito antiga e não foi levada em consideração pela dermatologia;

c. é uma modalidade de tratamento que não é promissora pelos altos custos envolvidos;

d. a e c corretas.


Tratamento sistêmico da psoríase - Parte I: metotrexato e acitretina

2004; 79(3): 263-278

1 - b

11 - b

2 - b

12 - e

3 - b

13 - c

4 - b

14 - d

5 - c

15 - a

6 - d

16 - d

7 - b

17 - b

8 - c

18 - e

9 - c

19 - a

10 - c

20 - c

  • 1. Arruda LHF, Campbell GAM, Takahashi MD. Psoríase. An bras Dermatol 2001; 76(2):141-67.
  • 2. Lebwohl M. Psoriasis. Lancet 2003; 361:1197-204.
  • 3. Ortonne JP. Recent developments in the understanding of the pathogenesis of psoriasis. Br J Dermatol 1999; 140(suppl. 54):1-7.
  • 4. Camp RDR. Updates from the Third International Congresso n Psoriasis: from gene to clinic, the Royal College of Physicians, London, UK, 21-23 November 2002. Br J Dermatol 2003; 148:878-84.
  • 5. Kirby B e Griffiths CEM. Psoriasis: the future. Br J Dermatol 2001; 144(suppl 58):37-43.
  • 6. Krueger GG, Feldman SR, Camisa C, Duvic M, Elder JT, Gottlieb AB et al Two considerations for patients with psoriasis and their clinicians: What defines mild, moderate and severe psoriasis? What constitutes a clinically significant improvement when treating psosriasis? J Am Acad Dermatol 2000; 43:281-5.
  • 7. Mackay IR e Rosen FS. Advances in immunology. N Engl J Med 2001; 345(5):340-50.
  • 8. Arruda LHF, Moraes APF. The impact of psoriais on quality of life. Br J Dermatol 2001;144(suppl 58):33-36.
  • 9. Frederiksson T e Pettersson V. Dermatológica 1978; 157:238-44.
  • 10. Menter MA, Krueger GC, Feldman SR e Weinstein GD. Psoriasis treatment 2003 at the new millennium: Position paper on behalf of the authors. J Am Acad Dermatol 2003; 49(2suppl):S39-S43
  • 11. Olsen EA. The pharmacology of methotrexate J Am Acad Dermatol 1991;25:306-18.
  • 12. Najarian DJ e Gottlieb AB. Conections between psoriasis and Crohn's disease. J Am Acad Dermatol 2003; 48:805-21.
  • 13. Mehlis SL, Gordon KB. The immunology of psoriasis and biologic immunotherapy. J Am Acad Dermatol 2003; 49(2supp.):S44-S50.
  • 14. Krueger JG. The immunologic basis for the treatment of psoriasis with new biologic agents. J Am Acad Dermatol. 2002; 46:1-23.
  • 15. Deventer SJH. Anti-tumour necrosis factor therapy in Crohn's disease: where are we now? Gut 2002; 51:362-3.
  • 16. Sandborn WJ e Targan SR. Biologic therapy of inflammatory bowel disease. Gastroenterology 2002; 122:1592-608.
  • 17. Gordon KB e McCormick TS. Evolution of biologic therapies for the treatment of psoriasis. SKINmed 2003; 2(5):286-94.
  • 18. Robert C e Kupper TS. Inflammatory skin diseases, T cells, and immune surveillance. N Engl J Med 1999; 341(24):1817-28.
  • 19. Gottlieb AB, Krueger JG, Witkowski K, Dedrick R, Walicke PA e Garovoy M. Psoriasis as a model for T-cell-mediated disease - immunobiologic and clinical effects of treatment with multiple doses of Efalizumab, an anti-CD11a antibody. Arch Dermatol 2002; 138:591-600.
  • 20. Nickoloff BJ, Kunkel SL, Burdick M e Strieter RM. Severe combined immunodeficiency mouse and human psoriatic skin chimeras - validation of a new animal model. Am J Pathol 1995; 146(3):580-8.
  • 21. Nickoloff BJ, Wrone-Smith T, Bonish B, Porcelli SA. Response of murine and normal human skin injection of allogenic blood-derived psoriatic immunocytes . Arch Dermatol 1999; 135:54-52.
  • 22. Kupper TS. Immunologic Targets in Psoriasis. N Engl J Med 2003; 349(21):1987-90.
  • 23. Griffiths CEM. Immunotherapy for psoriasis: from serendipty to selectivity. Lancet 2002; 359:279-80.
  • 24. Kirby B e Griffiths CEM. Novel immune-based therapies for psoriasis. Br J Dermatol 2002; 146:546-51.
  • 25. Naldi L. Alefacept for psoriasis: promising drug, open questions. Arch Dermatol 2002; 138:1238-40.
  • 26. Lebwohl M, Tyring SK, Hamilton TK, Toth D, Glazer S, Tawfik NH et al A novel targeted T-cell modulator, Efalizumab, for plaque psoriasis. N Engl J Med 2003; 349:2004-13.
  • 27. Leonardi CL, Powers JL, Matheson RT, Goffe BS, Zitnik R, Wang A et al Etanercept as motherapy in patients with psoriasis. N Engl J Med 2003; 349:2014-22.
  • 28. Gottlieb AB, Masud S, Ramamurthi R, Abdulghani A, Romano P, Chaudhari U et al Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-a monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris. J Am Acad Dermatol 2003; 48:68-75.
  • 29. Mehrabi D, DiCarlo JB, Soon SL, McCall CO. Advances in the management of psoriasis: monoclonal antibody therapies. Int J Dermatol 2002; 41:827-35.
  • 30. Barland C. Addition of low-dose methtrexate to infliximab in the treatment of a patient with severe, recalcitrant pustular psoriasis. Arch Dermatol 2003; 139:949-50.
  • 31. Ellis CN, Krueger GG. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001; 345:248-55.
  • 32. Lebwohl M, Christophers E, Langley R, Ortonne JP, Roberts J and Griffiths CEM. An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol 2003; 139:719-27.
  • 33. Krueger GG, Papp KA, Stough DB, Loven KH, Gulliver WP, Ellis, CN. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 couses of alefacept in patients with chronic plaque psoriasis. J Am Acad Dermatol 2002; 47:821-33.
  • 34. Finlay AY, Salek MS and Haney J. Intramuscular alefacept improves health-related quality of life in patients with chronic plaque psoriasis. Dermatology 2003; 206:307-15.
  • 35. Lowe NJ, Gonzalez J, Bagel J, Caro I, Ellis CN and Menter A. Repeat courses of intravenous alefacept in patients with chronic plaque psoriasis provide consistent safety and efficacy. Int J Dermatol 2003; 42:224-30.
  • 36. Krueger GG and Callis KP. Development and use of alefacept to treat psoriasis. J Am Acad Dermatol 2003; 49:S87-97.
  • 37. Leonardi CL. Efalizumab: an overview. J Am Acad Dermatol 2003; 49:S98-104.
  • 38. Granstein RD. New treatments for psoriasis. N Engl J Dermatol 2001; 345:284-7.
  • 39. Tutrone WD, Kagen MH, Barbagallo J, Weinberg JM. Biologic therapy for psoriasis: a brief history, II. Cutis 2001; 68:367-72.
  • 40. Gordon KB, Papp KA, Hamilton TK et al Efalizumab for patients with moderate to severe plaque psoriasis. A randomized controlled trial. JAMA 2003; 290:3073-80.
  • 41. Mease PJ. Etanercept, a TNF antagonist for treatment of psoriatic arthritis and psoriasis. Skin Therapy Letter 2003; 8(1):1-4.
  • 42. Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ et al Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med 2000; 342:763-9.
  • 43. Goffe B, Cather JC. Etanercept: an overview. J Am Acad Dermatol 2003; 49:S105-11.
  • 44. Culy CR, Keating GM. Etanercept: an updated review of its use in rheumatoid arthritis, psoriatic arthritis and juvenile rheumatoid arthritis. Drugs 2002; 62(17):2493-537.
  • 45. Kurschat P, Rubbert A, Poswig A, Scharffetter-Kochanek K, Krieg T, Hunzelmann N. Treatment of psoriatic arthritis with etanercept. J Am Acad Dermatol 2001; 44:1052.
  • 46. Heidje LKD, Jager JP, Gough A et al Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomized contolled trial. Lancet 2004; 363:675-81.
  • 47. Mease PJ, Goffe BS, Metz J, VanderStoep A, Finck B, Burge DJ. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomized trial. Lancet 2000; 356:385-90.
  • 48. Gottlieb AB. Infliximab for psoriasis. J Am Acad Dermatol 2003; 49:S112-7.
  • 49. Victor FC, Gottlieb AB. TNF-alpha and apoptosis: implications for the pathogenesis and treatment of psoriasis. J Drug Dermatol 2002; 3:264-75.
  • 50. Oh CJ, Das KM, Gottlieb AB. Treatment with anti-tumor necrosis factor a (TNF-a) monoclonal antibody dramatically decreases the clinical activity of psoriasis lesions. J Am Acad Dermatol 2000; 42:829-30.
  • 51. Labarca C, Massardo L, Garcia PI, Jacobelli S. Evaluación del tratamiento con infliximab em enfermos con artritis inflamatoria refractaria a drogas habituales. Ver Méd Chile 2003; 131:1157-64.
  • 52. Newland MR, Weinstein A, Kerdel F. Rapid response to infliximab in severe pustular psoriasis, von Zumbusch type. Int J Dermatol 2002; 41:449-52.
  • 53. Al-Salem IH. Striking and rapid improvement of plaque psoriasis with infliximab - a report of two cases. Dermatology 2003; 207:54-6.
  • 54. Weinberg JM, Saini R. Biologic therapy for psoriasis: the tumor necrosis factor inhibitors - infliximab and etanercept. Cutis 2003; 71:25-9.
  • 55. Schopf RE, Aust H, Knop J. Treatment of psoriasis with the chimeric monoclonal antibody against tumor necrosis factor a, infliximab. J Am Acad Dermatol 2002; 46:886-91.
  • 56. Chaudhari U, Mulcahy LD, Dooley LT, Baker DG, Gottlieb AB. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomized trial. Lancet 2001; 357:1842-7.
  • 57. Lebwohl M. Combining the new biologic agents with our current psoriasis armamentarium. J Am Acad Dermatol 2003; 49:S118-24.
  • 58. Kamarashev J, Lor P, Forste A, Heinzerling L, Burg G, Nestle FO. Generalized pustular psoriasis induced by cyclosporine A withdrawal responding to the tumor necrosis factor alpha inhibitor etanercept. Dermatology 2002; 205:213-6.
  • 59. Liberopoulos EM, Drosos AA, Elisaf MS. Exacerbation of tuberculosis enteritis after treatment with infliximab. JAMA 2002; 113:615.
  • 60. Weinberg JM, Tutrone WD. Biologic therapy for psoriasis: the T-cell-target therapies - efalizumab and alefacept. Cutis 2003; 71:41-5.
  • 61. Gottlieb AB, Chaudhari U, Mulcahy LD, Li S, Dooley LT, Baker DG. Infliximab monotherapy provides rapid and sustained benefit for plaque-type psoriasis. J Am Acad Dermatol 2003; 48:829-35.
  • 62. Davison SC, Bunker CB, Basarab T. Etanercept for severe psoriasis and psoriatic arthritis: observation on combination therapy. Br J Dermatol 2002; 147:831-2.
  • 63. Leone G, Rolston K. Alefacept for chronic plaque psoriasis: a selective therapy with long-lasting disease remissions and an encouraging safety profile. Dermatol Nurs 2003; 15(3):216-26.

  • Correspondence
    Lúcia Arruda
    Av. John Boyd Dunlop, S/N - Jardim Ipaussurama
    13059-900 Campinas SP
  • *
    Work done at "Hospital Celso Pierro, Pontifícia Universidade Católica de Campinas - PUC"

Publication Dates

  • Publication in this collection
    21 Sept 2004
  • Date of issue
    Aug 2004


  • Accepted
    05 July 2004
  • Received
    16 Apr 2004
Sociedade Brasileira de Dermatologia Av. Rio Branco, 39 18. and., 20090-003 Rio de Janeiro RJ, Tel./Fax: +55 21 2253-6747 - Rio de Janeiro - RJ - Brazil