Article Text

TNF-α in a molecularly targeted therapy of psoriasis and psoriatic arthritis
  1. Dominika Wcisło-Dziadecka1,
  2. Martyna Zbiciak-Nylec2,
  3. Ligia Brzezińska-Wcisło2,
  4. Urszula Mazurek3
  1. 1Department of Skin Structural Studies, Chair of Cosmetology, School of Pharmacy with Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Poland
  2. 2Chair and Department of Dermatology, School of Medicine in Katowice, Medical University of Silesia, Poland
  3. 3Chair and Department of Molecular Biology, School of Pharmacy with Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Poland
  1. Correspondence to Dr Dominika Wcisło-Dziadecka, Department of Skin Structural Studies, School of Pharmacy with Division of Laboratory Medicine, Silesian Medical University, ul. Kasztanowa 3, Sosnowiec 41-200, Poland; ddziadecka{at}


Psoriasis is a chronic immunological skin disease and patients with this disorder typically experience a significant decrease in their quality of life. The disease is traditionally managed with topical and systemic agents (retinoids, ciclosporin A, methotrexate), but these treatment options are often long-term and their effects can be inconsistent and not ideal. The use of biological drugs in dermatological treatment is relatively new and began in the early 2000s. It should be noted that, in most countries, in order for biological treatment to be administered, specific criteria must be met. The current treatment options for psoriasis and psoriatic arthritis include tumour necrosis factor alpha (TNF-α) blockers, interleukin (IL)-12 and IL-23 inhibitors, T cell inhibitors and B cell inhibitors. These classes of biological drugs are characterised by protein structure as well as high molecular weight and their effectiveness is evaluated based on the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI). TNF-α antagonists are one such class of biological drugs which includes infliximad, etanercept and adalimumab. Infliximab is a chimeric protein that is administered via intravenous infusions as a monotherapy in psoriasis vulgaris. Etanercept is indicated for use in both psoriasis vulgaris and psoriatic arthritis and it is the only drug that can be used as a treatment for children under the age of 8 with psoriasis. The drug is administered subcutaneously. Finally, adalimumab is a fully human monoclonal antibody that neutralises both free and membrane-bound TNF-α and is used in the treatment of psoriasis vulgaris and psoriatic arthritis. This article reviews the latest research in the use of TNF-α for the treatment of moderate to severe psoriasis and psoriatic arthritis. The results of research in this field are promising and confirm the effectiveness and safety of biological drugs as dermatological treatments for psoriasis. In particular, adalimumab, etanercept and infliximab are promising therapeutic options for patients with moderate to severe psoriasis and psoriatic arthritis who are unresponsive to conventional treatment strategies and they can significantly improve the quality of lives in patients with this disease.


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Psoriasis is a chronic immunological skin disease that affects both sexes mainly between the ages of 15 and 25 years. Additionally, patients may have genetic predispositions that increase their susceptibility to developing the disorder (box 1). Psoriasis is characterised by silvery inflammatory scale lesions and results in a significant decrease in patients’ quality of life.

Box 1

Epidemiology of psoriasis

  • 1. Sex:

    • Psoriasis affects both sexes

  • 2. Age:

    • Can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years

    • Onset before age 40 usually indicates a greater genetic susceptibility and a more severe or recurrent course of psoriasis

  • 3. Frequency:

    • The prevalence of psoriasis in Western populations is estimated to be around 2–3%

    • A survey conducted by the National Psoriasis Foundation (a US-based psoriasis education and advocacy group) found a prevalence of 2.1% among adult Americans. The study found that 35% of people with psoriasis could be classified as having moderate to severe psoriasis

  • 4. Genetics of psoriasis:

    • Around one-third of people with psoriasis report a family history of the disease. Studies of monozygotic twins suggest a 70% chance of a twin developing psoriasis if the other twin has it. The concordance is around 20% for dizygotic twins

    • These findings suggest both a genetic predisposition and an environmental response in developing psoriasis

The standard treatment options for psoriasis include retinoids, ciclosporin A and methotrexate, while the use of biological agents as a treatment is relatively new (table 1). In the USA and in Europe the first drugs for the treatment of psoriasis vulgaris were registered in 2003 (efalizumab, alefacept) and in 2004 (etanercept).1 The effectiveness of these biological therapies is evaluated based on Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Dermatology Life Quality Index (DLQI). In most countries the use of biological agents to treat psoriasis is permitted only when the patient meets a specific set of criteria.

Table 1

Classic therapy for psoriasis3

There are currently several groups of biological drugs available for treatment which include monoclonal antibodies, recombinant human proteins (cytokines, growth hormone, insulin, antitoxins, vaccines, blood substitutes, allergens, interferons, soluble receptors, chemokines (rh- or rhu- prefix)) and fusion proteins (drug names ending with- cept).1–3 These classes of biological drugs are characterised by their protein structure and high molecular weight. When administered as treatment options for patients, the preferred routes are intravenous, subcutaneous or intramuscular infusion while oral administration is not recommended.

During initial stages of testing, only murine monoclonal antibodies were used and, as a result, attempted clinical trials were associated with numerous complications. With the help of advances in genetic engineering, chimeric (75% human sequences, drug names ending with -ximab), humanised (95% human sequences, -zumab) and fully human antibodies (-umab) were obtained.2

The primary aim of this work is to review the recent literature on the biological treatment of psoriasis and psoriasis arthritis and to compare the effectiveness of these preparations.

Guidelines for use of biological drugs in psoriasis vulgaris

In most European countries, biological treatment of moderate to severe psoriasis vulgaris is recommended when the patient meets at least one of the following criteria:4 ,5

  1. Patients in whom effective control of treatment has not been achieved with the available systemic agents used in monotherapy or polytherapy (lack of response to treatment is defined as a PASI reduction of <50% and/or <5 DLQI points after at least 3 months of conventional systemic therapy with ciclosporin (2.5–5 mg/kg/day), methotrexate (15–30 mg/week), Psoralen Ultraviolet A (PUVA) or narrowband UVB phototherapy (no reaction or rapid deterioration during 150–200 nm PUVA session and >350 nm narrowband UVB phototherapy)).

  2. Patients in whom relapses occur rapidly (ie, within <3 months) after withdrawal of any type of treatment.

  3. Patients who require high doses of conventional systemic therapy (due to a significant risk of adverse effects related to drug toxicity).

  4. Patients who are intolerant to a systemic therapy (who experience toxicity or adverse reactions with lowest effective doses) or who have a high risk of cumulative toxicity (methotrexate, ciclosporin, retinoids, phototherapy or photochemotherapy), even when laboratory test results are normal.

  5. Patients who are not good candidates for treatment with phototherapy or photochemotherapy because of their work, daily schedule or availability.

  6. Patients with very severe unstable forms of psoriasis such as acrodermatitis continua of Hallopeau, erythroderma or generalised pustular psoriasis.

Guidelines for use of biological drugs in psoriatic arthritis

Biological therapy for psoriatic arthritis also requires certain criteria to be met. According to British guidelines, patients who qualify for treatment are as follows:

  1. Patients with ≥5 swollen joints in whom additionally elevated C-reactive protein (CRP) persisting for >3 months is observed or patients with structural joint damage due to psoriatic arthritis.

  2. Patients who did not respond to the conventional treatment methods (two drugs).

  3. Patients with severe chronic psoriasis with <3 joints involved

In these patients, treatment can be introduced when the disease is a major factor that affects their well-being and they have failed treatment with at least two conventional therapies and appropriate intra-articular treatment.

The British Association of Dermatology (BAD) guidelines for patients with psoriatic arthritis who require rapid control of their skin symptoms recommends the use of infliximab or adalimumab as the primary treatment option. Additionally, the BAD recommendations give instructions with regard to duration of treatment, which should be continued in patients with improved clinical condition after 3 months of treatment. In patients who have not responded, treatment should be continued for another 12 weeks. During this time, partial response to treatment is likely, which suggests continuing the therapy.6

Biology of tumour necrosis factor α (TNF-α)

TNF-α has emerged as a promising therapeutic target for the treatment of dermatological diseases. It is also known as cachectin, TNFSF2 (TNF superfamily member 2) and differentiation inducing factor.7 ,8 It belongs to the TNF superfamily, which is composed of over 20 proteins, and is a key pleiotropic inflammatory cytokine involved in inflammation and immune regulation.7–9

Many cell types produce TNF-α, particularly macrophages, monocytes, T and B cells, as well as synoviocytes. Keratinocytes, neurons, retinal pigment epithelial cells and glial cells also have the potential to produce TNF-α.7 ,10 ,11 The biological significance of TNF-α lies in its ability to intensify the synthesis of other cytokines, induce the apoptosis of tumour cells and stimulate the production of acute phase proteins and B cells.9

The TNF-α gene is located in the segment 6p23–6q12 of chromosome 6, within the major histocompatibility complex loci.8 Active TNF-α is a homotrimer consisting of three identical polypeptide subunits linked in an atypical way. Each of them is composed of 157 amino acid residues and has a molecular weight of 17 300 Da.7 ,10 It comes in two forms: soluble (s)TNF-α and transmembrane (tm)TNF-α.9

Currently, two types of receptors for TNF-α are distinguished: TNF-R1 (CD120a, p55/60) and TNF-R2 (CD120b, p75/80).8 These receptors differ functionally with regard to the types of transmitted signals they affect as well as structurally in their molecular weight. TNF-R1 is found in almost all cells of the human body and is stimulated by both free and transmembrane TNF-α. TNF-R2 has affinity for the transmembrane forms of TNF and can be found within the fibroblasts, endothelial cells, lymphocytes and macrophages. Additionally, TNF-α binds with two soluble receptors (sTNFR55 and sTNFR75).7–11

The activation of TNF-α receptors induces a multitude of intracellular signalling pathways. These pathways include the pro-apoptotic caspase activation pathway, NF-kappaB activation pathway, MAPK pathways (mitogen-activated protein kinase which induces transcription of genes encoding proteins involved in apoptosis, proliferation and inflammation), as well as the PKB/Akt signalling pathway (protein kinase B responsible for regulating proliferation and inflammatory response), Furthermore, TNF-α signalling activates sphingomyelinases which release second messengers.12

By binding to receptors, TNF-α activates a cascade of events within the cell and the induction of these multiple signalling pathways can either stimulate or inhibit biological processes. This multidirectional activity of TNF-α is often referred to as pleiotropy, and the final biological effect of TNF-α is dependent on which cell type it is acting on directly.

Tumour necrosis factor α antagonists

As a result of its involvement in the pathogenesis of autoimmune diseases, TNF-α has emerged as a therapeutic target for the treatment of psoriasis and rheumatoid arthritis. In recent years, studies have looked into developing inhibitors of this proinflammatory cytokine as a potential treatment for the aforementioned diseases.

According to Tracey et al, the mechanisms of action of TNF-α antagonists can be divided into two groups, one associated with the blocking of TNF receptor-mediated reactions and the other related to the direct effects of the drugs on tmTNF.13 These drugs, through TNF-α uptake, block the proinflammatory effects of this cytokine, which clinically manifests as a remission of symptoms.7

Currently, dermatological treatment of psoriasis and psoriatic arthritis is possible with three TNF-α blockers, which are discussed below. The following information is up to date and has taken into account the latest worldwide reports (figure 1).

Figure 1

Structure and clinical features of tumour necrosis factor alpha (TNF-α) inhibitors.


General information

Infliximab is a chimeric protein that is administered via intravenous infusions and, in the case of psoriasis vulgaris, it is used as a monotherapy. The drug is highly effective, and reduces skin lesions by at least 75% compared with the baseline value (PASI 75) in approximately 80% of patients treated with a dose of 5 mg/kg body weight.3 Infliximab is given at 0, 2 and 6 weeks, then every 8 weeks, and has been approved in the USA and EU for the treatment of plaque psoriasis and psoriatic arthritis.14 Some patients treated with infliximab may develop neutralising antibodies (HACA, human antichimeric antibodies) which reduce the effectiveness of the therapy. Due to the presence of murine proteins, some patients may also develop hypersensitivity reactions. These side effects typically appear within 2 h after drug infusion and therefore infliximab should only be administered in hospital.

In some patients, premedication with non-steroidal anti-inflammatory drugs, steroids and antihistamines may be required. Such treatment should especially be considered in patients for whom infliximab is administered after a break in the therapy. New psoriatic lesions that appear during infliximab treatment are often observed just before the next planned injection. In this situation it is advisable to reduce the interval between consecutive infusions from 8 to 6–7 weeks. Furthermore, it was observed that the drug efficacy during the subsequent cycle of treatment was lower than in the first one.3–5 This may be connected with the appearance of HACA. To address this, methotrexate can be included in the therapy in a weekly dose of 7.5–15 mg. If the return of treatment effectiveness is observed, methotrexate can be gradually discontinued. However, if there is no improvement, infliximab therapy should be discontinued and other therapeutic options may be tried. Testing HACA serum concentration is not recommended due to the inability to distinguish between neutralising antibodies and antibodies which are directed against infliximab but do not affect it. In the case of patients with psoriatic arthritis, from the beginning of therapy infliximab should be used along with methotrexate, except in patients who do not tolerate it.3 ,15

Scientific reports

Authors in Greece reported the following results from three patients with psoriasis vulgaris or psoriatic arthritis. The first patient had no skin lesions and the joint symptoms subsided after 7 weeks of treatment with infliximab. In the case of the second female patient with plaque and nail psoriasis as well as psoriatic arthritis, infliximab helped to control all ailments. The third case was a male patient with similar clinical manifestations who was also effectively treated with infliximab. In this study the authors draw attention to the importance of early detection of joint changes. Ultrasound may be a useful tool because it visualises synovitis and enthesitis even before the onset of clinical symptoms. If such abnormalities are detected early on in the course of psoriatic arthritis, doctors will be able to appropriately select the drug which will help to increase the effectiveness of therapy and thereby avoid disability.14

Researchers from Italy analysed the prevalence of antinuclear antibodies (ANA) in patients with psoriasis after treatment with infliximab. The researchers were interested in whether the presence of these antibodies would affect the final outcome of infliximab therapy. Serum levels of ANA, anti-ds-DNA, anti-histone, anti-nucleosome and anti-ENA antibodies were measured at baseline and after 2 and 12 months of treatment with infliximab. Serum CRP, visfatin and resistin were also assessed. The prevalence of ANA increased from 22% to 37% after 2 months and to 63% after 12 months (p<0.01) of treatment with infliximab. The prevalence of other antibodies also increased from 7% to 30% and 48% (p<0.01) for anti-ds-DNA and from 7% to 26% and 37% for anti-nucleosome antibodies (p<0.05), while the amount of anti-histone and anti-ENA antibodies remained unchanged throughout the study period. Baseline levels of resistin and CRP in the blood were higher in patients than in the control group, but their levels gradually normalised during treatment (p<0.01). In contrast, visfatin levels gradually increased (p<0.01). Taking into account the clinical symptoms of patients, it was found that ANA-positive patients with initially higher levels of resistin and CRP tended to show a faster decrease in PASI score after 2 months but, during a 1-year observation period, the PASI score did not differ between ANA-positive and ANA-negative patients. Thus, patients with ANA had a faster clinical response to infliximab therapy.16


General information

Etanercept is another drug approved for use in psoriasis vulgaris and psoriatic arthritis and it is the only drug of those described in this report that can be used in the treatment of psoriasis in children from 8 years of age. Etanercept is administered subcutaneously and the most commonly administered dose, according to medical literature, is 25 mg twice a week or 50 mg once a week.3 ,17 ,18 After 12 weeks of treatment, PASI 75 was achieved by 40% of patients. In order to increase the effectiveness of treatment, etanercept can be injected in a double dose (50 mg twice a week) in the first 3 months of therapy. The drug can be administered for no longer than 24 weeks and the effect of therapy should be visible after 12 weeks. If the treatment does not provide the expected benefits, it should be discontinued after this period. Up to 3 years of treatment with etanercept is considered safe and well tolerated by patients.19 In contrast to adalimumab, neutralizing antibodies do not develop during treatment with etanercept.3 ,19

Scientific reports

A group of American scientists compared biological drugs in terms of frequency of anti-drug antibody formation. Anti-drug antibodies occurred in 0–18.3% of etanercept-treated patients, which is rare compared with other compounds (infliximab: 5.4–43.6%, adalimumab: 8.8–44.8%, ustekinumab: 3.8–5.4%). However, the undoubted advantage of etanercept is that the presence of anti-drug antibodies is not associated with a decreased response to the treatment of psoriasis.20

The experience of doctors from Łódz´ regarding etanercept therapy in patients with psoriasis is satisfactory. Clinical improvements were observed in the majority of patients who underwent 12 weeks of treatment and the side effects were considered mild in severity. The most frequently observed side effects were reactions at the injection site such as erythema and oedema, as well as headaches, flu-like symptoms and urinary tract infections. Two patients showed more serious adverse effects in the form of optic neuritis and one patient developed thrombocytopenia (26 000/mm3).21

A randomised placebo-controlled study, which included 652 patients, found that the rate of PASI 75 after 12 weeks of treatment was achieved by 14% of those receiving 25 mg etanercept per week, 34% of patients receiving 25 mg twice weekly, 49% of patients receiving 50 mg twice weekly and 4% in the placebo group (p<0.001). After 24 weeks of treatment an improvement of 75% was also achieved by patients taking the drug in a dose of 50 mg twice a week (59%).22

Researchers from New York sought to assess the efficacy and safety of etanercept in combination with topical therapy using clobetasol propionate for the treatment of moderate to severe plaque psoriasis. The drug was administered at a dose of 50 mg twice a week for 12 weeks, then 50 mg once a week for another 12 weeks. The study included 592 patients, among whom monotherapy was used in 297 and additional local treatment was given to 295 patients. Improvement of 90% after 12 weeks was observed in 65.2% of patients treated with polytherapy and in 48.3% of patients receiving etanercept alone. PASI 75 was achieved in 29.7% and 19.4% of patients, respectively. Adverse events were of comparable frequency in both groups. The addition of a topical drug to etanercept increased efficacy compared with monotherapy without an increase in treatment-related adverse effects.23

Furthermore, some authors conducted a prospective analysis of the effectiveness of etanercept in patients with psoriasis. During a 1-year observation period the effect of etanercept was evaluated on the basis of indicators such as the DLQI and PASI. The study involved 163 patients. From that group, a reduction in skin lesions of more than 50% was observed after 24 weeks in 85% of patients while 81% of patients achieved reductions in skin lesions after 52 weeks. Following treatment, patients reported significant improvements in their quality of life and DLQI decreased on average from 11.4 to 3.2. During the study, none of the patients had serious adverse events.24

Puig et al in the latest research on etanercept draw attention to its potentially beneficial effects on the modulation of insulin sensitivity. In patients with moderate to severe psoriasis, metabolic syndrome is a rather common disorder. In a double-blind study, patients were randomly assigned to a group receiving 50 mg etanercept once or twice a week. At baseline and after 12 weeks, markers such as apolipoprotein (Apo) A1, leptin, CRP and quantitative insulin-sensitivity check index (QUICKI) were assessed. In both the once-weekly and twice weekly dosage groups the values of individual markers were decreased: Apo A1 by 3.5% in the first group and by 4.6% in the second group, CRP by 65.5% and 74.4%, respectively and QUICKI by 2.2% and 2.7%, respectively.25


General information

Adalimumab is a fully human monoclonal antibody which neutralises both free and membrane-bound TNF-α. To date there are few cases where the formation of neutralising antibodies has been observed to reduce the effectiveness of treatment. Adalimumab can be used both in the treatment of psoriasis vulgaris and psoriatic arthritis. In the summary of product characteristics an initial dose of 80 mg is recommended, then 40 mg after a week and 40 mg every 2 weeks as maintenance therapy.3 ,26

Scientific reports

Studies conducted in the Department of Dermatology, Medical University of Łódz´ have shown significant improvements in skin lesions of three patients (PASI 50 in two patients, PASI 75 in one patient) at the 8-week follow-up. In this short treatment period, adverse events associated with the administration of adalimumab have not been observed.21

Ruano et al analysed the long-term effectiveness of adalimumab treatment and compared it with etanercept in patients with plaque psoriasis. Effectiveness of therapy was measured as the proportion of patients achieving PASI 75 during the first 52 weeks of treatment. No statistically significant differences in effectiveness between etanercept and adalimumab were found (PASI 75: 80% vs 85.7%, RR 1.07 (0.90, 1.27); p=0.943).27

Similar results were obtained in a retrospective study which also analysed the response of patients to treatment with etanercept and adalimumab. Out of 4453 patients with psoriasis and psoriatic arthritis, 46.4% of patients treated with etanercept and 56.8% treated with adalimumab responded to 12 months of treatment. Recurrence was noted in 22.4% and 14.9% of patients, respectively.28

In a prospective study, Van den Reek et al analysed patients with psoriasis vulgaris with an insufficient response to adalimumab therapy. Two strategies were used: (1) adalimumab dose escalation (47 patients); and (2) addition of methotrexate to adalimumab (11 patients). For the six patients with the most severe psoriasis the strategies were combined. The effectiveness of therapy was analysed after 12 and 24 weeks using PASI. Of the first group of patients, 25% achieved PASI 50 after 12 weeks and 35% of patients after 24 weeks. In the second group, 9% achieved PASI 50 after 12 weeks of treatment and 18% after 24 weeks. Thus, to increase the effectiveness of a standard treatment with adalimumab (40 mg every other week there are two possible strategies: to increase the dose to 40 mg every week or to combine the therapy with methotrexate.29

In a retrospective study conducted in Spain on a cohort of 119 patients, the effectiveness of treatment with adalimumab was analysed as well as the prevalence of adverse events. The study covered the period from January 2008 to March 2013 with a mean duration of treatment of 25 months (median 22, range 2–60). PASI 75 at 16 weeks, 6 months and 1 year of treatment was achieved in 64%, 58% and 53% of patients, respectively and PASI 90 in this period was achieved in 49%, 52% and 50% of patients. Forty-eight adverse events were observed in 29 patients and serious adverse effects such as tuberculosis were only seen in seven cases (0.032 events per patient-year). Infection with Mycobacterium tuberculosis was the reason for discontinuing treatment in two patients.30

Adverse drug events in patients with psoriasis are mainly due to their immunosuppressive properties. In an extensive article on biological drug therapy it was noted that, during clinical trials of adalimumab, 13 cases of tuberculosis were described. Before starting treatment a Mantoux test is therefore recommended and, if necessary, treatment may be adjusted depending on the diagnosis.31

Other research scientists have reported that, in the vast majority of cases, side effects are short-term, moderately severe and usually local. Occasionally, more serious complications occur such as the worsening of congestive heart failure or the development of lymphoma.32

Biological drugs have a limited risk of adverse drug interactions since they are not metabolised in the liver or kidneys. However, Gupta et al described an interaction between adalimumab and duloxetine and/or pregabalin in a 22-year-old woman with type 1 diabetes mellitus and peripheral neuropathy treated for psoriasis with adalimumab at standard doses. The treatment consisted of duloxetine sustained release 60 mg daily and pregabalin (200 mg three times daily). After the third dose of adalimumab the psoriasis lesions began to improve but her peripheral neuropathy worsened and she experienced excruciating pain in her lower extremities. From these results it is possible that TNF-α inhibitors may indirectly affect the activity of cytochrome P450 (CYP) in the liver and thereby alter the metabolism of some drugs. Further research is needed to validate this relationship since this phenomenon has yet to be confirmed in clinical trials.33

In a multicentre cohort study which included 80 patients with psoriasis vulgaris, the consequences of formation of antidrug antibodies to adalimumab were assessed. Disease severity was examined during a 1-year follow-up period. At baseline and at weeks 12, 24 and 52, blood samples were collected and adalimumab and ADA concentrations were determined. ADA formed in 49% of patients, in 90% of them before 24 weeks. The researchers conclude that, if antibodies against adalimumab are not formed after 24 weeks of treatment, their appearance at a later period is unlikely. Moreover, the presence of ADA is strongly correlated with the concentration of adalimumab and has a significant impact on the reduced clinical response.34

A British study also evaluated the levels of antibodies against adalimumab and the impact of their presence on the course of treatment of psoriasis. In a single-centre cohort of 56 adults with plaque psoriasis, drug and antidrug antibody levels were measured at 4, 12 and 24 weeks of treatment. Patients were divided into responders (PASI 75) and non-responders (failed to achieve PASI 50). After 4 weeks, adalimumab levels were significantly higher in patients responding well to treatment than in non-responders (p=0.003), and these levels persisted after 12 and 24 weeks of treatment. ADA antibodies were detected in 25% of non-responders (2/8 patients) on average after 22.5 weeks of observation and in none of the responders (n=23) on average at 26.1 weeks of follow-up. From these results the authors were able to conclude that early monitoring of drug levels could be useful in predicting the response to treatment.35


The results from research centres around the world confirm the effectiveness as well as the safety of biological drugs and their promising potential in the treatment of psoriasis.14 ,16 ,17 ,22–24 Undoubtedly, these drugs have a significant impact on the improvement in the quality of life in patients with psoriasis and psoriatic arthritis. With these treatments, patients become increasingly self-sufficient and are additionally able to function more comfortably within society.

In order to make simple and informed decisions pertaining to the choice of treatment, one must examine both the benefits and disadvantages that may result from the use of the prescribed drugs. For the first time in scientific history, experts from Germany and the UK performed such comparative analyses of all accessible biological medications in Europe. The effectiveness of these treatments was compared based on currently available randomised clinical trials and estimated on the basis of PASI 50, 75 and 90. Of all the TNF-α inhibitors tested, infliximab demonstrated the highest efficacy, expressed as PASI 50 (93%), PASI 75 (80%) and PASI 90 (54%), followed by adalimumab and etanercept.36

The studies from multiple research centres and expert opinions cited in this article confirm that TNF-α inhibitors (adalimumab, etanercept and infliximab) are a good therapeutic option for patients with moderate to severe psoriasis and psoriatic arthritis who are unresponsive to conventional methods of treatment.

Self assessment questions

Please answer true or false to the below.

  1. In patients with psoriatic arthritis, from the beginning of therapy infliximab should be used along with:

    1. ciclosporin

    2. phototherapy

    3. steroids

    4. methotrexate

    5. retinoids

  2. To increase the effectiveness of a standard treatment with adalimumab there are possible strategies:

    1. increasing the dose to 40 mg every day

    2. increasing the dose to 40 mg every week

    3. combining the therapy with ciclosporin

    4. increasing the dose to 80 mg every week

    5. combining the therapy with methotrexate

  3. Infliximab is a:

    1. IL-12 inhibitor

    2. TNF-α blocker

    3. IL-23 inhibitor

    4. B-cell inhibitor

    5. T-cell inhibitor

  4. Etanercept is administered:

    1. intramuscularly

    2. orally

    3. subcutaneously

    4. intravenously

    5. sublingual

  5. Recommended doses of adalimumab are:

    1. 25 mg twice a week or 50 mg once a week

    2. an initial dose of 80 mg, then 40 mg after a week, and 40 mg every 2 weeks as maintenance therapy

    3. 5 mg/kg body weight and is given at 0, 2 and 6 weeks, then every 8 weeks

    4. 45 mg every 12 weeks

    5. 0.7 mg/kg body weight and then 1.0 mg/kg every week

Main messages

  • Psoriasis is a chronic immunological disease.

  • The classic management using topical (vitamin D3, cygnoline, keratolytic drugs, corticosteroids, vitamin A analogues, tars, phototherapy) and systemic agents (retinoids, ciclosporin A, methotrexate) is often long-term, difficult and does not bring about ideal results.

  • Patients with psoriasis usually experience a significantly decreased quality of life.

  • Currently, dermatological treatment of psoriasis and psoriatic arthritis is possible with TNF-α blockers, inhibitors of IL-12 and IL-23, T cell inhibitors as well as B cell inhibitors.

  • Biological therapy for psoriasis and psoriatic arthritis is subject to specific requirement and to guidelines.

  • Adalimumab, etanercept and infliximab, through TNF-α uptake, block the proinflammatory effects of this cytokine which clinically manifests as remission of symptoms.

  • TNF-α blockers are a good therapeutic option for patients with moderate to severe psoriasis and psoriatic arthritis who are unresponsive to conventional methods of treatment.

Current research questions

  • What are the current European criteria for the use of biological treatment for patients with psoriasis vulgaris and psoriatic arthritis?

  • For what are neutralising antibodies (HACA, human antichimeric antibodies) responsible?

  • What are the other possibilities of biological therapy besides TNF-α blockers for patients with psoriasis?

  • What are the side effects of molecularly targeted therapy of psoriasis and psoriatic arthritis?

Key references

  • Szepietowski J, Adamski Z, Chodorowska G, et al. Guidelines of Polish Dermatological Society on the treatment of psoriasis vulgaris and arthropathic psoriasis (psoriatic arthritis) with biological drugs. Przegl Dermatol 2010;97:1–13.

  • Marques P, Filipe P. Guidelines for high-quality use of biologic therapies in adults with plaque psoriasis. Acta Med Port 2012;25:125–41.

  • Puig L, Carrascosa J, Carretero G, et al. Spanish evidence-based guidelines on the treatment of psoriasis with biologic agents, 2013. Part 1: On efficacy and choice of treatment. Actas Dermosifiliogr 2013;104:694–709.

  • Coates L, Tillett W, Chandler D, et al. The 2012 BSR and BHPR guideline for the treatment of psoriatic arthritis with biologics. Rheumatology 2013;52:1754–7.

  • Reich K, Burden AD, Eaton JN, et al. Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials. Br J Dermatol 2012;166:179–88.


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View Abstract


  • Contributors DW-D, MZ-N, LB-W, UM were responsible for the concept and design of the study, collection and collation of data, analysis and interpretation of data, writing and reviewing the article, final reviewing of the article and preparing the graphics.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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