*2.3.5 Apremilast*

Apremilast, operating as a selective inhibitor of phosphodiesterase 4, on the one hand downregulates the expression of specific proinflammatory cytokines like IL-17, IL-23 and TNF-α that each plays a crucial role in the pathophysiological chain of events in psoriasis. On the other hand, using the same mechanism, it increases the expression of anti-inflammatory cytokines such as IL-10 [59].

*Dosage and administration*. Presented in tablet form, apremilast is administered orally, with an indicated dose of 30 mg two times per day. The treatment should begin with a low starting dose of 10 mg in the morning, and then from the second day of therapy onward the dosage is increased daily by 10 mg until reaching the therapeutic dose of 30 mg twice daily [60, 61].

*Adverse effects*. Diarrhoea, nausea and vomiting, depression and weight loss are the most frequently noted adverse effects of apremilast [62].

*Laboratory tests recommended*. Physical exam, patient history (with an emphasis on psychiatric disorders such as depression), renal function and liver enzymes should be performed.

*Drug interactions*. Apremilast interacts with cytochrome P450 enzyme inducers such as rifampin, phenobarbital, carbamazepine and phenytoin [61].

Patients over 65 years old appear to be more vulnerable to develop the aforementioned side effects. Hence, supervision is very important in these cases, patients being warned regarding undesirable events. They should also be instructed not to reduce or suspend the medication by themselves, but to address their treating physician [62].

### **2.4 Biologic therapies**

#### *2.4.1 The anti-TNF-α agents*

The anti-TNF-α agents etanercept, adalimumab, infliximab and certolizumab have been developed to expressly inhibit the TNF-α signalling pathway, thereby lessening its inflammatory properties. Etanercept is a recombinant TNF-α receptor that impedes TNF-α function by operating as a decoy receptor that attaches to TNF. Adalimumab is an entirely humanized antibody of TNF-α, where infliximab is a mouse-human chimeric antibody. Certolizumab represents a distinctive anti-TNF-α antibody that does not include the Fc portion [63, 64].

*Dosage and administration*. Etanercept, adalimumab and certolizumab are given via subcutaneous injection either weekly or once every two weeks. Infliximab is administered via intravenous infusion every 8 weeks. **Table 1** presents the dosage and the administration method for the abovementioned anti-TNF-α agents [65–68].

*Adverse effects*. Among the serious side effects encountered while using any of the mentioned anti-TNF-α agents are severe infections, lymphomas or other malignancies and even the reactivation of the tuberculosis or hepatitis B virus. While using etanercept, adalimumab or certolizumab, the most usual local reactions are pain, swelling, haemorrhage or erythema at the place of injection; however, the intensity of these symptoms will diminish with continued treatment. Patients should be advised not to accept taking live vaccinations for the duration of the therapy. There have been reported cases of CNS demyelinating pathologies (e.g. multiple sclerosis, optic neuritis) or peripheral nerve demyelinating disease (Guillain-Barré syndrome). Patients are advised to suspend the therapy in these cases [3, 65–68].

*Laboratory tests recommended*. Physical exam and history, complete blood count, liver function, renal function, viral hepatitis screening and tuberculosis testing should be performed prior to anti-TNF-α treatment initiation.

*Drug interactions*. Other biologic therapies, live vaccines, anakinra and abatacept, were noticed to interact with anti-TNF-α drugs [65–68].

Certolizumab has been approved by the FDA for pregnant women. Data collected thus far has validated neither additional teratogenic effects when compared to the general population, nor a greater risk of foetal death [69].

#### *2.4.2 The anti-IL-12/23 agents*

The anti-IL-12/23 agents comprise ustekinumab, guselkumab and tildrakizumab. Il-23 is a heterodimeric cytokine incorporating two subunits: the p19 subunit, which is connected to the p40 subunit, the latest being shared with IL-12. Il-23 is the main actor prompting the activation of the T helper 17 inflammatory pathway, whereas IL-12 plays the chief role in Th-1 differentiation and proliferation. Ustekinumab is a biologic agent aiming for the p40 common domain of IL-12 and IL-23, hence preventing their interaction with their receptor. Contrariwise, guselkumab and tildrakizumab target the p19 subunit of IL-23, thus obstructing the signalling pathway associated with the immunopathogenesis of psoriasis [70–72].

*Dosage and administration*. Ustekinumab, guselkumab and tildrakizumab are delivered as prefilled syringes with subcutaneous administration. The induction phase lasts 1 month, being then ensued by the maintenance phase. In this phase, an injection is administered once every 8 or 12 weeks. **Table 2** presents the respective posology for the aforementioned biologic agents [73–75].

**95**

*Medical Management of Chronic Plaque Psoriasis in the Modern Age*

one injection weekly

*Adverse effects*. The most notable and grave adverse effects include severe infections, tuberculosis, malignancies, hypersensitivity reactions, headache, fatigue,

Ustekinumab 45 mg × 1 administered at weeks 0 and 4 and at every 12 weeks subsequently Guselkumab 100 mg × 1 administered at weeks 0 and 4 and at every 8 weeks afterwards Tildrakizumab 100 mg × 1 administered at week 0 and 4 and every 12 weeks thereafter

Etanercept 50 mg × 1 twice a week during the induction phase (the first 3 months), thereafter only

Infliximab 5 mg/kg is administered via intravenous infusion at weeks 0, 2 and 6 and after that every

Certolizumab 200 mg × 2 administered subcutaneously at weeks 2 and 4, followed by a 200 mg × 1 dose

Adalimumab 40 mg × 2 at week 0, afterwards 40 mg × 1 administered every 14 days

*Laboratory tests recommended*. Physical exam, patient history, complete blood count, liver function, renal function and tuberculosis testing have to be performed

*Drug interactions*. These agents have been noticed to interact with live vaccines. Therefore, it is contraindicated to receive any such vaccines during therapy [3, 73–75].

Ixekizumab, secukinumab and brodalumab are systemic anti-IL-17 agents that carry out their roles by expressly inhibiting the IL-17 signalling pathway. Ixekizumab is a humanized IgG4 antibody with a high affinity for IL-17A [76]. Secukinumab is a fully human IgG1 antibody that also blocks IL-17A. Last but not least, brodalumab is a fully human IgG2 antibody that impedes the IL-17 pathway at the receptor level, i.e. by binding to the IL-17RA, a receptor shared by IL-17A and other IL-17 cytokines. For this reason, its effect is broader but more

*Dosage and administration*. Ixekizumab, secukinumab and brodalumab are administered as prefilled subcutaneous injections. The induction phase varies from 3 to 12 weeks, followed by the maintenance phase with one or two injections either every second or monthly. **Table 3** illustrates the posology of these therapies [78–80]. *Adverse effects*. Anti-IL-17 agents may cause serious infections, headache, joint pain, hypertension, diarrhoea, injection site reaction (oedema, pain, erythema,

*Laboratory tests recommended*. Physical exam, patient history, complete blood count, liver function, renal function and tuberculosis testing must be performed

*Drug interaction*. These agents may interact with drugs that are metabolized by

ecchymosis), musculoskeletal pain and hypersensitivity reactions [81].

cytochrome P450, e.g. warfarin or cyclosporine [78–80].

injection site reaction, joint pain and gastroenteritis [73–75].

*2.4.3 Ixekizumab, secukinumab and brodalumab*

before treatment can begin.

**Biologic agent Posology**

*Anti-TNF-α agents. Posology.*

*Anti-IL-22/anti-IL-23 agents. Posology.*

**Table 2.**

**Table 1.**

unspecific [77].

before these therapies as well.

*DOI: http://dx.doi.org/10.5772/intechopen.90626*

8 weeks

weekly

**Biologic agent Posology**

*Medical Management of Chronic Plaque Psoriasis in the Modern Age DOI: http://dx.doi.org/10.5772/intechopen.90626*


**Table 1.**

*Healthcare Access - Regional Overviews*

their treating physician [62].

*2.4.1 The anti-TNF-α agents*

**2.4 Biologic therapies**

instructed not to reduce or suspend the medication by themselves, but to address

The anti-TNF-α agents etanercept, adalimumab, infliximab and certolizumab have been developed to expressly inhibit the TNF-α signalling pathway, thereby lessening its inflammatory properties. Etanercept is a recombinant TNF-α receptor that impedes TNF-α function by operating as a decoy receptor that attaches to TNF. Adalimumab is an entirely humanized antibody of TNF-α, where infliximab is a mouse-human chimeric antibody. Certolizumab represents a distinctive anti-

*Dosage and administration*. Etanercept, adalimumab and certolizumab are given via subcutaneous injection either weekly or once every two weeks. Infliximab is administered via intravenous infusion every 8 weeks. **Table 1** presents the dosage and the administration method for the abovementioned anti-TNF-α agents [65–68]. *Adverse effects*. Among the serious side effects encountered while using any of the mentioned anti-TNF-α agents are severe infections, lymphomas or other malignancies and even the reactivation of the tuberculosis or hepatitis B virus. While using etanercept, adalimumab or certolizumab, the most usual local reactions are pain, swelling, haemorrhage or erythema at the place of injection; however, the intensity of these symptoms will diminish with continued treatment. Patients should be advised not to accept taking live vaccinations for the duration of the therapy. There have been reported cases of CNS demyelinating pathologies (e.g. multiple sclerosis, optic neuritis) or peripheral nerve demyelinating disease (Guillain-Barré syndrome). Patients are advised to suspend the therapy in these cases [3, 65–68].

*Laboratory tests recommended*. Physical exam and history, complete blood count, liver function, renal function, viral hepatitis screening and tuberculosis testing

*Drug interactions*. Other biologic therapies, live vaccines, anakinra and abata-

Certolizumab has been approved by the FDA for pregnant women. Data collected thus far has validated neither additional teratogenic effects when compared

The anti-IL-12/23 agents comprise ustekinumab, guselkumab and tildrakizumab. Il-23 is a heterodimeric cytokine incorporating two subunits: the p19 subunit, which is connected to the p40 subunit, the latest being shared with IL-12. Il-23 is the main actor prompting the activation of the T helper 17 inflammatory pathway, whereas IL-12 plays the chief role in Th-1 differentiation and proliferation. Ustekinumab is a biologic agent aiming for the p40 common domain of IL-12 and IL-23, hence preventing their interaction with their receptor. Contrariwise, guselkumab and tildrakizumab target the p19 subunit of IL-23, thus obstructing the signalling pathway associated with the immunopathogenesis of psoriasis [70–72]. *Dosage and administration*. Ustekinumab, guselkumab and tildrakizumab are delivered as prefilled syringes with subcutaneous administration. The induction phase lasts 1 month, being then ensued by the maintenance phase. In this phase, an injection is administered once every 8 or 12 weeks. **Table 2** presents the respective

TNF-α antibody that does not include the Fc portion [63, 64].

should be performed prior to anti-TNF-α treatment initiation.

cept, were noticed to interact with anti-TNF-α drugs [65–68].

to the general population, nor a greater risk of foetal death [69].

posology for the aforementioned biologic agents [73–75].

*2.4.2 The anti-IL-12/23 agents*

**94**

*Anti-TNF-α agents. Posology.*


#### **Table 2.**

*Anti-IL-22/anti-IL-23 agents. Posology.*

*Adverse effects*. The most notable and grave adverse effects include severe infections, tuberculosis, malignancies, hypersensitivity reactions, headache, fatigue, injection site reaction, joint pain and gastroenteritis [73–75].

*Laboratory tests recommended*. Physical exam, patient history, complete blood count, liver function, renal function and tuberculosis testing have to be performed before treatment can begin.

*Drug interactions*. These agents have been noticed to interact with live vaccines. Therefore, it is contraindicated to receive any such vaccines during therapy [3, 73–75].

### *2.4.3 Ixekizumab, secukinumab and brodalumab*

Ixekizumab, secukinumab and brodalumab are systemic anti-IL-17 agents that carry out their roles by expressly inhibiting the IL-17 signalling pathway. Ixekizumab is a humanized IgG4 antibody with a high affinity for IL-17A [76]. Secukinumab is a fully human IgG1 antibody that also blocks IL-17A. Last but not least, brodalumab is a fully human IgG2 antibody that impedes the IL-17 pathway at the receptor level, i.e. by binding to the IL-17RA, a receptor shared by IL-17A and other IL-17 cytokines. For this reason, its effect is broader but more unspecific [77].

*Dosage and administration*. Ixekizumab, secukinumab and brodalumab are administered as prefilled subcutaneous injections. The induction phase varies from 3 to 12 weeks, followed by the maintenance phase with one or two injections either every second or monthly. **Table 3** illustrates the posology of these therapies [78–80].

*Adverse effects*. Anti-IL-17 agents may cause serious infections, headache, joint pain, hypertension, diarrhoea, injection site reaction (oedema, pain, erythema, ecchymosis), musculoskeletal pain and hypersensitivity reactions [81].

*Laboratory tests recommended*. Physical exam, patient history, complete blood count, liver function, renal function and tuberculosis testing must be performed before these therapies as well.

*Drug interaction*. These agents may interact with drugs that are metabolized by cytochrome P450, e.g. warfarin or cyclosporine [78–80].


**Table 3.**

*Anti-IL-17 agents. Posology.*
