Biologic Therapies for Dermatology Conditions



Biologic Therapies for Dermatology Conditions


Lakshi M. Aldredge





LEARNING OBJECTIVES

After studying this chapter, the reader will be able to:



  • Identify common biologic agents used in the treatment of dermatologic conditions.


  • Understand clinical criteria, side effects, and monitoring parameters of biologic agents.


  • Counsel patients and other health care providers regarding proper use and side effect monitoring of biologic agents.



KEY POINTS



  • Appropriate identification of patients who are candidates for biologic therapy is important. A thorough knowledge of their medical history, current medication profile, and family history of medical conditions must be ensured.


  • Patients must be aware of the risks and benefits of biologic therapy including their side effect profile, the need for close monitoring, and consistent follow-up with their dermatology provider.


  • Patients need to be appropriately counseled regarding healthy lifestyle modifications in order to ensure successful outcomes with their biologics, including smoking cessation, appropriate immunization practices, and diet and weight control.


I. OVERVIEW

Biologic agents (biologic response modifiers) are proteinbased drugs targeting specific inflammatory immune mediators that contribute to the development of cutaneous and systemic disorders. They are the newest therapeutic modalities used to treat dermatologic and other conditions. These agents are derived from biologic synthesis using living cells rather than a chemical process.

Because they are large protein molecules, there are no oral biologic agents and they must, therefore, be administered either subcutaneously or intravenously. Biologics tend to initiate a significant therapeutic response within a relatively short time period and are highly efficacious, often providing 50% to 75% improvement in most patients. Because they target specific immune markers, such as cytokines, enzymes, and growth factors, they are considered less likely to cause end-organ toxicity as compared to traditional systemic agents, such as methotrexate and cyclosporine. However, due to their immune-modifying ability, some agents may be associated with increased risk of infection and malignancy as well as other side effects. Biologic agents have also been associated with the development of antidrug antibodies, which may inhibit long-term use. Patients should be carefully screened in order to determine if they are an appropriate candidate for biologic therapy because of the aforementioned risks.

Most patients find biologic agents convenient to use and well tolerated compared with other therapies, such as conventional systemics and phototherapy. They are an expensive alternate to conventional systemic agents and most insurance carriers require failure of one or more traditional therapies prior to authorization of a biologic. Traditionally approved for use in psoriatic disease, biologics are now being studied in other challenging dermatology conditions. As researchers and scientists continue to discover new immune-mediated therapeutic targets for dermatologic conditions, newer biologic agents are being developed that will continue to significantly impact the way in which dermatologic conditions are managed in the near future.


II. BIOLOGICS IN TREATMENT OF PSORIASIS

A. Overview

1. Psoriasis is a common autoimmune inflammatory disorder characterized by hyperproliferation of keratinocytes resulting in thickened, scaling plaques and may be accompanied by inflammation and destruction of joints and enthesis (areas where tendons/ligaments bind to bone). It is associated with numerous comorbidities including cardiovascular disease, metabolic disorders, and psychosocial conditions. In addition to the physical symptoms associated with psoriasis, this complex condition can result in significant impairment in patients’ quality of life (see Chapter 8).

2. The pathogenesis of psoriasis is highly complex, and while the exact cause is unknown, it is thought to be
a T-cell-mediated disease involving the production of inflammatory cytokines such as tumor necrosis factor (TNF), interleukins (IL-23, IL-17), and other mediators. There is no cure for psoriasis, although research in the past two decades has helped to identify immunological pathways that lead to psoriatic disease development and progression. The therapies focusing on these immunological pathways are known as biologics.

3. The first biologic agent approved for psoriasis by the U.S. Food and Drug Administration (FDA) was alefacept in 2003. The company took it off the market in 2011. In the United States, there are currently four biologic agents approved for psoriasis: adalimumab, etanercept, infliximab, and ustekinumab. These four biologic agents used in the treatment of psoriasis are summarized in Table 5-1. Adalimumab, etanercept, and infliximab are TNF-alpha inhibitors, and ustekinumab is an IL-12/IL-23 blocker.








TABLE 5-1 Biologic Agents for Psoriasis















































Agent

Mechanism of Action

Dosing

Screening

Efficacy

Side Effects


Adalimumab (Humira)

TNF-α inhibitor

80 mg SC week 0, then 40 mg 7 days later, then 40 mg every other week

Baseline: Hepatitis B, TB, CBC, LFTs, and chemistry panel Annual: TB Periodic CBC, LFTs, and chemistry panels as warranted

53%-80% of patients achieved PASI 75 with doses of 40 mg every other week and 40 mg every week, respectively

Common: Injection site reactions, URI, headache, and fatigue.


Rare: Serious infection including TB, malignancy, hepatitis B reactivation, development of positive antinuclear antibodies, development of lupus-like syndrome anaphylaxis, and new-onset demyelinating disease


Etanercept (Enbrel)

TNF-α inhibitor

50 mg SC twice a week × 3 months, then 50 mg every week

Baseline: Hepatitis B, TB, CBC, LFTs, and chemistry panel Annual: TB Periodic CBC, LFTs, and chemistry panels as warranted

Approximately 30% of patients treated with 25 mg BIW achieved PASI 75 after 12 weeks.


50% of patients treated with 50 mg BIW achieved PASI 75

Common: Injection site reactions, URI, headache, and fatigue.


Rare: Serious infection including TB, malignancy, hepatitis B reactivation, new-onset or worsening CHF, pancytopenia, development of positive antinuclear antibodies, development of lupus-like syndrome anaphylaxis, and new-onset demyelinating disease


Infliximab (Remicade)

TNF-α inhibitor

5 mg/kg IV infusion weeks 0, 2, and 6 and then every 8 weeks

Baseline: Hepatitis B, TB, CBC, LFTs, and chemistry panel Annual: TB Periodic CBC, LFTs, and chemistry panels as warranted

75% of patients receiving 5 mg/kg achieved a PASI 75 at week 10

Common: URI, headache, and fatigue Rare: Acute infusion site reactions, delayed hypersensitivity reaction (myalgia, arthralgia, fever, rash, pruritus, edema, dysphagia, urticaria, sore throat, headache), serious infection including TB, malignancy, hepatitis B reactivation, new-onset or worsening CHF, pancytopenia, development of positive antinuclear antibodies, development of lupus-like syndrome anaphylaxis, and new-onset demyelinating disease


Ustekinumab (Stelara)

Blocks the p40 subunit of IL-12/IL-23

45 mg (patients <100 kg) and 90 mg (patients over 100 kg) weeks 0 and 4 and then every 12 weeks thereafter

Baseline: TB Can consider CBC, LFTs, and chemistry panel Annual: TB Periodic CBC, LFTs, and chemistry panels as warranted

45 mg dosing: 65% of patients achieved PASI 75.


90 mg dosing: 76% of patients achieved PASI 75

No clear side effect patterns emerged in clinical trials.


However, there is a risk for injection site reactions, and because it targets the immune system, there is a theoretical risk of serious infection and malignancy. There is one reported case of posterior leukoencephalopathy syndrome


Secukinumab (Cosentyx)

IL-17A agonist

150 or 300 mg SC Week 0, 1, 2, 3, 4 and then every 4 weeks thereafter

Baseline: TB Can consider CBC, LFTs, chemistry panel Annual: TB Periodic CBC, LFTs, chemistry panels as warranted

150 mg dosing: 71.6% of patients achieved PASI 75 at week 12 300 mg dosing: 81.6% of patients achieved PASI 75 at week 12

No clear side effect patterns emerged in clinical trials. There was an increase in Crohn disease exacerbations during clinical trials, and as such, secukinumab should be used cautiously in this population. Because it targets the immune system, there is a theoretical risk of increased risk of infection and malignancy.


TNF-α, tumor necrosis factor alpha; CBC, complete blood count; TB, tuberculosis.


4. Patient education for patients with psoriasis considering the use of these biologic agents is essential. Important points to emphasize are noted in Box 5-1.

B. TNF-alpha (TNF-α) blockers

1. Overview

a. TNF-α blockers are the most common biologics used in the treatment of psoriasis and psoriatic arthritis worldwide.




BOX 5-1. Use of Biologic Agents in Psoriasis: Patient Screening, Education, and Monitoring

Patients should be advised that as there is no cure for psoriasis, treatment with biologic agents must be consistent and ongoing.

Only gold members can continue reading. Log In or Register to continue

Related posts:

  1. Dermatologic Diagnostic Tests and Procedures
  2. Dermatitis/Eczemas
  3. Photodamage, Photodermatoses, and Aging Skin
  4. Cutaneous Manifestations of Systemic Disease

Stay updated, free articles. Join our Telegram channel
Tags:
Mar 9, 2021 | Posted by in NURSING | Comments Off on Biologic Therapies for Dermatology Conditions

Full access? Get Clinical Tree
Get Clinical Tree app for offline access