Abstract

Psoriasis (PsO) is an autoimmune disease where skin cells build up and form scaly, itchy, and dry patches. PsO is a lifelong disease with spontaneous remission and exacerbation. Up to 30% of patients will also have psoriatic arthritis (PsA) which consists of joint inflammation, pain, stiffness, and swelling. Currently, there is no cure for PsO and PsA, so treatments are focused more on alleviating symptoms, reducing disease severity, and improving quality of life. The goal of this article is to examine treatment selections of biologics for patients with moderate-severe PsO and PsA. Most biologics included in this article, with the exception of etanercept, will allow at least 70% of PsO patients to experience a 75% improvement after 3 months and at least 50% of PsA patients to experience at least a 20% improvement after 6 months. The patient’s insurance coverage, comorbidities, and dosing preference are major factors that should be taken into consideration when selecting a biologic.

Purpose

To examine treatment selections of biologics for moderate-severe psoriasis (PsO) and psoriatic arthritis (PsA)

Introduction

Psoriasis is an autoimmune disease where skin cells build up and form scaly, itchy, and dry patches. This autoimmune inflammatory response is triggered by a variety of factors including infection, stress, and cold weather. As a result, the skin may appear inflamed and develop silvery-white scaly papules, or dry plaques. These plaques commonly occur on the scalp, elbows, knees, and limbs. Common symptoms include itching, irritation, burning, and stinging.(1) Most symptoms begin to occur due to T cell-mediated hyperproliferation of keratinocytes, which causes abnormal differentiation of epidermal cells and thickening of the skin.(1) PsO is a lifelong disease with spontaneous remission and exacerbation. Up to 30% of patients will also have psoriatic arthritis (PsA) which consists of joint inflammation, pain, stiffness, and swelling.(2) The chemical signals involved in the inflammatory pathways that occur in patients with PsA can also contribute to the augmented inflammation underlying other systemic diseases including metabolic syndrome and cardiovascular disease.(3) Patients with PsA can benefit from treatment with a biologic. Patients who have PsO but not PsA can also benefit from this treatment if other treatments have failed.

Diagnosis

About 90% of psoriasis is plaque psoriasis, which is characterized by round or oval plaques of different sizes that coalesce to form a large patch on the skin.(1) In clinical practice, severity is assessed based on characteristics of the plaque, response to treatment, quality of life, and total body surface affected. Usually, if plaque is more than 5% of the body surface area (BSA) or causes physical or mental impairment, it is considered moderate-severe.(1) A patient’s case may be considered severe when BSA is less than 5% if the plaque occurs on vital areas such as the face, hands, feet, scalp, or intertriginous areas in a manner that cause the patient significant disability.(2) For patients with PsA, the diagnosis is based on a medical history of joint pain, swollen fingers or toes, abnormalities of nails, heel pain, and/or lower back pain.(4) Further screening with physical examination of swelling and inflammation, blood tests for rheumatoid factor and sedimentation rate, and imaging scans such as magnetic resonance imaging or X-ray may help determine the characteristics and severity of psoriatic arthritis.(4)

Treatment Guide

There is no cure for PsO nor PsA. Therefore, treatment is focused more on alleviating symptoms, reducing disease severity, and improving quality of life. Figure 1 outlines the treatment guide below.

  • For mild-moderate PsO (<5% BSA), common treatments include topical over-the-counter (OTC) moisturizers, corticosteroids, Vitamin D analogs (calcipotriene, calcitriol), and retinoid.(1)

  • For moderate-severe PsO (>5% BSA), common treatments include OTC moisturizers, Vitamin D analogs, phototherapy, and traditional systemic agents such as methotrexate, cyclosporine, or acitretin.(1)

    • -

      BSA < 20%: Vitamin D analog with or without phototherapy.

    • -

      BSA > 20%: Traditional systemic agent with or without phototherapy.(1)

      • Traditional systemic agents may take up to four months to reach optimal control of psoriasis symptoms.

      • Healthcare providers should consider switching to a biologic if the treatment fails or a patient experiences intolerable side effects or adherence problems.

  • For PsA, common treatments include OTC moisturizers and biologic agents. Biologics can prevent worsening of joints and reduce joint pain, inflammation, stiffness, and swelling.(3)

Biologic Selection

Biologics are effective in treating PsO with or without PsA. With the exception of etanercept, most of these biologics will allow at least 70% of PsO patients to experience a 75% improvement after 3 months and at least 50% of PsA patients to experience at least a 20% improvement after 6 months. Patients should be prescribed with an agent that is covered by their insurance since the biologic agents are expensive. Note that there is no significant evidence for choosing one biologic over another. However, the American College of Rheumatology suggests that a treatment-naïve patient can start with a tumor necrosis factor inhibitor (TNFi) biologic.(4) If a TNFi biologic is determined to be ineffective by the provider after 3 months or if the disease worsens, then the patient may switch to another TNFi, interleukin 17 inhibitor (IL17i), or interleukin 12/23 inhibitor (IL12/23i) biologic.(4) Patients who have heart failure, multiple sclerosis, or a first-degree relative with multiple sclerosis may want to avoid using TNFi agents because they have been shown to exacerbate these conditions.3 Below is a suggested treatment outline. (Drugs below are FDA approved for PsO and PsA, with the exception of golimumab which is only FDA approved for PsA)

  • Initial Drug of Choice: if covered by the patient’s insurance, the patient can start with a TNFi like adalimumab.(4)

    • -

      Adalimumab and certolizumab pegol are both subcutaneous (subq) TNFi injections that are given once every other week.(5) However, certolizumab pegol is more expensive, has more drug-drug interactions, and causes urinary tract infections.(57) Therefore, patients should start with adalimumab and monitor for common side effects such as headache, rash, and signs of infections.(6)

    • -

      Golimumab, which requires only one subcutaneous injection per month, is an option for patients who prefer a less frequent dosing TNFi. However, golimumab is more expensive than both adalimumab and certolizumab pegol .(6,7)

    • -

      Infliximab and etanercept are among the earlier FDA approved biologic agents for PsO/PsA, however these drugs are inconvenient. Infliximab is an intravenous agent so it must be administered at a doctor’s office at weeks 0, 2, and 6, then every 8 weeks.(6) However, infliximab’s maintenance cost is about $2,272 per month which makes it the most affordable biologic option.(7) Etanercept requires twice weekly subcutaneous administration for the first 3 months then weekly administration for maintenance.(6)

    • -

      Adalimumab, certolizumab pegol, and infliximab may be beneficial for patients with concomitant inflammatory bowel disease because they also have indications for Crohn’s disease.(4,6)

  • If the patient does not respond to adalimumab:

    • -

      Option 1: The patient can be prescribed an alternate TNFi (certolizumab pegol, golimumab, infliximab, etanercept)

    • -

      Option 2: The patient can be prescribed an IL17i (ixekizumab, secukinumab)

      • Ixekizumab is more effective than secukinumab for the treatment of PsA.(5) 58% of adults with PsA experienced at least a 20% improvement after 6 months with ixekizumab, but only 51% experienced the improvement with secukinumab.(5) Both have a warning and precaution label that states that patients with inflammatory bowel disease must be monitored closely.(6) It may be safer for these patients to switch to a TNFi rather than a IL17i. Injection site reaction is more prominent with ixekizumab with an incidence of ~17% in the ixekizumab group compared to 3% in the placebo group.(7) Both ixekizumab and secukinumab have similar pricing of approximately $6000 per month based on their maintenance dose of one subcutaneous injection every four weeks.(9)

    • -

      Option 3: The patient can be prescribed an IL12/23i (ustekinumab)

      • Ustekinumab has the least frequent dosing out of all of the biologics. It is given at weeks 0, 4, then every 12 weeks.(6) It can be used in children 12 years of age and older while other biologics are only indicated for adults 18 years and older.(6) Ustekinumab may be an initial agent of choice for patients who are not compliant and prefer the least frequent dosing. However, ustekinumab has a higher monthly cost than most of the other biologics so ustekinumab should only be prescribed if it is covered by the patient’s insurance.(9)

If a patient cannot do intravenous or subcutaneous administration, Oteza is an oral option. The dosage frequency is once on the first day, then twice daily. However, it is not preferable for patients with a history of mental health illness because it has a warning and precaution label for emergence or worsening of depression, suicidal thoughts, and weight loss.(6) Moreover, Oteza metabolism is primarily mediated by Cytochrome P450 3A4 which may lead to drug-drug interactions.

Considerations for use of biologic agents as treatment

Biologics have shown to be a treatment option for conditions outside of psoriasis. A recent study has shown that the use of biologics in PsA patients may reduce coronary artery plaque by 8% which can prevent cardiovascular diseases such as heart attacks and strokes.(8) As a result of reducing the activity of the immune system, biologics decrease inflammation, blood flow restriction, and artery blockages that leads to these cardiovascular diseases.(8) Moreover, biologics may be an option for PsA patients who have liver and kidney concerns because biologics are less likely to cause damage to other organs than other non-biologic agents for psoriasis.(8)

Although biologics are treatment options for moderate-severe PsO cases, these agents are more expensive, and their failure may lead to higher healthcare costs. As a result, biologics are reserved for when PsO patients have failed other therapies or when patients also have PsA.(9) In addition, biologics suppress the immune response which may lead to an increased risk of developing a serious infection. This risk increases in elderly patients and those who have diabetes, a history of infections, or are current tobacco users.(9) Smoking cessation is recommended for adult patients with PsA to reduce disease progression.(9) PsA patients with a history of frequent infections should begin their therapy with an oral small molecule (methotrexate, sulfasalazine, leflunomide, cyclosporine, or apremilast) instead of a biologic.(9) Patients should not take biologics if they have active tuberculosis (TB), a positive TB test that has not been treated, or an active infection.(9)

New Treatments

Newly approved IL-23 inhibitors (Tildrakizumab, Risankizumab, Guselkumab) and topical Duobrii (halobetasol propionate and tazarotene) were not reviewed in this article. Their place in therapy is to be determined.

Key Points

  • Patients with moderate-severe PsO who have failed other treatments and patients with PsA may benefit from using a biologic.

  • Most biologics listed in Table 1, with the exception of etanercept, will allow at least 70% of PsO patients to experience a 75% improvement after 3 months and at least 50% of PsA patients to experience at least a 20% improvement after 6 months.

Selecting a biologic depends on the patient’s insurance, comorbidities, and dosing preference (refer to Table 1 and ‘Biologic Selection’ section).

Abbreviations Used

     
  • BSA

    body surface area

  •  
  • DOC

    drug of choice

  •  
  • IL12/23i

    interleukin 12/23 inhibitor

  •  
  • IL17i

    interleukin 17 inhibitor

  •  
  • IV

    intravenous

  •  
  • kg

    kilograms

  •  
  • mg

    milligram

  •  
  • OTC

    over-the-counter

  •  
  • PsO

    psoriasis

  •  
  • PsA

    psoriatic arthritis

  •  
  • subq

    subcutaneous

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About the Authors

Vivian Dang, PharmD, is a pharmacist and data scientist. She graduated from the University of Maryland School of Pharmacy in 2019 and completed the Flatiron School’s data science bootcamp in 2020. She is experienced with direct patient care, clinical research , and data processing. Dr. Dang has no conflicts of interest to report.

Craig S. Stern, RPh, PharmD, MBA, FASCP, FASHP, FICA, FLMI, FAMCP, FCPhA, CSP is the president of Pro Pharma Pharmaceutical Consultants in Chatsworth, CA, a professor pharmacy at the University of Southern California, University of California, San Francisco and Western University of Health Sciences, and an adjunct professor and preceptor at the University of the Pacific. He is a fellow of the Academy of Managed Care Pharmacy, the American Society of Consultant Pharmacists and the American Society of Health-System Pharmacists. Dr. Stern has no conflicts of interest to report.