Before we dive into our discussion, let’s outline the Guideline-Based Approach to Treatment Selection.
The International Psoriasis Council has divided psoriasis treatment classification into 2 groups:
- Patients who are a candidate for topical therapy, or
- Patients who are a candidate for systemic therapy
Candidates for systemic therapy must meet at least 1 of the following criteria:
- BSA >10%
- Involvement of special sites: Face, palms/soles, genitals
- Failed topical therapies
Let’s start with topical therapies in psoriasis. Our goal with topical therapy is to treat a patient to clear or almost clear. Dr. Armstrong recommends a “proactive approach” in topical treatments. Once patients have treated psoriasis flares and maintained clearance, it is important to continue treatment of these clinically quiescent areas. Instead of stopping treatment altogether, advise the patient to continue treating those areas twice weekly to maintain clearance. This proactive treatment approach may help prevent flares and provide better long-term control. Topical steroid and non-steroid treatments can be mixed and matched for maintenance treatment.
There is a new player in topical psoriasis treatment: Tapinarof is an aryl hydrocarbon receptor agonist that decreases Th17 cytokines resulting in decreased psoriatic inflammation. Patients using tapinarof cream once daily achieved improvement of psoriatic lesions over 12 weeks. Once stopped, patients remained clear at 12 weeks and 24 weeks. This is novel finding in topical therapies.
Let’s move onto systemic therapies. Methotrexate (MTX) is an old school player but a good option in the following patient populations:
- Lack health insurance
- Psoriatic arthritis with lack of coverage for biologics
- Combined with biologic or phototherapy
It is important to note that MTX is contraindicated in patients with severe renal disease or those who are pregnant or breastfeeding. The median dose for MTX therapy is 15 mg/week. Patients should supplement with 1 to 5 mg of folic acid daily to prevent the most common side effect, nausea and diarrhea. Alopecia can occur but it is temporary and reversible. More notable adverse effects include myelosuppression, pulmonary fibrosis and hepatoxicity, especially in diabetics.
PEARL: Advise patients to take folic acid on days they are not taking MTX
Cyclosporine is best used acutely for treatment of erythrodermic psoriasis or severe pustular or plaque psoriasis. The goal is to bridge to long-term biologic therapies. Cyclosporine has good efficacy and patients can achieve 70% clearance in 8-16 weeks at 5 mg/kg/day. The most serious adverse effects of cyclosporine include nephrotoxicity, hypertension, and malignancy (NMSC and lymphoproliferative disorders).
PEARL: Cyclosporine should be tapered, not stopped abruptly.
Acitretin is a systemic retinoid that can be used in moderate plaque psoriasis and palmoplantar psoriasis. It’s helpful in psoriasis patients with a history of NMSC as it may have chemo preventive effects. The most common side effects are xerosis and hair loss. Acitretin is teratogenic and must be avoided in women of childbearing age. Acitretin is also contraindicated in patients with severely impaired liver or kidney function.
Apremilast is approved in plaque psoriasis patients of ALL severities as well as psoriatic arthritis (PsA). This medication is dosed 30 mg twice daily but decreased to 30 mg once daily in patients with severe renal impairment. Overall, apremilast is well tolerate and side effects may include nausea, diarrhea, and weight decrease.
What Biologic to Choose?
The first step is to determine whether the patient has psoriatic arthritis (PsA) or not. PsA may have peripheral and/or axial involvement. The distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints are most likely to be involved in peripheral arthritis, so take a close look at the hands during physical exam.
There are 3 different classes of biologics:
- Tumor necrosis factor or TNF-alpha inhibitors
- IL-17 inhibitors
- IL-23 inhibitors
TNF inhibitors are the best selection in patients with both peripheral and axial PsA. TNF inhibitors should be avoided in patients with demyelinating disease or hepatitis B. TNF inhibitors are not preferred in patients with a history of latent tuberculosis (TB) or advanced congestive heart failure (CHF).
IL-17 inhibitors work quickly, plaque clearance in just a few weeks. IL-17i work well in axial and peripheral PsA. IL-17i should be avoided in patients with a history of inflammatory bowel disease.
IL-23 inhibitors work well in plaque psoriasis and peripheral PsA and requires fewer injections. There is evolving evidence to support efficacy in axial PsA.
PEARL: labs to order for patients initiating biologic therapy
Baseline: CBC, CMP, Hepatitis B&C, HIV at providers discretion
Ongoing: annual TB evaluation
Some patients begin to flare before the next dose of their biologic mediation. This was commonly encountered with secukinumab. Candidates for dose escalation include obese patients and those patients whose initial good response has waned. The general strategy for dose escalation involves more frequent injections, shortening the interval between injections.
SWITCHING: What happens if approved biologic doesn’t work?
PRIMARY FAILURE – A patient who has never responded optimally to a biologic. The recommendation is to wait 6 months and then consider switching to different class of biologic.
SECONDARY FAILURE– If a patient has responded but then lost response. Options include dose escalation or switching within class if it helps to address comorbidities such as PsA, or switching to a different class.
Patients with a history of Malignancy:
- History of internal solid-tumor malignancy in remission for ≥ 5 years
- IL-12/23 has the most safety data, followed by IL-17 and IL-23 inhibitors
- TNF inhibitors data mixed, but generally considered safe as well
- History of liquid tumors regardless of remission status (lymphomas and leukemias), and history of internal solid-tumor malignancy in remission for < 5 years, active liquid or solid internal malignancy
- Avoid biologic medications in general
- History of keratinocyte carcinomas (cutaneous SCC, BCC)
- Use of biologics permissible with regular skin checks
- History of internal solid-tumor malignancy in remission for ≥ 5 years
- Risk factors for reactivation of latent TB: HIV/AIDS, transplantation, TNF-α blockers, close contacts, kidney dialysis
- Risk of reactivation of latent TB is much lower with IL-17 inhibitors and IL-23 inhibitors compared to TNF inhibitors
- Latent TB Treatment: 6- to 9-month regimen with isoniazid monotherapy
Take Home Points
- Move away from a “reactive” treatment approach and adopt a “proactive” treatment approach.
- The median duration to maintain clear or almost clear skin with tapinarof cream is 4 months.
- Consider insurance, comorbidities, and severity when selecting the optimal therapy.
- PsA should be considered when selecting the optimal biologic therapy.
This information was presented by Dr. April Armstrong at the DERM2O22 NP/PA CME conference held July 28-31, 2022. The above highlights from their lecture were written and compiled by Dr. Mojgan Hosseinipour.
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