PSORIASIS, SYSTEMIC TREATMENT

By Gary M. White, MD


Categories of Biologic Agents for Psoriasis

Efficacy in Psoriasis, PASI 75 wk 12-24

Drug PASI-75 at week 12-24
Guselkumab 91%
Ixekizumab 90%
Brodalumab 86%
Secukinumab 82%
Ustekinumab 80%
Adalimumab 77%
Narrow Band UVB 60-70%
Methotrexate 60-70%
Tofacitinib 59%
Etanercept 50%
Apremilast 33%

Obesity

Psoriasis and obesity are highly associated. For example, various studies have shown that obesity preceded psoriasis in both children and adults [JAMA Derm may 2014 150:573]. Furthermore, even small reductions in weight can greatly improve psoriasis [JAAD 2014;71;839].

Infliximab and ustekinumab dosing are weight dependent so they may be preferred in obese patients. In contrast, the efficacy of etanercept and adalimumab are lessened in obese patients. Ixekizumab and secukinumab are so effective that they still do well in obese patients. Apremilast's efficacy is only moderate, but it does as well in obese patients as trim patients (and it may help them use weight). Methotrexate is not preferred in obese patients as obesity is a risk factor for fibrosis/cirrhosis in patients on methotrexate.

Infection

Drug Cumulative incidence rate of serious infection
Ustekinumab .83
nonmethotretrate, nonbiologic 1.05
Methotrexate 1.28
Etanercept 1.47
Adalimumab 1.97
Infliximab 2.49

Malignancy

Long-term treatment with one of the TNF inhibitors (etanercept, adalimumab or infliximab) increases the risk for malignancy (excluding non-melanoma skin cancer) in patients with psoriasis. Methotrexate and ustekinumab do not [JAAD 2017;77;845].

Depression

Patients with psoriasis are more likely to be depressed (comorbidity). Any therapy that improves the psoriasis can lessen any depression. One study showed that, compared with conventional therapy (UVB, PUVA, methotrexate, cyclosporine, systemic corticosteroids, fumarates, mycophenolate mofetil, and oral retinoids), biologics (etanercept, adalimumab, infliximab, and ustekinumab) were associated with a lower incidence of depressive symptoms [JAAD 2018;78;70–80]. Apremilast and brodalumab should be avoided in patients with depression as they increase risk.

Pregnancy

There is an independent increased risk of preterm birth in pregnant women with psoriasis. Acitretin and methotrexate are contraindicated in pregnancy. Apremilast and cyclosporin are relatively contraindicated. The biologic agents are in general pregnancy category B.

Children

In children with psoriasis, there is support and data for adalimumab (>= 4 years), etanercept (>= 6 years) and ustekinumab (>= 12 years).

Demyelinating Diseases

Patients with demyelinating diseases (DD) (e.g. multiple sclerosis, optic neuritis, acute transverse myelitis) should avoid the anti-TNF agents. Those with a first degree relative with a DD should probably avoid them as well.

UVB

Narrow band UVB is not as effective as the TNF agents, but does not have systemic side effects. PASI-75 varies widely in studies [Am J Clin Dermatol. 2013 Apr;14(2):87-109], but may be in the 60-70% range. It is an excellent choice for patients who want to avoid potential systemic side effects and do not have a history of skin cancer. Children with psoriasis may be treated as well. It is a good choice for pregnant women, but they may need supplementation with folic acid.

Ixekizumab

Ixekizumab is highly efficacious for psoriasis. It has been shown to be superior to ustekinumab [BJD 2017;177;1014].

Adalimumab

Adalimuab is very effective for psoriasis. It is a shot given 2/month.

Ustekinumab

Ustekinuimab is highly effective for psoriasis. A shot given every 3 months. Ustekinumab appears to be an effective treatment for adolescents age 12 and older with moderate to severe psoriasis [J Am Acad Dermatol 2015 Aug 07 ahead of print].

Secukinumab

Secukinumab is given 300 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2 and 3 followed by monthly maintenance dosing starting at week 4. It is also effective for psoriatic arthritis. In a head-to-head study against ustekinumab, secukinumab was superior [JAAD 2017;76;60].

Etanercept

Etanercept is the least effective of the TNF agents. It is given 2/week x 3 months, then once per week. Efficacy may decrease at the 3 month step-down.

Methotrexate

Methotrexate is effective for psoriasis and has been used for decades. However, it is not as effective as the TNF agents, has potential liver toxicity and patients need to limit alcohol consumption. Periodic monitoring of the liver is mandatory during therapy. In July 2014, the FDA approved Rasuvo™, a subcutaneous injectable methotrexate therapy delivered in an auto-injector for the treatment of psoriasis and several other conditions.

Apremilast

Apremilast is FDA approved for moderate to severe psoriasis as well as psoriatic arthritis. Common side effects include diarrhea, headache and nausea. There is no laboratory monitoring, alcohol consumption restrictions, category X classification, or immunosuppressive infection or cancer risk. Efficacy is relatively low with PASI-75 in 30% of patients at 4 months [J Am Acad Dermatol. 2014;70(suppl 1):AB164]. Weight loss of more than 5% may occur in about 20% of patients.

Acitretin

Acitretin is an older drug and an alternative when other agents not viable. The key advantage is that it is not immunosuppressive.

Cyclosporin

Cyclosporin for psoriasis is usually given 2-5 mg/kg/day. Renal toxicity, risk for infection and hypertension are all potentially serious side effects. Short, intermittent therapy is the preferred treatment for healthy adults. The AAD recommends a maxiumum of 1 year of continuous treatment unless their are no good alternatives.

Systemic Steroids

Systemic steroids are not traditionally used for psoriasis because of there long term complications and the anecdotal concern about creating a pustular flare/worsening of the severity of the psoriasis. However, this latter possibility is not well-documented and indeed many clinicians will occasionally use SS for psoriasis.

Combining Systemic Therapies

The medical board of the National Psoriasis Foundation recommends that combining systemic therapies can result in greater efficacy while minimizing toxicity [JAMA Derm 2015;151;432]. Their preferred order of combination is first a biologic with methotrexate, then a biologic and acitretin and finally a biologic with phototherapy.

If One Biologic fails?

Studies have shown that if a patient fails 1 anti-TNF agent, s/he is still likely to respond well to another biologic agent [JAAD 2016;74;176]. Using PASI-75 as a standard, patients are 60-68% likely to respond if rotated to etanercept, adalimumab or ustekinumab.

What if Psoriasis develops during Biologic Therapy

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