Secukinumab and Apremilast Combination Therapy for Recalcitrant Psoriasis

Introduction

Psoriasis is a chronic inflammatory disease of the skin and joints that is associated with significant morbidity if left untreated, such as increased risk of cardiovascular events and mental illness. Treatment options range from topical agents such as corticosteroids and calcineurin inhibitors for milder disease to injectable biologic agents for moderate to severe disease or psoriatic arthritis.

Case Report

A 61-year-old woman presented with a 1-year history of arthritis of the left knee and right ankle to an outside rheumatologist and was diagnosed with psoriatic arthritis, for which she was initiated on adalimumab at a dose of 40 mg subcutaneously every two weeks. She subsequently developed pruritic, well-demarcated, erythematous plaques of the bilateral palms and soles as well as her legs, which were consistent with a diagnosis of plaque psoriasis. The plaques on the soles of her feet led to considerable pain upon ambulation. After a lack of improvement on adalimumab, the drug was discontinued and the patient was initiated on ustekinumab at a dose of 45 mg subcutaneously at week 0, week 4, and every 12 weeks subsequently. After she had no improvement on ustekinumab, it was discontinued and treatment was initiated with infliximab and methotrexate 17.5 mg weekly, which she continued for 10 months with no improvement.

She then began treatment with secukinumab, which led to significant improvement of her arthritis, but only a modest effect on her skin lesions. Apremilast was added to her secukinumab regimen at a dose of 30 mg twice daily, leading to significant improvement in both her psoriasis and her psoriatic arthritis. Her current regimen is secukinumab at a dose of 300 mg monthly with apremilast 30 mg twice daily. She has tolerated this combination well with no adverse events noted.

Discussion

Psoriasis is a common inflammatory condition which can affect the skin and joints and affects more than 2% of the U.S. population. ¹ The most common skin manifestation of psoriasis is well-demarcated, erythematous, scaly plaques affecting the extensor surfaces of the extremities or the scalp; however, it also can be seen anywhere on the skin, including the back, abdomen, genitals, and the non-extensor extremities. ² Other skin manifestations include pustular psoriasis, which presents as pustules on an erythematous base; inverse psoriasis, which affects flexural surfaces; and guttate psoriasis, which presents as nummular plaques classically in children, but in adults as well. ³ Psoriasis can progress to erythrodermic psoriasis, which is directly associated with significant morbidity and mortality as the compromise of the protective skin barrier can easily lead to sepsis. ⁴

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Figure 1

Patient's left foot prior to initiation of combination therapy of apremilast and secukinumab

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Figure 2

Patient's left foot 3 weeks after initiation of combination therapy of apremilast and secukinumab

Psoriatic arthritis is another possible complication and can affect any joint, but is seen most commonly in the fingers. The inflammation from psoriasis also has been shown to be associated with an increased risk of coronary artery disease and metabolic syndrome, highlighting the systemic effects of this disease. ⁵

There are a variety of biologic treatment options available for the treatment of psoriasis. These include adalimumab, etanercept, infliximab, secukinumab, ixekizumab, and ustekinumab. These agents target various chemokines implicated in the pathogenesis of psoriasis, such as TNF-alpha, IL-17a, IL-12, and IL-23. ⁶ Apremilast, a phosphodiesterase 4 inhibitor, also has been shown to be effective in moderate to severe psoriasis in two phase 3 clinical trials (ESTEEM-1 and ESTEEM-2). ⁷ It has the added benefits of being an oral therapy and not having the same risk of immunosuppression as seen in some of the biologic agents. Combination therapies of agents such as methotrexate and cyclosporine with a biologic or NB-UVB therapy have been shown to be efficacious in the treatment of psoriasis refractory to monotherapy. ⁸ In a retrospective review of chronic plaque psoriasis patients using apremilast with another agent, AbuHilal et al. showed that apremilast is efficacious in combination therapy with NB-UVB, methotrexate, acitretin, cyclosporine, etanercept, adalimumab, infliximab, or ustekinumab. ⁸

However, the combination of apremilast with secukinumab was not reported in this study. Rothstein et al. reported the first case of recalcitrant psoriasis with psoriatic arthritis treated successfully with apremilast and secukinumab. ⁹ Like our case, this patient was refractory to multiple topical and systemic agents, including adalimumab, infliximab, and ustekinumab, and achieved near total clearance with the combination of apremilast and secukinumab. Combined with the previously published report of this combination, our case suggests that combination therapy with apremilast and secukinumab may be a promising option for the treatment of refractory psoriasis.