Apremilast and Secukinumab Combined Therapy in a Patient With Recalcitrant Plaque Psoriasis

We report a 67-year-old Caucasian man with a many year history of severe recalcitrant plaque psoriasis and psoriatic arthritis who achieved near complete clinical clearance on a combination of apremilast and secukinumab. Upon presentation the patient had diffuse pink papules and plaques with minimal scale involving a body surface area of 80%. The patient had previously failed topical, light, oral, subcutaneous, and intravenous treatments including ustekinumab, infliximab, adalimumab, acitretin, and cyclosporine. Although disease improvement was achieved on etanercept, response was lost after several years.

Treatment with secukinumab 300 mg every month was initiated in June 2015, but disease response began to decrease approximately 6 months later. In November 2015 apremilast was added and up-titrated to 30 mg twice daily along with a 3-month 10 mg prednisone taper, which was completed without disease rebound. His current regimen includes apremilast 30 mg twice daily in addition to secukinumab 300 mg every month. After three months of combination therapy, the patient’s disease has stabilized with only a few scattered erythematous mildly scaly plaques on his bilateral extremities and trunk, and his quality of life has significantly improved (see Figures 1 and 2). His affected body surface area at this last visit was 5% and his physician global assessment of disease was rated a score of 1. His only side effect was mild diarrhea and he denied weight loss or depression. Laboratory work-up was within normal limits aside from a mildly elevated white blood cell count at the end of his prednisone course.

Although multiple, highly efficacious treatments are available for moderate-to-severe psoriasis, patients with contraindications or severely refractory disease present therapeutic challenges without a consensus algorithm to guide drug selections. Apremilast is an oral phosphodiesterase 4 (PDE4) inhibitor that offers an alternative side effect profile, easier administration given its oral use, and decreased cost compared to biologic agents. Its efficacy has been demonstrated in two pivotal phase three clinical trials (ESTEEM-1 and ESTEEM-2) in moderate-to-severe psoriasis,^1,2 and is linked to a reduction in keratinocyte proliferation and psoriatic plaque development.³ Apremilast monotherapy, however, demonstrates lower clinical efficacy than biologic monotherapy. While apremilast provides a 75% improvement in psoriasis area and severity index (PASI-75) in approximately 30% of patients,^1,2 the majority of biologic agents enable this level of skin clearance in greater than 70% of patients.^4-8

Combination therapy in which biologic therapy is added to a traditional systemic agent such as methotrexate can provide greater disease control compared to biologic monotherapy,^9.10 and is a treatment strategy currently implemented in up to 30% of patients on TNFα-inhibitors.^11,12 Combination therapy with apremilast has been reported in a case report with adalimumab,¹³ and in a retrospective analysis of 81 patients on various anti-psoriatic agents including narrow band UVB therapy, methotrexate, acitretin, cyclosporine, etanercept, adalimumab, infliximab, or ustekinumab.¹⁴ The present case is the first reported of apremilast and secukinumab combination therapy for the treatment of plaque psoriasis, which lead to significant disease improvement with minimal side effects and no laboratory abnormalities. This case, consistent with the findings of the two previously published articles on apremilast combination therapy, warrants further investigation of apremilast combination therapy particularly for cases of severely recalcitrant psoriasis with limited treatment alternatives.