Combination Therapy of Biologics With Traditional Agents in Psoriasis

Lyn C. Guenther, MD, FRCPC

Disclosures

Skin Therapy Letter. 2011;16(6) 

In This Article

Combination Therapy With Alefacept (Amevive®)

Alefacept has Health Canada approval for use in combination with mid- to high-potency topical agents, ultraviolet B (UVB) phototherapy, methotrexate, cyclosporine, and systemic retinoids.[14] The Canadian AWARE study showed that alefacept allowed for a reduction in dosage or discontinuation of concomitant systemic agents or phototherapy.[15]

In an open-label study of 1–3 courses of alefacept (n=449), combination therapy with topical agents occurred in approximately one-third and combination treatment with phototherapy or traditional systemic agents was also used in approximately one-third of patients [UVB (n=24), methotrexate (n=63), cyclosporine (n=42), systemic retinoids (n=23), and prednisone (n=7)].[16] When alefacept was added to existing treatment regimens, ≥30% achieved a response of mild or better. Concurrent therapy with methotrexate or cyclosporine resulted in lower response rates than with other agents. A physician global improvement (PGA) of at least two categories was achieved by 20–21% on methotrexate, 31–43% on cyclosporine, 50–64% on systemic retinoids, 43–62% on mid- to high-potency topical agents, and 55–77% on UVB. There was no increased risk of infection or malignancy when alefacept was used in combination with methotrexate or cyclosporine. The lower response rates with methotrexate combination therapy may be secondary to the study requirement for discontinuation of methotrexate within 4 weeks of initiation of alefacept and the fact that many patients experienced flares as soon as it was discontinued. Cyclosporine was also initially suspended within the first 4 weeks of alefacept therapy; however, due to flares, the protocol was amended so that cyclosporine could be discontinued within 6 weeks after the 12-week alefacept dosing period. Other therapies could be continued throughout the treatment courses.

UVB Phototherapy

In an open label study of 60 patients, greater efficacy and a more rapid onset of action were noted with a combination of alefacept and narrowband (nb) or broadband (bb) UVB compared with alefacept monotherapy.[17] Four weeks after treatment was started, PASI 50 was achieved at the US site in 0% on monotherapy vs. 22% on bb UVB + alefacept, and at the French site 44% on monotherapy vs. 82–90% on nb UVB + alefacept. Similarly in a half-side comparison alefacept/nb UVB study (n=14), the side treated with nb UVB had accelerated and improved clearance.[18]

Acitretin

A case series of two patients who had previously been unresponsive to ultraviolet phototherapy, methotrexate, and acitretin showed that combination therapy of alefacept with low dose (10 mg, 25 mg) acitretin shortened the onset of improvement to 4–5 weeks (compared with the usual 8 weeks) and improved inverse and palmoplantar psoriasis.[19] In one patient with a history of squamous cell carcinoma (SCC) who developed three SCCs every 2 weeks while on etanercept monotherapy, after acitretin 25 mg every other day was added only actinic keratoses developed during the 18 month follow-up.[20]

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