Combination Therapy of Biologics With Traditional Agents in Psoriasis

Lyn C. Guenther, MD, FRCPC


Skin Therapy Letter. 2011;16(6) 

In This Article

Abstract and Introduction


Although biologics are very efficacious as monotherapy in patients with psoriasis, combination treatment with traditional systemic and topical therapies may increase the speed of onset and enhance efficacy without significant additional toxicity. In contrast, in psoriatic arthritis, the addition of methotrexate to anti-tumour necrosis factor-alpha therapy does not enhance efficacy in either the skin or joints.


Psoriasis is a chronic inflammatory disorder that is associated with a number of comorbidities including arthritis, cardiovascular risk factors, and inflammatory bowel disease.[1] Patients with moderate to severe disease usually require phototherapy, traditional systemic medications (e.g. methotrexate, acitretin, and cyclosporine), or biologic agents (e.g., adalimumab, alefacept, etanercept, infliximab, and ustekinumab) for adequate control.[2] Alefacept binds to CD2 on CD45RO+ effector T lymphocytes, inhibiting their activation and inducing apoptosis of these T cells, while adalimumab, etanercept, and infliximab inhibit tumour necrosis alpha, a cytokine that is elevated in patients with psoriasis, and ustekinumab inhibits interleukins 12 and 23, which are also elevated in psoriasis.[3] Although biologics are generally used as monotherapy, in Europe the concurrent use of traditional systemic agents can be found in up to 30% of cases.[4] Addition of a biologic to traditional systemic therapy can enhance efficacy, or permit discontinuation or dose reduction of the traditional systemic agent without compromising disease control. On the other hand, addition of a systemic agent, phototherapy, or topical therapy to a biologic can enhance efficacy, including speed of onset, degree of clearing, and in some cases duration of remission or improve safety. Since acitretin can suppress the development of skin cancers, such as squamous cell carcinoma in high risk patients,[5] addition to at-risk individuals receiving biologic treatment might enhance safety.

In rheumatoid arthritis (RA) and psoriatic arthritis patients, methotrexate is routinely used with tumour necrosis factor-alpha (TNF-alpha) inhibitors without additional toxicity.[6,7] In contrast to the psoriasis and RA investigations, studies in patients with psoriatic arthritis have shown that concurrent methotrexate and anti-TNF agents (adalimumab,[8] etanercept,[9] infliximab[10]) does not enhance efficacy in either the skin or joints. Some efficacy and safety data in psoriasis are available for combination therapy with adalimumab, alefacept, etanercept, and infliximab, but not for ustekinumab.


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