Treatments for psoriasis and the risk of malignancy

Background

There are multiple therapeutic options for the treatment of moderate to severe psoriasis. The process of choosing among potential treatment options requires both the physician and the patient to weigh the benefits of individual modalities against their potential risks. Traditional systemic therapies for psoriasis, including methotrexate (MTX) and cyclosporine (CsA), have a well-documented array of toxicities, particularly end-organ toxicities. Over the past several years, the use of biologic therapies for the treatment of moderate to severe psoriasis has been a major clinical and research focus. With the advent of these novel immunosuppressive therapies, one of the central safety issues surrounding these agents is their potential to increase the risk of malignancy.

Objective

Our objective was to review the risk of malignancy associated with therapies for moderate to severe psoriasis, including phototherapy, traditional systemic therapies, and biologic therapies. We reviewed the existing body of literature in order to define the known incidence of malignancy associated with psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB), MTX, CsA, mycophenolate mofetil (MMF), and biologic therapies, including alefacept, efalizumab, infliximab, etanercept, adalimumab, and ustekinumab.

Results

PUVA, when given long term, is associated with increased risks of cutaneous squamous cell carcinoma and malignant melanoma. Reviews of studies on UVB, both narrowband and broadband, do not indicate any increased risk of nonmelanoma skin cancer or melanoma. The traditional systemic psoriasis therapies—MTX, CsA, and MMF—may be associated with an increased risk of lymphoproliferative disorders during treatment, demonstrated in clinical trials in patients with rheumatoid arthritis and documented in case reports concerning psoriasis patients. The risk of malignancy with biologic therapy is still unclear. However, the majority of studies examining this carcinogenic risk suggest that tumor necrosis factor–α inhibitors may cause a slightly increased risk of cancer, including nonmelanoma skin cancer and hematologic malignancies.

Limitations

The majority of studies cited in this review lack the power and randomization of large clinical trials, as well as the long-term follow-up periods which would further substantiate the hypothetical link between these antipsoriatic treatment regimens and the potential for malignancy. Because of the substantial lack of clinical data, the majority of studies evaluated focus on the treatment of patients with rheumatoid arthritis, which is a systemic inflammatory disorder comparable to psoriasis. Additionally, the increased risk of malignancy associated with psoriasis itself is a confounding factor.

Conclusion

Many of the therapies for moderate to severe psoriasis, including PUVA, traditional systemic therapies, and some biologic therapies, may increase the risk of malignancy. Appropriate patient counseling and selection, as well as clinical follow-up, are necessary to maximize safety with these agents. Further long-term study is necessary to more precisely quantify the risks associated with biologic therapies.

Introduction

Psoriasis is a relatively common inflammatory disease of the skin and joints, which has been shown to affect approximately 2% of the general population in the United States.¹ While psoriasis can occur at any age, for many clinical symptoms present by early adulthood. Psoriasis can develop into a chronic, debilitating disease which markedly impacts quality of life and contributes significantly to health care costs.² Moderate to severe psoriasis often necessitates life-long alternating systemic therapies in order to alleviate symptoms. In recent years the expanding armamentarium of therapeutic options available to the patient with moderate to severe psoriasis has permitted physicians to more aggressively combat the inflammation central to this disease's pathogenesis. In addition to the long-standing assortment of systemic therapies, such as psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB), methotrexate (MTX), cyclosporine (CsA), and mycophenolate mofetil (MMF), much attention has recently been devoted to the new biological therapies which target T cells and modify immune responses. While several of these therapies have shown promise in effectively controlling psoriasis, there is the potential for systemic toxicity with these therapies related to their immunosuppressive effects, including serious infections and increased risk for malignancy.

The debate as to whether or not these systemic treatments do in fact increase a patient's risk of malignancy remains largely unresolved and has been further confounded by the premise that psoriasis, being a chronic inflammatory disorder comparable to rheumatoid arthritis (RA) or Crohn's disease, may also inherently place the patient at a higher likelihood of developing certain cancers. The pathophysiology of psoriasis involves an abnormal immune activation characterized by the increased activity of T cells, antigen-presenting cells (ie, dendritic cells and Th1 cytokines), and B lymphocytes.3, 4, 5