Dermatology Online Journal

Commentary: Psoriasis patients with a history of malignancy represent an important but overlooked study population
Paul Persad MD¹, Michelle M Levender MD¹, Steven R Feldman MD PhD^1,2,3
Dermatology Online Journal 17 (2): 10

1. Department of Dermatology
2. Department of Pathology
3. Department of Public Health Sciences
Center for Dermatology Research
Wake Forest University School of Medicine, Winston-Salem, North Carolina. mlevende@wfubmc.edu

---

Abstract

The treatment of moderate to severe psoriasis often requires the administration of systemic agents. However, information is limited on the safety of systemic agents in patients with pre-existing cancers. We attempt to summarize the small body of data and urge organized study of this patient population.

---

Psoriasis is rarely perceived as a life-threatening condition. Furthermore, psoriasis is linked to considerable morbidity including cardiovascular disease and lymphoma. The psychological and economic impact of psoriasis on the individual and society is often underestimated. Whereas several traditional treatment strategies are available for limited disease, systemic therapies are often necessary for moderate to severe afflictions. Methotrexate (MTX), cyclosporine (CsA), retinoids, and most recently immunomodulators including tumor necrosis factor (TNF) inhibitors, are part of our arsenal for moderate to severe disease. Treatment protocols for patients with no history of malignancy and for patients with a history of skin cancer are well documented in the literature [1]. For moderate to severe psoriatic patients with comorbid internal malignancy, there are no such treatment protocols. In fact, there has been limited research done on the effect of systemic treatments on patients with pre-existing malignancy and therefore, management of these patients can present a challenge. MTX and CsA increase the likelihood of non-melanoma and melanoma skin cancer, especially after PUVA therapy [2, 3]. The incidence of treatment-related lymphoproliferative disorders is also increased [4]. The risks of the biologic therapies remain largely theoretical, in part because of the well-intentioned reluctance of researchers to include patients with underlying internal malignancies in clinical trials. The rheumatoid arthritis literature case reports and observational studies link TNF inhibitors with lymphoproliferative disorders. In large cohort studies and meta-analyses of clinical trials the data is less convincing [5]. A three fold increased rate of lymphoma in inflammatory bowel disease (IBD) patients treated with TNF-alpha inhibitors was found in a recent meta-analysis [6]. The confounding effects of previous immunomodulator treatment and an elevated baseline lymphoma rate in this population, however, make drawing definitive conclusions difficult.

We sought to evaluate the available evidence for managing moderate to severe psoriasis patients with comorbid internal malignancy. We performed a qualitative review of the dermatology and rheumatology literature looking for all studies that examined systemic treatment modalities in psoriasis patients with pre-existing internal malignancy. Our search revealed only 2 studies that specifically included patients with known malignancy in their study populations. Strangfeld et al. analyzed the recurrence of malignancies in 122 patients with prior history of cancer in 2010, using the German Rheumatoid Arthritis-Observation of Biologic Therapy (RABBIT) registry. Investigators also used a nested case-control design to discern the incidence of new malignancies. They found no significant increase in the incidence of new malignancies or recurrences after approximately 5 years of follow up in patients treated with biologics [7]. In a similar study this year, Dixon et al. used the British Society for Rheumatology Biologics Register data to assess the incidence of recurrence among 177 anti-TNF treated patients and 177 disease modifying anti-rheumatic drugs (DMARDs) treated control patients with histories of internal malignancy. The rate of incident malignancy in the anti-TNF treatment group was 25.3 events per 1,000 person-years after 3 years of follow up. The rate of incident malignancy in the DMARD treated control group was 38.3 events per 1,000 person-years after almost 2 years of follow up [8]. Our search revealed no similar studies in the dermatology literature examining systemic psoriasis therapies in patients with a history of malignancy.

Rigorous studies of long-term safety are a formidable undertaking. Several characteristics in addition to study size are essential to quality data. Adequate duration and completeness of follow up are necessary for detection of uncommon phenomena such as the onset or progression of malignancy. Appropriate controls from demographically comparable populations or large national registries will assist improving external validity. Performing such studies represents a particular challenge in an at-risk patient population such as cancer patients. However, psoriasis and cancer are common conditions and managing psoriasis patients with cancer is a situation that most dermatologists will face. Thus, it is critical that an effort be made to fill this gap in the literature and include, rather than exclude, this patient population in future studies on biologics. In the meantime, treating patients with severe or refractory psoriasis and a history of pre-existing malignancy may sometimes require using these treatments, even though data about their malignancy risk is limited. The potential risks and benefits must be weighed carefully and in these cases, consultation with an oncologist is recommended.

References

1. Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008; 58(5):826-850. [PubMed]

2. Stern RS, Zierler S, Parrish JA. Methotrexate used for psoriasis and the risk of noncutaneous or cutaneous malignancy. Cancer 1982; 50(5):869-872. [PubMed]

3. Cockburn IT, Krupp P. The risk of neoplasms in patients treated with cyclosporine A. J Autoimmun 1989; 2(5):723-731. [PubMed]

4. Kamel OW. Lymphomas during long-term methotrexate therapy. Arch Dermatol 1997; 133(7):903-904. [PubMed]

5. Dommasch E, Gelfand JM. Is there truly a risk of lymphoma from biologic therapies? Dermatol Ther 2009; 22(5):418-430. [PubMed]

6. Lakatos PL, Miheller P. Is There an Increased Risk of Lymphoma and Malignancies Under Anti-TNF Therapy in IBD? Curr Drug Targets 2009. [PubMed]

7. Strangfeld A, Hierse F, Rau R, Burmester GR, Krummel-Lorenz B, Demary W et al. Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT. Arthritis Res Ther 2010; 12(1):R5. [PubMed]

8. Dixon WG, Watson KD, Lunt M, Mercer LK, Hyrich KL, Symmons DP. Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register. Arthritis Care Res (Hoboken ) 2010; 62(6):755-763. [PubMed]

© 2011 Dermatology Online Journal