Nonmelanoma skin cancer increased in RA patients

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Nonmelanoma skin cancer increased in RA patients

Rheumawire

Dec 19, 2005

Zosia Chustecka

Wichita, KS - Rheumatoid arthritis (RA) patients are known to be at an

increased risk of developing lymphoproliferative disorders, particularly

non-Hodgkin's lymphoma. Now a large US study suggests that they may

also be

at an increased risk of developing nonmelanoma skin cancer, such as

basal

cell carcinoma and squamous cell carcinoma [1].

The results come from an analysis of data collected by the National Data

Bank for Rheumatic Diseases, directed by Dr Frederick Wolfe

(University of

Kansas, Wichita), and are reported in the November 2005 issue of the

Journal

of Rheumatology.

The researchers compared data collected since 1999 on 15 789 patients

with

RA and 3639 patients with osteoarthritis (OA). Although the crude

incidence

rates were similar for both populations, after adjustment for

covariates,

there was a small but significant increased hazard of developing

nonmelanoma

skin cancer in patients with RA compared with those with OA (hazard

ratio

---

=1.19, p=0.042).

Among the RA patients, the development of nonmelanoma skin cancer was

associated with use of prednisone (HR=1.28, p=0.014) and with the use

of TNF

inhibitors with concomitant methotrexate (HR=1.97, p=0.001). No

association

was found with the use of methotrexate alone (HR=1.12, p=0.471) or

leflunomide (HR=0.83, p=0.173). The researchers comment that the use

of any

TNF inhibitor (adalimumab, etanercept, or infliximab) was associated

with a

slightly increased risk (HR=1.24, p=0.89), but this did not reach

statistical significance, whereas the use of a TNF inhibitor with

concomitant methotrexate raised the risk twofold and was significant.

" This suggests that increasing immunosuppression, particularly with

the use

of TNF inhibitors, may be associated with increased risk for developing

nonmelanoma skin cancer, " the authors write. " However, it is possible

that

the trend toward increased hazard of nonmelanoma skin cancer with

increased

immunosuppressive medications is actually confounding by indication: a

function of the severity of the underlying RA rather than the direct

effects

of immunosuppression itself. "

" Together, these findings suggest that skin-cancer screening at regular

intervals may be warranted for all patients with RA, especially those

receiving chronic immunosuppressive therapy, " the researchers conclude.

Findings " in concert " with European studies

The finding of an increased risk of nonmelanoma skin cancer in RA

patients

from this study is " in concert " with earlier studies from Europe, the

researchers comment. They note that two studies from Northern Europe

have

also suggested an increased risk: they compared the incidence in RA

patients

with that in the general population and found relative risks ranging

from

1.17 [2] to 1.4 [3]. There have also been several case reports of a

rapid

development of squamous cell carcinoma after administration of TNF

inhibitors [4, 5], the authors note, but a study of patients in clinical

trials with etanercept found no increase in squamous cell carcinoma

compared

with the general population [6].

" Basal cell carcinoma and squamous cell carcinoma are among the

commonest

types of malignancies, and although they rarely metastasize to

distant sites

or lead to death, their high prevalence and associated morbidity

contribute

to the overall public-health burden, " the authors comment.

Sources

1. Chakravarty EF, Michaud K, Wolfe F. Skin cancer,

rheumatoid arthritis and tumor necrosis factor inhibitors. J

Rheumatol 2005;

32:2130- 2135.

2. Gridley G, McLaughlin JK, Ekbom A, et al. Incidence of

cancer among patients with rheumatoid arthritis. J Natl Cancer Inst

1993;

85:307-311.

3. Mellemkjaer L, Linet MS, Gridley G, et al. Rheumatoid

arthritis and cancer risk. Eur J Cancer 1996; 32A:1753-1757.

4. KJ, Skelton HG. Rapid onset of cutaneous squamous

cell carcinoma in patients with rheumatoid arthritis after starting

tumor

necrosis factor receptor IgG1-Fx fusion complex therapy. J Am Acad

Dermatol

2001; 45:953-956.

5. Esser AC, Abril A, Fayne S, et al. Acute development of

multiple keratoacanthomas and squamous cell carcinomas after

treatment with

infliximab. J Am Acad Dermatol 2004; 50 (Suppl 5):S75-S77.

6. Lebwohl M, Kim D, Do T, et al. Cutaneous squamous cell

carcinoma incidence is not increased in rheumatoid arthritis patients

receiving etanercept. EULAR 2003; June 12-15 2003; Lisbon, Portugal.

Available at: http://www.eular.org.