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ANTI-TNF THERAPIES MAY INCREASE MALIGNANT MELANOMA RISKS IN PEOPLE WITH RHEUMATOID ARTHRITIS

CHICAGO - According to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Chicago, people taking anti-tumor necrosis factor therapies to treat rheumatoid arthritis have a higher risk of developing malignant melanoma.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Anti-TNF therapies suppress the immune system and taking these medications can increase the risk of developing infections. Additionally, recent research has reported a possible connection between the use of anti-TNF therapy and certain skin cancers including malignant melanoma. Researchers from Sweden recently reviewed data to investigate the risk of malignant melanoma in patients with RA compared to the general population, and to investigate whether anti-TNF treatment such as adalimumab (Humira®), etanercept (Enbrel®) and infliximab (Remicade®) elevates malignant melanoma risk in rheumatoid arthritis.

“Anti-TNF therapies are excellent drugs that have a major impact on the health and well-being of patients with rheumatoid arthritis,” says investigator, Julia Fridman Simard, ScD; assistant professor at the Clinical Epidemiology Unit, Department of Medicine at the Karolinska Institutet. “Many patients are treated with these therapies, not just in rheumatoid arthritis, and it is important to understand the potential side effects to inform treatment decisions and clinical practice.”

Using information from the Swedish Biologics Register, ARTIS, linked to other national Swedish registers, the researchers identified 56,336 individuals with rheumatoid arthritis − of which 8,453 were noted as starting anti-TNF therapy, as well as reference subjects from the general population. The risks of getting a malignant melanoma or any other cancer were compared between RA patients and the general population, and between RA patients treated, and not treated, with anti-TNF therapies.

During the study, researchers recorded 32 cases of malignant melanoma among the 8,453 patients with rheumatoid arthritis taking anti-TNF therapies, and 135 cases in the 47,883 patients not taking these therapies. Compared to the general population subjects, individuals with RA were not at increased risk of malignant melanoma. Within the group of patients with RA, the risk of malignant melanoma was approximately 80 percent higher among those patients receiving anti-TNF therapy compared to those patients not receiving these drugs. Malignant melanomas accounted for around seven percent of all incident cancers among the patients with RA. In contrast to the elevated risk of malignant melanomas among patients with RA treated with anti-TNF therapy, there was no increase in the risk for all other types of cancers combined in this group.

Dr. Simard further comments, “Although these findings shed some light on the safety of anti-TNF therapy and its role in the development of malignant melanomas, it should be kept in mind that malignant melanomas accounted for only 7 percent of all cancers in our population, that the overall burden of cancers in patients treated with anti-TNF therapy does not seem to be elevated, and that the absolute risk of an individual patient to develop a malignant melanoma is small. The ‘number needed to treat’ with anti-TNF therapy during one year for one additional malignant melanoma to occur is on the order of several thousands.” She also adds, “from a clinical perspective, our findings suggest we should not forget to pay attention to skin lesions suspicious of melanomas occurring in patients treated with anti-TNF therapy, especially since the prognosis following prompt removal of early melanomas is excellent. Furthermore, more studies to identify patients at high risk are needed to help inform clinical decision making.”

TNF-antagonists (anti-TNF therapy; among drugs called biologics) are a class of drugs that have been used since 1998. Overall, they have been given to more than 600,000 people worldwide. These drugs are given to lessen inflammation by interfering with biologic substances that cause or worsen inflammation.

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education. Follow the meeting on Twitter by using the official hashtag: #ACR2011.

Editor’s Notes: Julia Simard, ScD, will present this research during the ACR Annual Scientific Meeting at McCormick Place Chicago at 4:30 pm on Tuesday, November 8 in Room W375a. Dr. Simard will be available for media questions and briefing at 1:30 pm on Monday, November 7 in the on-site press conference room, W 175C.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover the ACR’s Simple Tasks campaign, which highlights the severity of rheumatic diseases and the importance of early and appropriate referral to a rheumatologist.


Presentation Number: 2523

RA, Anti-TNF Therapy, and Risk of Malignant Melanoma-a Nationwide Population-Based Study From Sweden

Julia F. Simard, (Clinical Epidemiology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden)
Pauline Raaschou, (Clinical Pharmacology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden)
Martin Neovius, (Clinical Epidemiology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden)
Marie Holmqvist,(Clinical Epidemiology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden)
Jonas Eriksson, (Clinical Epidemiology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden)
Johan Askling, (Clinical Epidemiology Unit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden)

Background/Purpose:  States of immune suppression, such as post-transplant therapy, have recently emerged as a possible risk factor not only for non-melanoma skin cancer but also for malignant melanoma (Vajdic CM et al, JAMA 2006). An increased risk of melanoma associated with anti-TNF therapy has been reported (Wolfe F et al, Arthritis Rheum. 2007; Askling J. EULAR Conference Abstract 2009). We aimed to investigate the risk of malignant melanoma in patients with RA compared to the general population, and to investigate whether anti-TNF treatment influences melanoma risk in RA.

Method: A nationwide and population-based cohort of patients with RA were identified using data from the Swedish outpatient register from 2001 through 2009 (n=56,336). Patients starting anti-TNF therapy were identified through linkage to the Swedish Biologics Register ARTIS and to the national Prescribed Drug Register (n=8,453) To each RA patient, 5 general population comparators were matched for sex, year of birth and county of residence. Occurrence of first-ever invasive malignant melanoma, as well as occurrence of first-ever cancer, irrespective of type (all-site), was assessed through linkage to the national Swedish Cancer Register. Relative risks (RRs) for malignant melanoma and all-site cancer were calculated using Cox regression with age as time-scale and anti-TNF therapy treated as a time-dependent variable, adjusted for selected co-morbidities. RRs were assessed overall and by time since start of anti-TNF therapy.

Result: Based on 135 incident melanomas during 253,572 person-years of follow-up among biologics-naí¯ve patients with RA vs. 718 melanomas during 1,460,120 person-years of follow-up in the general population comparator, the RR for malignant melanoma in biologics-naí¯ve patients with RA was 1.1 (95% CI 0.9-1.3). Based on 32 incident malignant melanomas during 44,858 person-years of follow-up from start of anti-TNF therapy, compared to biologics-naí¯ve RA patients, the RR was 1.8 (95% CI 1.2-2.7). Based on 418 incident all site cancers during 42,418 person-years of follow-up among the anti-TNF exposed, the RR was 1.0 (0.9-1.1) compared to biologics-naí¯ve RA patients (Table). Sensitivity analyses also including in situ melanomas resulted in a relative risk of 1.5 (95% CI 1.1-2.1).

Conclusion: In the absence of anti-TNF therapies, RA patients are not at elevated risk of malignant melanoma. Patients selected for and treated with anti-TNF have a higher risk of malignant melanoma than biologics-naí¯ve RA patients. 

Table.  Relative risks adjusted for age, sex and co-morbidities (95% confidence intervals) and number of cases among patients treated with anti-TNF, comparing Swedish patients with RA treated with anti-TNF (n=8,453) to biologics-naí¯ve patients with RA (n=47,883).

 

Anti-TNF-exposed vs. Biologics-naí¯ve RA

Time since first anti-TNF treatment start

 

Overall

< 1 year

1-2 years

≥2 years

Melanoma   Relative risk (95%CI), Cases 

1.8 (1.2-2.7), 32

1.5 (0.6-4.1), 4

2.9 (1.4-5.9), 8

1.7 (1.0-2.7), 20

All-Site Cancer Relative risk (95%CI), Cases 

1.0 (0.9-1.1), 418

1.0 (0.8-1.3), 74

0.9 (0.7-1.2), 63

1.1 (1.0-1.3), 281

Disclosures:
P. Raaschou, None.
J. F. Simard, None.
M. Neovius, None.
M. Holmqvist, None.
J. Eriksson, None. J. Askling, Pfizer Inc, Bristol Meyer Squibb

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