Risk of skin cancer in the drug treatment of rheumatoid arthritis.

Stanford University School of Medicine, Division of Immunology and Rheumatology, 1000 Welch Road, Suite 203, Palo Alto, Stanford, CA 94304, USA.
Expert Opinion on Drug Safety (Impact Factor: 2.74). 10/2008; 7(5):539-46. DOI: 10.1517/14740338.7.5.539
Source: PubMed

ABSTRACT It is well established that rheumatoid arthritis (RA) is associated with an increased risk of lymphoproliferative disorders when compared to the general population. It remains unclear whether this risk is owing to underlying inflammation and immune dysregulation, effects of disease modifying medications or a combination of the two. With increasing use of targeted biologic therapies, including those that may theoretically interfere with innate tumor surveillance, there is increasing concern about the development of other malignancies.
The English language literature was searched to identify observational studies and clinical trials reporting incidence and relative risk of melanoma and non-melanoma skin cancer (NMSC) among RA patients.
The numbers of melanomas reported were too small to draw conclusions regarding increased or decreased risk with underlying RA or commonly used medications. Relative incidence of NMSCs is difficult to assess given the lack of standardized reporting in the general population. No safety signal concerning skin cancer with RA or its therapies is at present identified.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Rituximab is an anti-CD20 monoclonal antibody increasingly used in haematology and rheumatology, but also in internal medicine and dermatology. It has a good tolerance profile without known increased risk of cancer. We report a case of nodular melanoma with a 4.8 mm Breslow thickness that appeared after 2 years of rituximab in a 45-year-old patient with non-Hodgkin lymphoma. Fifteen additional rituximab-associated melanoma cases in 13 patients have been identified in the literature and in the EudraVigilance database. These patients were treated for various indications and had melanomas, often aggressive, initially diagnosed at a metastatic stage in 31% of cases. Our work raises the question of rituximab accountability in melanoma onset in these immunosuppressed patients. A dermatological monitoring seems necessary in patients treated with rituximab, especially in case of risk factors for melanoma. In case of individual melanoma history, the benefit/risk ratio of initiating rituximab therapy should be carefully assessed. © 2013 S. Karger AG, Basel.
    Dermatology 01/2013; 226(3):274-8. DOI:10.1159/000350681 · 1.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A few pitfalls associated with the Anfinsen’s thermodynamic hypothesis are discussed. The most profound one is the misinterpretation of the Anfinsen ‘thermodynamic hypothesis’ in terms of the Second Law of Thermodynamics. This misinterpretation has inspired many scientists to search for a global-minimum in the Gibbs energy as a function of the conformation of the protein, sometimes referred to as the Gibbs energy landscape. Such a minimum in the Gibbs energy is different from the minimum required by the Second Law of Thermodynamics.
    Chemical Physics Letters 07/2011; 511(1):126-128. DOI:10.1016/j.cplett.2011.05.049 · 1.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the potential association between tumour necrosis factor (TNF) inhibitor treatment and malignant melanomas in rheumatoid arthritis, melanoma risks in rheumatoid arthritis patients not treated with biological drugs, and risk of all site cancer with TNF inhibitors as used in rheumatoid arthritis. Population based cohort study. Prospectively recorded data from national clinical, health, and demographic registers in Sweden 2001-10. Patients with rheumatoid arthritis treated (n=10 878) or not (n=42 198) with TNF inhibitors and matched general population comparators (n=162 743). The primary outcome was first invasive melanoma in people without any history of invasive cancer of any type. Hazard ratios were estimated using Cox regression, comparing non-biological drug treated rheumatoid arthritis patients with the general population comparator and TNF inhibitor treated rheumatoid arthritis patients with those not treated with biological drugs. Secondary outcomes included in situ melanomas, second primary melanomas, and all site cancer. 113 first invasive melanomas occurred in rheumatoid arthritis patients not treated with biological drugs, and 393 occurred in the general population comparator cohort. Rheumatoid arthritis patients not treated with biological drugs were not at significantly increased risk of melanoma compared with the general population (hazard ratio 1.2, 95% confidence interval 0.9 to 1.5). 38 first invasive melanomas occurred in rheumatoid arthritis patients treated with TNF inhibitors; these patients had an increased risk of melanoma compared with rheumatoid arthritis patients not treated with biological drugs (hazard ratio 1.5, 1.0 to 2.2; 20 additional cases per 100 000 person years). The risk of a second primary melanoma was non-significantly increased (hazard ratio 3.2, 0.8 to 13.1; n=3 v 10) in rheumatoid arthritis patients treated with TNF inhibitors compared with those not treated with biological drugs. Overall, patients with rheumatoid arthritis who have not been treated with biological drugs are not at increased risk of invasive melanoma compared with the general population. Rheumatoid arthritis patients selected for TNF inhibitor treatment are not at increased overall risk for cancer but have a 50% increased relative risk of invasive melanoma. Given the small increase in absolute risk, these finding may not markedly shift the overall risk-benefit balance of TNF inhibitors as used in clinical practice but might do so in patients at high risk of melanoma for other reasons.
    BMJ (online) 04/2013; 346:f1939. DOI:10.1136/bmj.f1939 · 16.38 Impact Factor