Anti–tumor necrosis factor therapy and cancer risk in patients with autoimmune disorders

Onel, Karen; Onel, Kenan

doi:10.1002/acr.20228

Cited by 19 publications

(12 citation statements)

References 47 publications

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“…Tumor necrosis factor α (TNFα) inhibitors have been shown to be highly effective in the treatment of juvenile idiopathic arthritis (JIA) (1–7). However, questions persist about a possible increased risk of malignancy associated with their use (8), including reports of lymphoma among children with JIA who were treated with TNF inhibitors (9, 10). In 2009, the US Food and Drug Administration (FDA) placed a “black box warning” on TNF inhibitors concerning the risk of malignancy in children, based on an analysis of spontaneous reports to the Adverse Event Reporting System (AERS) (11).…”

mentioning

confidence: 99%

Rates of malignancy associated with juvenile idiopathic arthritis and its treatment

Beukelman¹,

Haynes²,

Curtis³

et al. 2012

Arthritis & Rheumatism

155

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Objective To determine relative rates of incident malignancy among children with juvenile idiopathic arthritis (JIA) with respect to treatment compared to children without JIA Methods Using national U.S. Medicaid data from 2000 through 2005, we identified cohorts of children with JIA and without JIA using physician diagnosis codes and dispensed medication prescriptions. Study follow-up began after a 6 month lag period to exclude prevalent and misdiagnosed malignancies. Treatment with methotrexate and TNF inhibitors was categorized as ever or never exposed. Malignancy outcomes were identified using an adapted version of a previously validated algorithm. Incident malignancies were categorized as possible, probable, or highly probable based on a comprehensive review of all claims. Malignancy rates were standardized to the age, sex, and race distribution of the overall JIA cohort. Standardized incidence ratios (SIR) were calculated using children without JIA (N=321,821) as the referent group. Results The JIA cohort included 7,812 children with a total follow-up time of 12,614 person-years, of whom 1,484 children contributed 2,922 person-years of TNF inhibitor exposure. For all children with JIA versus children without JIA, the SIR was 4.4 (1.8–9.0) for probable and highly probable malignancies. For methotrexate users without TNF inhibitor use, the SIR was 3.9 (0.4–14). Following any use of TNF inhibitors, no probable or highly probable malignancies were identified (SIR 0 (0–9.7)). Conclusions Children with JIA appeared to have an increased rate of incident malignancy compared to children without JIA. JIA treatment, including TNF inhibitors, did not appear significantly associated with the development of malignancy.

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mentioning

confidence: 99%

Rates of malignancy associated with juvenile idiopathic arthritis and its treatment

Beukelman¹,

Haynes²,

Curtis³

et al. 2012

Arthritis & Rheumatism

155

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“…Findings from a recent meta-analysis suggest that etanercept may have the best tolerability profile in RA (30); tuberculosis and other granulomatous infections may occur more frequently with monoclonal anti-TNF antibodies, such as infliximab and adalimumab, than with soluble TNF receptors such as etanercept (42). Long-term safety data are limited even for etanercept, infliximab and adalimumab in RA (43) and interpreting long-term safety data is complicated by the fact that the same adverse events (AEs) are noted to be elevated in patients with autoimmune disease even in those not receiving biological therapy (44). Therefore, anti-TNF agents are contraindicated in patients with multiple sclerosis (41).…”

Section: Differences In Safety Profilementioning

confidence: 99%

Anti-TNF Agents as Therapeutic Choice in Immune-Mediated Inflammatory Diseases: Focus on Adalimumab

Armuzzi¹,

Lionetti

Blandizzi

et al. 2014

Int J Immunopathol Pharmacol

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The complex pathogenesis of immune-mediated inflammatory diseases (IMIDs) has been extensively investigated and dysregulation of cytokines, such as tumour necrosis factor (TNF) has been shown to play a dominant role in the pathogenesis of various IMIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. The subsequent development of biological agents capable of blocking TNF has led to important advances in the pharmacotherapy of such diseases and confirmed the concept of a common pathophysiology among IMIDs with TNF having a predominant role. Five TNF inhibitors have currently been approved for treatment of one or more IMIDs; these include infliximab, etanercept, adalimumab, golimumab and certolizumab pegol. Given the similarities in the pathogenic background of IMIDs, one could expect that anti-TNF agents be similarly effective and with comparable tolerability profiles; however, this may not be the case. Structural and pharmacological differences among the anti-TNF drugs are likely to result in differences in efficacy and tolerability among the agents in the different IMIDs, together with differences in potency, therapeutic dose ranges, dosing regimens, administration routes, and propensity for immunogenicity. Among the five TNF inhibitors approved for treatment of IMIDs, adalimumab has the widest range of indications. Data from controlled clinical trials of adalimumab, showing its excellent efficacy and tolerability in a wide range of indications, are supported by real-world long-term data from observational studies, which confirm the value of adalimumab as a suitable choice in the management of IMIDs.

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“…She explains that even in those individuals noted to have cancer-associated genetic variants, there will be many more individuals who do not develop malignancy than there will be individuals who do [Onel and Onel, 2010].…”

Section: Malignancymentioning

confidence: 99%

Juvenile idiopathic arthritis: management and therapeutic options

Ruth¹,

Passo²

2011

Therapeutic Advances in Musculoskeletal

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The goals of treatment for juvenile idiopathic arthritis (JIA) include: suppression of inflammation, achievement of remission, relief of pain, maintenance of function and doing so with minimal toxicity. Important discoveries over the past 10-15 years have led to more targeted treatments for children with JIA. The International League of Associations for Rheumatology (ILAR) classification system for childhood arthritides, better assessment tools for clinical response, improved definitions of remission, new imaging techniques and evidence in gene expression profiling have all contributed to the development of more targeted treatments. Nonsteroidal anti-inflammatory agents still have a role in mild disease and intraarticular steroid injections continue to be used most commonly in patients with oligoarticular JIA. Disease-modifying agents such as methotrexate have demonstrated efficacy and safety; however, in many patients, the disease remains active despite this treatment. These children now receive more targeted treatment including the tumor necrosis factor alpha (TNFa) inhibitors, interleukin-1 blockade, interleukin-6 blockade, selective costimulation modulators and selective B-cell blockade. The biologic targeted therapies have changed the strategy in which we treat our children with JIA; however, there remains much to be learned about the long-term effects and safety of these medicines.

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Anti–tumor necrosis factor therapy and cancer risk in patients with autoimmune disorders

Cited by 19 publications

References 47 publications

Rates of malignancy associated with juvenile idiopathic arthritis and its treatment

Rates of malignancy associated with juvenile idiopathic arthritis and its treatment

Anti-TNF Agents as Therapeutic Choice in Immune-Mediated Inflammatory Diseases: Focus on Adalimumab

Juvenile idiopathic arthritis: management and therapeutic options

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