Anti–tumor necrosis factor α therapy and the risk of lymphoma in rheumatoid arthritis: No clear answer

Symmons, Deborah; Silman, Alan J.

doi:10.1002/art.20312

Cited by 55 publications

(27 citation statements)

References 22 publications

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“…Of concern it is also the use of other therapeutic agents, including immunosuppressants such as CyA, AZA, and CTX [34][35][36][37], that may lead to LPD by altering immune functions. The question of whether or not there is a causal link between TNF-a antagonists, recently introduced in the therapy of RA, and lymphoma risk has been debated [38][39][40]. A patient included in the present series experienced a spontaneous CR of her LPD developed during treatment with MTX combined with infliximab, following MTX alone [22].…”

Section: Discussionmentioning

confidence: 96%

Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature

et al. 2008

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There are a number of intriguing reports of lymphoproliferative disorders (LPDs) diagnosed during immunosuppressive treatment for underlying autoimmune disease, and spontaneously abated shortly after treatment discontinuation. Such LPDs, completely or partially regressing, occur in the clinical setting of "Methotrexate (MTX)-associated LPDs", recognized by the World Health Organization (WHO) among the "Immunodeficiency-associated LPDs". We identified 26 literature patients achieving spontaneous complete remission (CR) of their LPD, and eight others showing partial remission (PR). Most of them were affected by rheumatoid arthritis, received low-dose and long-term pulsed MTX alone or combined with other immunosuppressants, and developed a lymphoma. By reviewing the patients achieving CR, the following can be drawn: the absence of a unique type of LPD, the occurrence of an increased incidence of diffuse large B cell lymphoma as well as of frequent extranodal involvement, and EBV-infection. Further, CR mostly occurred within 4 weeks after discontinuation of immunosuppressant, and appeared to be persistent overtime. Conversely in the patients experiencing PR, the interval between discontinuation of immunosuppressive treatment and clinical response was mostly reported as longer than 4 weeks; moreover, in many cases the persistence of LPD or its progression induced to start cytotoxic therapy. Increased awareness is needed on the possible occurrence of LPD spontaneous remission following immunosuppressant discontinuation, after that it is therefore advisable to have a careful monitoring of the patient for some weeks, before starting cytotoxic therapy.

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Section: Discussionmentioning

confidence: 96%

Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature

et al. 2008

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“…30 Long-term data to investigate the relative risk of lymphoma in etanercept-treated patients with psoriasis are still accumulating; however, etanercept has been used in the treatment of RA for over 8 years. The risk of lymphoma has been estimated to be elevated 2-to 3-fold in patients with RA, compared with the general population, 31 and the risk of lymphoma increases up to 25.8-fold in RA patients with high levels of inflammation. 32 In a prospective study of 18,572 RA patients, the standardized incidence ratios for lymphomas in patients treated with etanercept was 3.8 (95% confidence interval, 1.9-7.5).…”

Section: Discussionmentioning

confidence: 99%

Etanercept monotherapy in patients with psoriasis: A summary of safety, based on an integrated multistudy database

Gottlieb¹,

Leonardi²,

Goffe

et al. 2006

Journal of the American Academy of Dermatology

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“…Anderson et al reported that several autoimmune conditions are associated with increased risks of myeloid and lymphoid neoplasms, and RA has been associated with an increased risk of acute myeloid leukemia (AML), myelodysplastic syndrome, non-Hodgkin lymphoma, and Hodgkin lymphoma [5,6]. Some factors, such as methotrexate and anti-tumor necrosis factor α treatment [7][8][9][10][11][12][13], disease activities (14), and Epstein-Barr virus [14][15][16][17][18], have also been reported to increase the risk of developing lymphoma in RA patients.…”

Section: Introductionmentioning

confidence: 99%

The age–risk relationship of hematologic malignancies in patients with rheumatoid arthritis: a nationwide retrospective cohort study

et al. 2015

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The risk of hematologic malignancies in rheumatoid arthritis (RA) patients has been an important clinical concern. The information of age effect on the interval from the diagnosis of RA to that of hematologic malignancies is limited. This study aimed to define the age-risk relationship between hematologic malignancies and RA. A retrospective cohort study was conducted nationwide with 17,472 patients and 87,360 controls from the Taiwan National Health Insurance Database covering 1997-2008. The subsequent development of hematologic malignancy was observed. The age-adjusted standardized incidence ratios (SIRs), incidence per 1000 person-years, follow-up duration for the diagnosis of hematologic malignancies, and cumulative hazard rates of hematologic malignancies between RA and controls were analyzed. Significantly higher incidences of both lymphoid and myeloid malignancies were found in male RA patients compared with RA-free patients (SIR 3.36, 95% CI = 2.03-5.57, and SIR: 3.69, 95% CI = 2.46-5.53). A significantly increased overall incidence risk was found in lymphoid malignancies (SIR 3.00, 95% CI = 2.22-4.05) but not significantly increased in myeloid malignancies (SIR 1.54, 95% CI = 0.95-2.50) in female RA. The follow-up duration for hematologic malignancies was significantly shorter in RA patients than in RA-free patients in both males and females (70.70 vs. 103.80 months and 67.73 vs. 100.93 months, respectively). Additionally, higher cumulative hazard rates in both lymphoid and myeloid malignancies were found in male RA patients (p < 0.0001). RA patients have a shorter incubation time to hematological malignancies while comparing to the RA-free people, and the risks are variable in gender and different age groups.

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Anti–tumor necrosis factor α therapy and the risk of lymphoma in rheumatoid arthritis: No clear answer

Cited by 55 publications

References 22 publications

Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature

Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature

Etanercept monotherapy in patients with psoriasis: A summary of safety, based on an integrated multistudy database

The age–risk relationship of hematologic malignancies in patients with rheumatoid arthritis: a nationwide retrospective cohort study

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