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13-05-2015 | Comorbidities | Article

Incidence of malignancy in adult patients with rheumatoid arthritis: a meta-analysis

Journal: Arthritis Research & Therapy

Authors: Teresa A. Simon, Adam Thompson, Kunal K. Gandhi, Marc C. Hochberg, Samy Suissa

Publisher: BioMed Central

Abstract

Introduction

Patients with rheumatoid arthritis (RA) are at an increased risk of malignancies compared with the general population. This has raised concerns regarding these patients, particularly with the widespread use of immunomodulating therapies, including biologic disease-modifying antirheumatic drugs (DMARDs). We performed a systematic literature review and analysis to quantify the incidence of malignancies in patients with RA and the general population to update previously published data.

Methods

A literature search was conducted that was consistent with and similar to that in a meta-analysis published in 2008. MEDLINE, BIOSIS Previews, Embase, Derwent Drug File and SciSearch databases were searched using specified search terms. Predefined inclusion criteria identified the relevant observational studies published between 2008 and 2014 that provided estimates of relative risk of malignancy in patients with RA compared with the general population. Risk data on overall malignancy and site-specific malignancies (lymphoma, melanoma and lung, colorectal, breast, cervical and prostate cancer) were extracted. The standardized incidence ratios (SIRs; a measure of risk) relative to the general population were evaluated and compared with published rates.

Results

A total of nine publications met the inclusion criteria. Seven of these reported SIRs for overall malignancy; eight for lymphoma, melanoma, and lung, colorectal and breast cancer; seven for prostate cancer; and four for cervical cancer. Compared with those in the general population, the SIR estimates for patients with RA suggest a modest increased risk in overall malignancy, as previously observed. Patients with RA continued to show an increased risk of lymphoma and lung cancer compared with the general population. Overall, SIR estimates for colorectal and breast cancers continued to show a decrease in risk, whereas cervical cancer, prostate cancer and melanoma appeared to show no consistent trend in risk among patients with RA compared with the general population.

Conclusions

The additional data evaluated here are consistent with previously reported data. Patients with RA are at an increased risk of lung and lymphoma malignancies compared with the general population. Quantifying differences in malignancy rates between non-biologic and biologic DMARD-treated patients with RA may further highlight which malignancies may be related to treatment rather than to the underlying disease.

Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 3rd CO, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569–81.CrossRefPubMed

Smolen JS, Landewé R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69:964–75.CrossRefPubMedPubMedCentral

Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64:625–39.CrossRef

Love T, Solomon DH. The relationship between cancer and rheumatoid arthritis: still a large research agenda. Arthritis Res Ther. 2008;10:109.CrossRefPubMedPubMedCentral

Cush JJ, Dao KH. Malignancy risks with biologic therapies. Rheum Dis Clin North Am. 2012;38:761–70.CrossRefPubMed

Smitten AL, Simon TA, Hochberg MC, Suissa S. A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther. 2008;10:R45.CrossRefPubMedPubMedCentral

Kim SC, Glynn RJ, Giovannucci E, Hernández-Díaz S, Liu J, Feldman S, et al. Risk of high-grade cervical dysplasia and cervical cancer in women with systemic inflammatory diseases: a population-based cohort study. Ann Rheum Dis. 2015;74:1360–7.CrossRefPubMed

Chakravarty EF, Farmer ER. Risk of skin cancer in the drug treatment of rheumatoid arthritis. Expert Opin Drug Saf. 2008;7:539–46.CrossRefPubMed

Szekanecz Z, Szekanecz É, Bakó G, Shoenfeld Y. Malignancies in autoimmune rheumatic disease – a mini-review. Gerontology. 2011;57:3–10.CrossRefPubMed

10.

Hellgren K, Smedby KE, Feltelius N, Baecklund E, Askling J. Do rheumatoid arthritis and lymphoma share risk factors? A comparison of lymphoma and cancer risks before and after diagnosis of rheumatoid arthritis. Arthritis Rheum. 2010;62:1252–8.CrossRefPubMed

11.

DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMed

12.

Chen YJ, Chang YT, Wang CB, Wu CY. The risk of cancer in patients with rheumatoid arthritis: a nationwide cohort study in Taiwan. Arthritis Rheum. 2011;63:352–8.CrossRefPubMed

13.

Dreyer L, Mellemkjær L, Andersen AR, Bennett P, Poulsen UE, Juulsgaard Elligsen T, et al. Incidences of overall and site specific cancers in TNFα inhibitor treated patients with rheumatoid arthritis and other arthritides – a follow-up study from the DANBIO Registry. Ann Rheum Dis. 2013;72:79–82.CrossRefPubMed

14.

Hemminki K, Li X, Sundquist K, Sundquist J. Cancer risk in hospitalized rheumatoid arthritis patients. Rheumatology. 2008;47:698–701.CrossRefPubMed

15.

Mercer L, Davies R, Galloway JB, Low A, Lunt M, Dixon WG, et al. Risk of cancer in patients receiving non-biologic disease-modifying therapy for rheumatoid arthritis compared with the UK general population. Rheumatology (Oxford). 2013;52:91–8.CrossRef

16.

Parikh-Patel A, White RH, Allen M, Cress R. Risk of cancer among rheumatoid arthritis patients in California. Cancer Causes Control. 2009;20:1001–10.CrossRefPubMedPubMedCentral

17.

Yamada T, Nakajima A, Inoue E, Tanaka E, Taniguchi A, Momohara S, et al. Incidence of malignancy in Japanese patients with rheumatoid arthritis. Rheumatol Int. 2011;31:1487–92.CrossRefPubMed

18.

Kim YJ, Shim JS, Choi CB, Bae SC. Mortality and incidence of malignancy in Korean patients with rheumatoid arthritis. J Rheumatol. 2012;39:226–32.CrossRefPubMed

19.

Buchbinder R, Barber M, Heuzenroeder L, Wluka AE, Giles G, Hall S, et al. Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum. 2008;59:794–9.CrossRefPubMed

20.

Abásolo L, Júdez E, Descalzo MÁ, González-Álvaro I, Jover JA, Carmona L, et al. Cancer in rheumatoid arthritis: occurrence, mortality and associated factors in a South European population. Semin Arthritis Rheum. 2008;37:388–97.CrossRefPubMed

21.

Askling J, Fored CM, Brandt L, Baecklund E, Bertilsson L, Feltelius N, et al. Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists. Ann Rheum Dis. 2005;64:1421–6.CrossRefPubMedPubMedCentral

22.

Cibere J, Sibley J, Haga M. Rheumatoid arthritis and the risk of malignancy. Arthritis Rheum. 1997;40:1580–6.CrossRefPubMed

23.

Franklin J, Lunt M, Bunn D, Symmons D, Silman A. Influence of inflammatory polyarthritis on cancer incidence and survival: results from a community-based prospective study. Arthritis Rheum. 2007;56:790–8.CrossRefPubMed

24.

Gridley G, McLaughlin JK, Ekbom A, Klareskog L, Adami HO, Hacker DG, et al. Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst. 1993;85:307–11.CrossRefPubMed

25.

Mellemkjaer L, Linet MS, Gridley G, Frisch M, Møller H, Olsen JH. Rheumatoid arthritis and cancer risk. Eur J Cancer. 1996;32A:1753–7.CrossRefPubMed

26.

Moritomo H, Ueda T, Hiyama T, Hosono N, Mori S, Komatsubara Y. The risk of cancer in rheumatoid patients in Japan. Scand J Rheumatol. 1995;24:157–9.CrossRefPubMed

27.

Thomas E, Brewster DH, Black RJ, Macfarlane GJ. Risk of malignancy among patients with rheumatic conditions. Int J Cancer. 2000;88:497–502.CrossRefPubMed

28.

Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum. 2007;56:2886–95.CrossRefPubMed

29.

Ekström K, Hjalgrim H, Brandt L, Baecklund E, Klareskog L, Ekbom A, et al. Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-degree relatives. Arthritis Rheum. 2003;48:963–70.CrossRefPubMed

30.

Geborek P, Bladström A, Turesson C, Gulfe A, Petersson IF, Saxne T, et al. Tumour necrosis factor blockers do not increase overall tumour risk in patients with rheumatoid arthritis, but may be associated with an increased risk of lymphomas. Ann Rheum Dis. 2005;64:699–703.CrossRefPubMedPubMedCentral

31.

Kauppi M, Pukkala E, Isomaki H. Low incidence of colorectal cancer in patients with rheumatoid arthritis. Clin Exp Rheumatol. 1996;14:551–3.PubMed

32.

Matteson EL, Hickey AR, Maguire L, Tilson HH, Urowitz MB. Occurrence of neoplasia in patients with rheumatoid arthritis enrolled in a DMARD Registry. Rheumatoid Arthritis Azathioprine Registry Steering Committee. J Rheumatol. 1991;18:809–14.PubMed

33.

Wolfe F, Michaud K. The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation. Arthritis Rheum. 2007;56:1433–9.CrossRefPubMed

34.

Kauppi M, Pukkala E, Isomäki H. Elevated incidence of hematologic malignancies in patients with Sjögren’s syndrome compared with patients with rheumatoid arthritis (Finland). Cancer Causes Control. 1997;8:201–4.CrossRefPubMed

35.

Mariette X, Cazals-Hatem D, Warszawki J, Liote F, Balandraud N, Sibilia J, et al. Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood. 2002;99:3909–15.CrossRefPubMed

36.

Setoguchi S, Solomon DH, Weinblatt ME, Katz JN, Avorn J, Glynn RJ, et al. Tumor necrosis factor α antagonist use and cancer in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54:2757–64.CrossRefPubMed

37.

McKendry RJ, Dale P. Adverse effects of low dose methotrexate therapy in rheumatoid arthritis. J Rheumatol. 1993;20:1850–6.PubMed

38.

Kauppi M, Pukkala E, Isomäki H. Excess risk of lung cancer in patients with rheumatoid arthritis. J Rheumatol. 1996;23:1484–5.PubMed

39.

Mariette X, Matucci-Cerinic M, Pavelka K, Taylor P, van Vollenhoven R, Heatley R, et al. Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis. Ann Rheum Dis. 2011;70:1895–904.CrossRefPubMed

40.

Park HJ, Ranganathan P. TNF-α antagonism and cancer risk in rheumatoid arthritis: is continued vigilance warranted? Discov Med. 2012;13:229–34.PubMed

41.

Le Blay P, Mouterde G, Barnetche T, Morel J, Combe B. Risk of malignancy including non-melanoma skin cancers with anti-tumor necrosis factor therapy in patients with rheumatoid arthritis: a meta-analysis of registries and systematic review. Clin Exp Rheumatol. 2012;30:756–64.PubMed

42.

Askling J, Fahrbach K, Nordstrom B, Ross S, Schmid CH, Symmons D. Cancer risk with tumor necrosis factor α (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf. 2011;20:119–30.CrossRefPubMed

43.

Damjanov N, Nurmohamed MT, Szekanecz Z. Biologics, cardiovascular effects and cancer. BMC Med. 2014;12:48. doi:10.1186/1741-7015-12-48.CrossRefPubMedPubMedCentral

44.

Askling J, Baecklund E, Granath F, Geborek P, Fored M, Backlin C, et al. Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register. Ann Rheum Dis. 2009;68:648–53.CrossRefPubMed

45.

Simon TA, Smitten AL, Franklin J, Askling J, Lacaille D, Wolfe F, et al. Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epidemiological assessment. Ann Rheum Dis. 2009;68:1819–26.CrossRefPubMedPubMedCentral