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Utilization of biologic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis and cancer

Clinical Rheumatology volume 39, pages 787–794 (2020)Cite this article

Abstract

Introduction

Biologic disease–modifying anti-rheumatic drugs (bDMARDs) interfere with the immune system and could theoretically increase risk of malignancies. However, recent evidence has not substantiated such concerns and physicians are less reluctant in treating patients with underlying cancer with such bDMARDs. We aimed to understand the current utilization patterns of bDMARDs for the treatment of rheumatoid arthritis (RA) in cancer patients.

Methods

We performed a retrospective cohort study of patients with prevalent RA and cancer initially seen at MD Anderson Cancer Center between 2002 and 2014. A cohort of cancer patients was identified from the tumor registry, and patients with RA were identified through ICD-9 codes, followed by review of electronic medical records. We included patients 18 years and older, with a cancer diagnosis, and a diagnosis of RA by a rheumatologist. Patients were followed until 2016.

Results

We identified 431 patients with RA and cancer that met our inclusion criteria. Overall, 111 (26%) received bDMARDs after their cancer diagnosis; of these, 60 (54%) had received bDMARDs prior to their cancer diagnosis and continued to receive this therapy following their diagnosis. Thirteen (22%) switched to a different bDMARD, and the rest continued to receive the same agent after their cancer diagnosis. Of all patients on a bDMARD, 91 (82%) received tumor necrosis factor inhibitors (TNFi).

Conclusions

The treatment landscape of patients with a history of cancer and RA is changing. Future studies evaluating the safety of bDMARDs in patients with a recent history of cancer or with active cancer are needed.

Prior abstract publication

Part of the data of this project was presented as a poster at the 2016 American College of Rheumatology annual meeting.

Zamora NV, Siddhanamatha H, Barbo A, Tayar J, Lin H, Suarez-Almazor M. Utilization of Biologic Therapy in Patients with Rheumatoid Arthritis and Cancer [abstract].Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/utilization-of-biologic-therapy-in-patients-with-rheumatoid-arthritis-and-cancer/. Accessed September 30, 2019.

Key Points
• One in four patients with RA and concomitant cancer received bDMARDs, including TNFi, after their cancer diagnosis, at our institution.
• Half of the patients with RA and cancer who received bDMARDs had initiated therapy prior to the cancer diagnosis, continuing thereafter.

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References

  1. Furst DE, Keystone EC, So AK, Braun J, Breedveld FC, Burmester GR, De Benedetti F, Dorner T, Emery P, Fleischmann R, Gibofsky A, Kalden JR, Kavanaugh A, Kirkham B, Mease P, Rubbert-Roth A, Sieper J, Singer NG, Smolen JS, Van Riel PL, Weisman MH, Winthrop KL (2013) Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012. Ann Rheum Dis 72 Suppl 2:ii2-34. doi:https://doi.org/10.1136/annrheumdis-2013-203348

  2. Amjevita [package insert]. Thousand Oaks, CA: Amgen; 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761024s004lbl.pdf. Accessed 30 Sept 2019

  3. Inflectra [package insert]. Republic of Korea: Celltrion, Inc; 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761024s004lbl.pdf. Accessed 30 Sept 2019

  4. Her M, Kavanaugh A (2016) Alterations in immune function with biologic therapies for autoimmune disease. J Allergy Clin Immunol 137(1):19–27. https://doi.org/10.1016/j.jaci.2015.10.023

    CAS  Article  PubMed  Google Scholar 

  5. Wallis D (2014) Infection risk and biologics: current update. Curr Opin Rheumatol 26(4):404–409. https://doi.org/10.1097/BOR.0000000000000072

    CAS  Article  PubMed  Google Scholar 

  6. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295(19):2275–2285. https://doi.org/10.1001/jama.295.19.2275

    CAS  Article  PubMed  Google Scholar 

  7. Askling J, Fahrbach K, Nordstrom B, Ross S, Schmid CH, Symmons D (2011) Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf 20(2):119–130. https://doi.org/10.1002/pds.2046

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Leombruno JP, Einarson TR, Keystone EC (2009) The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exposure-adjusted pooled analyses of serious adverse events. Ann Rheum Dis 68(7):1136–1145. https://doi.org/10.1136/ard.2008.091025

    CAS  Article  Google Scholar 

  9. Thompson AE, Rieder SW, Pope JE (2011) Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients with early rheumatoid arthritis: a meta-analysis of randomized controlled trials. Arthritis Rheum 63(6):1479–1485. https://doi.org/10.1002/art.30310

    CAS  Article  PubMed  Google Scholar 

  10. Lan JL, Tseng CH, Chen JH, Cheng CF, Liang WM, Tsay GJ (2017) Reduced risk of all-cancer and solid cancer in Taiwanese patients with rheumatoid arthritis treated with etanercept, a TNF-alpha inhibitor. Medicine (Baltimore) 96(7):e6055. https://doi.org/10.1097/MD.0000000000006055

    CAS  Article  Google Scholar 

  11. Wu CY, Chen DY, Shen JL, Ho HJ, Chen CC, Kuo KN, Liu HN, Chang YT, Chen YJ (2014) The risk of cancer in patients with rheumatoid arthritis taking tumor necrosis factor antagonists: a nationwide cohort study. Arthritis Res Ther 16(5):449. https://doi.org/10.1186/s13075-014-0449-5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Lopez-Olivo MA, Colmegna I, Karpes AR, Qi SR, Zamora NV, Sharma R, Pratt G, Suarez-Almazor ME (2019) Systematic review of recommendations on the use of disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and cancer. Arthritis Care Res. https://doi.org/10.1002/acr.23865

  13. Dixon WG, Watson KD, Lunt M, Mercer LK, Hyrich KL, Symmons DP, British Society For Rheumatology Biologics Register Control Centre C, British Society for Rheumatology Biologics R (2010) Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register. Arthritis Care Res 62(6):755–763. https://doi.org/10.1002/acr.20129

    CAS  Article  Google Scholar 

  14. Silva-Fernandez L, Lunt M, Kearsley-Fleet L, Watson KD, Dixon WG, Symmons DP, Hyrich KL, British Society for Rheumatology Biologics Register Control Centre C (2016) The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis. Rheumatology (Oxford) 55(11):2033–2039. https://doi.org/10.1093/rheumatology/kew314

    CAS  Article  Google Scholar 

  15. Strangfeld A, Hierse F, Rau R, Burmester GR, Krummel-Lorenz B, Demary W, Listing J, Zink A (2010) Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT. Arthritis Res Ther 12(1):R5. https://doi.org/10.1186/ar2904

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Raaschou P, Frisell T, Askling J, Group AS (2015) TNF inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis: a nationwide cohort study. Ann Rheum Dis 74(12):2137–2143. https://doi.org/10.1136/annrheumdis-2014-205745

    CAS  Article  PubMed  Google Scholar 

  17. Raaschou P, Soderling J, Turesson C, Askling J, Group AS (2018) Tumor necrosis factor inhibitors and cancer recurrence in Swedish patients with rheumatoid arthritis: a nationwide population-based cohort study. Ann Intern Med 169(5):291–299. https://doi.org/10.7326/M17-2812

    Article  PubMed  Google Scholar 

  18. Xie W, Xiao S, Huang Y, Sun X, Gao D, Ji L, Li G, Zhang Z (2019) A meta-analysis of biologic therapies on risk of new or recurrent cancer in patients with rheumatoid arthritis and a prior malignancy. Rheumatology (Oxford). https://doi.org/10.1093/rheumatology/kez475

  19. Schemper M, Smith TL (1996) A note on quantifying follow-up in studies of failure time. Control Clin Trials 17(4):343–346

    CAS  Article  Google Scholar 

  20. Søgaard M, Thomsen RW, Bossen KS, Sørensen HT, Nørgaard M (2013) The impact of comorbidity on cancer survival: a review. Clin Epidemiol 5(Suppl 1):3–29

    Article  Google Scholar 

  21. Ahern TP, Lash TL, Thwin SS, Silliman RA (2009) Impact of acquired comorbidities on all-cause mortality rates among older breast cancer survivors. Med Care 47(1):73–79

    Article  Google Scholar 

  22. Borggreven PA, Kuik DJ, Langendijk JA, Doornaert P, de Bree R, Leemans CR (2005) Severe comorbidity negatively influences prognosis in patients with oral and oropharyngeal cancer after surgical treatment with microvascular reconstruction. Oral Oncol 41(4):358–364

    Article  Google Scholar 

  23. Braithwaite D, Moore DH, Satariano WA, Kwan ML, Hiatt RA, Kroenke C, Caan BJ (2012) Prognostic impact of comorbidity among long-term breast cancer survivors: results from the LACE study. Cancer Epidem Biomar 21(7):1115–1125. https://doi.org/10.1158/1055-9965.Epi-11-1228

    Article  Google Scholar 

  24. Chamie K, Daskivich TJ, Kwan L, Labo J, Dash A, Greenfield S, Litwin MS (2012) Comorbidities, treatment and ensuing survival in men with prostate cancer. J Gen Intern Med 27(5):492–499

    Article  Google Scholar 

  25. Colinet B, Jacot W, Bertrand D, Lacombe S, Bozonnat M, Daures J, Pujol J (2005) A new simplified comorbidity score as a prognostic factor in non-small-cell lung cancer patients: description and comparison with the Charlson’s index. Br J Cancer 93(10):1098–1105

    CAS  Article  Google Scholar 

  26. De Marco M, Janssen-Heijnen M, Van der Heijden L, Coebergh J (2000) Comorbidity and colorectal cancer according to subsite and stage: a population-based study. Eur J Cancer 36(1):95–99

    Article  Google Scholar 

  27. Satariano WA, Ragland DR (1994) The effect of comorbidity on 3-year survival of women with primary breast cancer. Ann Intern Med 120(2):104–110

    CAS  Article  Google Scholar 

  28. Yancik R, Wesley MN, Ries LA, Havlik RJ, Long S, Edwards BK, Yates JW (1998) Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients. Cancer 82(11):2123–2134

    CAS  Article  Google Scholar 

  29. Lopez-Olivo MA, Tayar JH, Martinez-Lopez JA, Pollono EN, Cueto JP, Gonzales-Crespo MR, Fulton S, Suarez-Almazor ME (2012) Risk of malignancies in patients with rheumatoid arthritis treated with biologic therapy: a meta-analysis. JAMA 308(9):898–908. https://doi.org/10.1001/2012.jama.10857

    CAS  Article  PubMed  Google Scholar 

  30. Ramiro S, Sepriano A, Chatzidionysiou K, Nam JL, Smolen JS, van der Heijde D, Dougados M, van Vollenhoven R, Bijlsma JW, Burmester GR (2017) Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 76(6):1101–1136

    Article  Google Scholar 

  31. Mercer LK, Askling J, Raaschou P, Dixon WG, Dreyer L, Hetland ML, Strangfeld A, Zink A, Mariette X, Finckh A, Canhao H, Lannone F, Zavada J, Morel J, Gottenberg JE, Hyrich KL, Listing J (2017) Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers. Ann Rheum Dis 76(2):386–391. https://doi.org/10.1136/annrheumdis-2016-209285

    Article  PubMed  Google Scholar 

  32. Aaltonen KJ, Joensuu JT, Virkki L, Sokka T, Aronen P, Relas H, Valleala H, Rantalaiho V, Pirilä L, Puolakka K (2015) Rates of serious infections and malignancies among patients with rheumatoid arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy. J Rheumatol 42(3):372–378

    CAS  Article  Google Scholar 

  33. Hellgren K, Baecklund E, Backlin C, Sundstrom C, Smedby K, Askling J (2017) Rheumatoid arthritis and risk of malignant lymphoma: is the risk still increased? Arthritis Rheum 69(4):700–708

    CAS  Article  Google Scholar 

  34. Setoguchi S, Solomon DH, Weinblatt ME, Katz JN, Avorn J, Glynn RJ, Cook EF, Carney G, Schneeweiss S (2006) Tumor necrosis factor α antagonist use and cancer in patients with rheumatoid arthritis. Arthritis Rheum 54(9):2757–2764

    CAS  Article  Google Scholar 

  35. Singh JA, Saag KG, Bridges SL, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH (2016) 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheum 68(1):1–26

    Google Scholar 

  36. Strangfeld A, Pattloch D, Herzer P, Edelmann E, Zinke S, Aringer M, Listing J, Zink A (2013) Risk of cancer recurrence or new tumors in RA patients with prior malignancies treated with various biologic agents. Arthritis Rheum-Us 65:S342–S342

    Article  Google Scholar 

  37. Raaschou P, Simard JF, Neovius M, Askling J, Group ARTiSS (2011) Does cancer that occurs during or after anti–tumor necrosis factor therapy have a worse prognosis? A national assessment of overall and site-specific cancer survival in rheumatoid arthritis patients treated with biologic agents. Arthritis Rheum 63(7):1812–1822

    CAS  Article  Google Scholar 

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Funding

This research was supported by the Advancing Science through Pfizer–Investigator Research Exchange program, a competitive grants program supported by Pfizer, to Maria E. Suarez-Almazor. Pfizer ASPIRE Rheumatology award #WI195021. The statistical analysis was supported in part by the Cancer Center Support Grant (NCI Grant P30 CA016672).

Author information

Affiliations

  1. Department of General Internal Medicine, Section of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Xerxes Pundole, Jean Tayar & Maria E. Suarez-Almazor

  2. Sección Reumatología, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina

    Natalia V. Zamora

  3. Department of Data Integrity and Analytics, Augusta University Medical Center, Augusta, Georgia

    Harish Siddhanamatha

  4. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Heather Lin, Leung Cheuk Hong & Liang Li

Authors
  1. Xerxes Pundole
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  2. Natalia V. Zamora
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  3. Harish Siddhanamatha
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  4. Heather Lin
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  5. Jean Tayar
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  6. Leung Cheuk Hong
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  7. Liang Li
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  8. Maria E. Suarez-Almazor
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Corresponding author

Correspondence to Maria E. Suarez-Almazor.

Ethics declarations

Institutional review board approval was obtained before any data were collected for this study. The use of patient information complied with the Health Insurance Portability and Accountability Act, and sensitive patient data were protected in the data analysis.

Conflict of interest

Xerxes Pundole—none

Natalia V. Zamora—none

Harish Siddhanamatha—none

Heather Lin—none

Jean Tayar—none

Leung Cheuk Hong—none

Liang Li—none

Maria E. Suarez-Almazor – Dr. Suarez-Almazor has been a consultant for Pfizer, AbbVie and Agile Pharmaceuticals

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Pundole, X., Zamora, N.V., Siddhanamatha, H. et al. Utilization of biologic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis and cancer. Clin Rheumatol 39, 787–794 (2020). https://doi.org/10.1007/s10067-019-04874-x

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  • DOI: https://doi.org/10.1007/s10067-019-04874-x

Keywords

  • Biologic
  • Cancer
  • DMARD
  • Rheumatoid arthritis
  • Tumor necrosis factor