Skip to main content

Advertisement

SpringerLink
Log in

Overall survival in patients with rheumatoid arthritis and solid malignancies receiving biologic disease-modifying antirheumatic therapy

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Introduction/objectives

The effects of biologic disease–modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and cancer are largely unknown. We examined overall survival (OS) in patients with RA and solid malignancies receiving bDMARDs.

Methods

We performed a retrospective cohort study of patients with RA and solid malignancies seen at MD Anderson Cancer Center between 2002 and 2014. Cox proportional hazard regression models, stratified by tumor type and stage, were fit evaluating use of bDMARDs as a time fixed and time varying covariate.

Results

We identified 431 RA patients with solid malignancies: 111 (26%) received bDMARDs after their cancer diagnosis. Median OS from cancer diagnosis was 16.1 years. Of the patients receiving bDMARDs, most had localized disease, and only 14 (13%) had advanced cancer. In the stratified Cox models no statistically significant differences were observed between patients who received tumor necrosis factor inhibitors (TNFi) or patients who received nonTNFi, compared with those who did not receive bDMARDs (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.31, 1.44; HR, 1.10; 95% CI, 0.26, 4.60 respectively). In breast cancer patients, those receiving TNFi or nonTNFi had a numerically higher but statistically nonsignificant HR compared with those who did not receive bDMARD: HR, 1.40 (95% CI, 0.42, 4.73), and HR, 1.37 (95% CI, 0.22, 8.42) respectively.

Conclusion

No significant differences in OS were observed between patients who received bDMARDs and those who did not. Additional data is needed to evaluate other cancer outcomes such as recurrence and progression, and patients with advanced cancer.

Key Points

•We found no statistically significant differences in OS between patients with RA and concomitant solid malignancies who received bDMARDs and those who did not.

•Most patients who received bDMARDs had been diagnosed with early stage cancer

•As few patients with advanced cancer received bDMARDs safety for this group cannot be established

•No significant differences were observed between TNFi and nonTNFi, but the sample size was small

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Balkwill F (2009) Tumour necrosis factor and cancer. Nat Rev Cancer 9:361–371

    Article  CAS  Google Scholar 

  2. Lebrec H, Ponce R, Preston BD, Iles J, Born TL, Hooper M (2015) Tumor necrosis factor, tumor necrosis factor inhibition, and cancer risk. Curr Med Res Opin 31:557–574

    Article  CAS  Google Scholar 

  3. Tarella C, Passera R, Magni M, Benedetti F, Rossi A, Gueli A, Patti C, Parvis G, Ciceri F, Gallamini A, Cortelazzo S, Zoli V, Corradini P, Carobbio A, Mulé A, Bosa M, Barbui A, di Nicola M, Sorio M, Caracciolo D, Gianni AM, Rambaldi A (2011) Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab: a 20-year retrospective follow-up study in patients with lymphoma. J Clin Oncol 29:814–824

    Article  CAS  Google Scholar 

  4. Askling J, Bongartz T (2008) Malignancy and biologic therapy in rheumatoid arthritis. Curr Opin Rheumatol 20:334–339

    Article  CAS  Google Scholar 

  5. 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 295:2275–2285

    Article  CAS  Google Scholar 

  6. Callegari PE, Schaible TF, Boscia JA (2006) Risk of serious infections and malignancies with anti-TNF antibody therapy in rheumatoid arthritis. Jama 296:2201–2204

    Article  Google Scholar 

  7. Geborek P, Bladström A, Turesson C, Gulfe A, Petersson IF, Saxne T, Olsson H, Jacobsson LT (2005) 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 64:699–703

    Article  CAS  Google Scholar 

  8. 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 54:2757–2764

    Article  CAS  Google Scholar 

  9. 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:R5

    Article  CAS  Google Scholar 

  10. 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 169:291–299

    Article  Google Scholar 

  11. Dreyer L, Cordtz RL, Hansen IMJ, Kristensen LE, Hetland ML, Mellemkjaer L (2018) Risk of second malignant neoplasm and mortality in patients with rheumatoid arthritis treated with biological DMARDs: a Danish population-based cohort study. Ann Rheum Dis 77:510–514

    Article  Google Scholar 

  12. Waljee AK, Higgins PDR, Jensen CB, Villumsen M, Cohen-Mekelburg SA, Wallace BI, Berinstein JA, Allin KH, Jess T (2020) Anti-tumour necrosis factor-alpha therapy and recurrent or new primary cancers in patients with inflammatory bowel disease, rheumatoid arthritis, or psoriasis and previous cancer in Denmark: a nationwide, population-based cohort study. Lancet Gastroenterol Hepatol 5(3):276–284

    Article  Google Scholar 

  13. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, O’Dell J, Winthrop KL, Beukelman T, Bridges SL Jr, Chatham WW, Paulus HE, Suarez-almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG (2012) 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 64:625–639

    Article  CAS  Google Scholar 

  14. Bombardier C, Hazlewood GS, Akhavan P et al (2012) Canadian rheumatology association recommendations for the pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs: part II safety. J Rheumatol 39:1583–1602

    Article  CAS  Google Scholar 

  15. Singh JA, Saag KG, Bridges SL Jr et al (2016) 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheum 68:1–26

    Google Scholar 

  16. Lopez-Olivo MA, Colmegna I, Karpes AR et al (2020) Systematic review of recommendations on the use of disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and cancer. Arthritis Care Res 72(3):309–318

    Article  Google Scholar 

  17. Pappas DA, Rebello S, Liu M, Schenfeld J, Li YF, Collier DH, Accortt NA (2019) Therapy with biologic agents after diagnosis of solid malignancies: results from the Corrona Registry. J Rheumatol 46:1438–1444

    Article  CAS  Google Scholar 

  18. Pundole X, Zamora NV, Siddhanamatha H, Lin H, Tayar J, Hong LC, Li L, Suarez-Almazor ME (2020) Utilization of biologic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis and cancer. Clin Rheumatol 39(3):787–794

    Article  Google Scholar 

  19. Mariette X, Matucci-Cerinic M, Pavelka K, Taylor P, van Vollenhoven R, Heatley R, Walsh C, Lawson R, Reynolds A, Emery P (2011) Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis. Ann Rheum Dis 70:1895–1904

    Article  Google Scholar 

  20. Bongartz T, Warren FC, Mines D, Matteson EL, Abrams KR, Sutton AJ (2009) Etanercept therapy in rheumatoid arthritis and the risk of malignancies: a systematic review and individual patient data meta-analysis of randomised controlled trials. Ann Rheum Dis 68:1177–1183

    Article  CAS  Google Scholar 

  21. Xie W, Xiao S, Huang Y, Sun X, Gao D, Ji LL, Li G, Zhang Z (2020) A meta-analysis of biologic therapies on risk of new or recurrent cancer in patients with rheumatoid arthritis and a prior malignancy. Rheumatology (Oxford) 59(5):930–939

    Article  Google Scholar 

  22. Howlader N, Noone A, Krapcho M, et al. (2019) SEER Cancer Statistics Review, 1975–2016, National Cancer Institute Bethesda, MD. National Cancer Institute 1423–37

Download references

Funding

This research was supported by the Advancing Science through Pfizer–Investigator Research Exchange program, a competitive grants program supported by Pfizer, Pfizer ASPIRE Rheumatology award #WI195021.

The statistical analysis was supported in part by the Cancer Center Support Grant (NCI Grant P30 CA016672).

Author information

Authors and Affiliations

  1. Department of Health Services Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Xerxes Pundole & 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, GA, USA

    Harish Siddhanamatha

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

    Heather Lin, Cheuk Hong Leung & Liang Li

  5. Department of General Internal Medicine, Section of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jean Tayar & Maria E. Suarez-Almazor

Authors
  1. Xerxes Pundole
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natalia V. Zamora
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harish Siddhanamatha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Heather Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean Tayar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cheuk Hong Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maria E. Suarez-Almazor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria E. Suarez-Almazor.

Ethics declarations

Conflict of interest

Xerxes Pundole—none

Natalia V. Zamora—none

Harish Siddhanamatha—none

Heather Lin—none

Cheuk Hong Leung—none

Natalia V. Zamora—none.

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

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Prior abstract publication

Part of the data of this project was presented as a poster at the 2018 American College of Rheumatology annual meeting.

Pundole X, Zamora N, Siddhanamatha H, Tayar J, Leung CH, Lin H, Suarez-Almazor M. Time Dependent Effect of Biologic Therapy on Overall Survival in Patients with Rheumatoid Arthritis and Cancer [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/time-dependent-effect-of-biologic-therapy-on-overall-survival-in-patients-with-rheumatoid-arthritis-and-cancer/. Accessed November 11, 2019

Electronic supplementary material

ESM 1

(DOCX 42 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pundole, X., Zamora, N.V., Siddhanamatha, H. et al. Overall survival in patients with rheumatoid arthritis and solid malignancies receiving biologic disease-modifying antirheumatic therapy. Clin Rheumatol 39, 2943–2950 (2020). https://doi.org/10.1007/s10067-020-05318-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-020-05318-7

Keywords

Search

Navigation