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Published in: Rheumatology and Therapy 2/2017

Open Access 01-12-2017 | Brief Report

Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA Registry

Authors: Vibeke Strand, Paul Miller, Setareh A. Williams, Katherine Saunders, Shannon Grant, Joel Kremer

Published in: Rheumatology and Therapy | Issue 2/2017

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Abstract

Introduction

Despite the availability of multiple effective therapies, discontinuation/switching of treatment is common for many patients with rheumatoid arthritis (RA). This study was designed to examine initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) within the Consortium of Rheumatology Researchers of North America (Corrona) RA Registry, and characterize reasons for discontinuation.

Methods

Inclusion criteria were: Corrona-registered adults (≥18 years) with RA (2002–2011); age of RA onset: ≥16 years; ≥6 months’ follow-up after initiation of first/subsequent bDMARD. Patients receiving both tumor necrosis factor antagonists and non-TNF antagonists were included. Treatment discontinuation was defined as first report of stopping initial therapy or initiation of new bDMARD at/between visits, using a follow-up physician questionnaire.

Results

Overall, 6209 patients met inclusion criteria and 80.7% received TNF antagonists. Median time to discontinuation/change of therapy was 25.1 months (26.5 months with TNF antagonists vs. 20.5 months with non-TNF antagonists; log-rank p < 0.0001); 82.2, 67.3, and 51.1% of patients remained on therapy at 6, 12, and 24 months, respectively. Reasons for discontinuation were captured for 49.2% of patients, including: loss of efficacy (35.8%); physician preference (27.8%); safety (20.1%); patient preference (17.9%); and no access to treatment (9.0%). Baseline factors with greatest correlation to discontinuation were modified Health Assessment Questionnaire scores, patient-reported anxiety/depression, initiation of bDMARD treatment in 2007–2010 versus 2002–2003, and Clinical Disease Activity Index scores.

Conclusions

Almost one-third of patients in the US discontinue currently available bDMARD therapies for RA by 12 months and almost half by 24 months, most commonly due to loss of efficacy.

Funding

Corrona LLC and MedImmune.
Literature
2.
go back to reference Nam JL, Winthrop KL, van Vollenhoven RF, Pavelka K, Valesini G, Hensor EM, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis. 2010;69(6):976–86. doi:10.1136/ard.2009.126573.CrossRefPubMed Nam JL, Winthrop KL, van Vollenhoven RF, Pavelka K, Valesini G, Hensor EM, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis. 2010;69(6):976–86. doi:10.​1136/​ard.​2009.​126573.CrossRefPubMed
3.
go back to reference Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R, Lopez-Olivo MA, et al. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Sao Paulo Med J. 2010;128(5):309–10.CrossRefPubMed Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R, Lopez-Olivo MA, et al. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Sao Paulo Med J. 2010;128(5):309–10.CrossRefPubMed
4.
go back to reference Smolen JS. Treat-to-target: rationale and strategies. Clin Exp Rheumatol. 2012;30(4 Suppl 73):S2–6.PubMed Smolen JS. Treat-to-target: rationale and strategies. Clin Exp Rheumatol. 2012;30(4 Suppl 73):S2–6.PubMed
5.
6.
go back to reference Russell AS. Quality-of-life assessment in rheumatoid arthritis. Pharmacoeconomics. 2008;26(10):831–46.CrossRefPubMed Russell AS. Quality-of-life assessment in rheumatoid arthritis. Pharmacoeconomics. 2008;26(10):831–46.CrossRefPubMed
9.
go back to reference Alivernini S, Laria A, Gremese E, Zoli A, Ferraccioli G. ACR70-disease activity score remission achievement from switches between all the available biological agents in rheumatoid arthritis: a systematic review of the literature. Arthritis Res Ther. 2009;11(6):R163. doi:10.1186/ar2848.CrossRefPubMedPubMedCentral Alivernini S, Laria A, Gremese E, Zoli A, Ferraccioli G. ACR70-disease activity score remission achievement from switches between all the available biological agents in rheumatoid arthritis: a systematic review of the literature. Arthritis Res Ther. 2009;11(6):R163. doi:10.​1186/​ar2848.CrossRefPubMedPubMedCentral
10.
go back to reference Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ. Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum. 2007;56(1):13–20. doi:10.1002/art.22331.CrossRefPubMed Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ. Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum. 2007;56(1):13–20. doi:10.​1002/​art.​22331.CrossRefPubMed
11.
go back to reference Jamnitski A, Bartelds GM, Nurmohamed MT, van Schouwenburg PA, van Schaardenburg D, Stapel SO, et al. The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept. Ann Rheum Dis. 2011;70(2):284–8. doi:10.1136/ard.2010.135111.CrossRefPubMed Jamnitski A, Bartelds GM, Nurmohamed MT, van Schouwenburg PA, van Schaardenburg D, Stapel SO, et al. The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept. Ann Rheum Dis. 2011;70(2):284–8. doi:10.​1136/​ard.​2010.​135111.CrossRefPubMed
12.
go back to reference Lloyd S, Bujkiewicz S, Wailoo AJ, Sutton AJ, Scott D. The effectiveness of anti-TNF-alpha therapies when used sequentially in rheumatoid arthritis patients: a systematic review and meta-analysis. Rheumatology (Oxford). 2010;49(12):2313–21. doi:10.1093/rheumatology/keq169.CrossRef Lloyd S, Bujkiewicz S, Wailoo AJ, Sutton AJ, Scott D. The effectiveness of anti-TNF-alpha therapies when used sequentially in rheumatoid arthritis patients: a systematic review and meta-analysis. Rheumatology (Oxford). 2010;49(12):2313–21. doi:10.​1093/​rheumatology/​keq169.CrossRef
13.
go back to reference Soliman MM, Hyrich KL, Lunt M, Watson KD, Symmons DP, Ashcroft DM. Rituximab or a second anti-tumor necrosis factor therapy for rheumatoid arthritis patients who have failed their first anti-tumor necrosis factor therapy? Comparative analysis from the British Society for Rheumatology Biologics Register. Arthritis Care Res. 2012;64(8):1108–15. doi:10.1002/acr.21663.CrossRef Soliman MM, Hyrich KL, Lunt M, Watson KD, Symmons DP, Ashcroft DM. Rituximab or a second anti-tumor necrosis factor therapy for rheumatoid arthritis patients who have failed their first anti-tumor necrosis factor therapy? Comparative analysis from the British Society for Rheumatology Biologics Register. Arthritis Care Res. 2012;64(8):1108–15. doi:10.​1002/​acr.​21663.CrossRef
15.
16.
go back to reference Leffers HC, Ostergaard M, Glintborg B, Krogh NS, Foged H, Tarp U, et al. Efficacy of abatacept and tocilizumab in patients with rheumatoid arthritis treated in clinical practice: results from the nationwide Danish DANBIO registry. Ann Rheum Dis. 2011;70(7):1216–22. doi:10.1136/ard.2010.140129.CrossRefPubMed Leffers HC, Ostergaard M, Glintborg B, Krogh NS, Foged H, Tarp U, et al. Efficacy of abatacept and tocilizumab in patients with rheumatoid arthritis treated in clinical practice: results from the nationwide Danish DANBIO registry. Ann Rheum Dis. 2011;70(7):1216–22. doi:10.​1136/​ard.​2010.​140129.CrossRefPubMed
17.
go back to reference Simard JF, Arkema EV, Sundstrom A, Geborek P, Saxne T, Baecklund E, et al. Ten years with biologics: to whom do data on effectiveness and safety apply? Rheumatology (Oxford). 2011;50(1):204–13. doi:10.1093/rheumatology/keq326.CrossRef Simard JF, Arkema EV, Sundstrom A, Geborek P, Saxne T, Baecklund E, et al. Ten years with biologics: to whom do data on effectiveness and safety apply? Rheumatology (Oxford). 2011;50(1):204–13. doi:10.​1093/​rheumatology/​keq326.CrossRef
18.
go back to reference Frazier-Mironer A, Dougados M, Mariette X, Cantagrel A, Deschamps V, Flipo RM, et al. Retention rates of adalimumab, etanercept and infliximab as first and second-line biotherapy in patients with rheumatoid arthritis in daily practice. Joint Bone Spine. 2014;81(4):352–9. doi:10.1016/j.jbspin.2014.02.014.CrossRefPubMed Frazier-Mironer A, Dougados M, Mariette X, Cantagrel A, Deschamps V, Flipo RM, et al. Retention rates of adalimumab, etanercept and infliximab as first and second-line biotherapy in patients with rheumatoid arthritis in daily practice. Joint Bone Spine. 2014;81(4):352–9. doi:10.​1016/​j.​jbspin.​2014.​02.​014.CrossRefPubMed
19.
go back to reference Nam JL, Ramiro S, Gaujoux-Viala C, Takase K, Leon-Garcia M, Emery P, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2014;73(3):516–28. doi:10.1136/annrheumdis-2013-204577.CrossRefPubMed Nam JL, Ramiro S, Gaujoux-Viala C, Takase K, Leon-Garcia M, Emery P, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2014;73(3):516–28. doi:10.​1136/​annrheumdis-2013-204577.CrossRefPubMed
20.
go back to reference Grijalva CG, Chung CP, Arbogast PG, Stein CM, Mitchel EF Jr, Griffin MR. Assessment of adherence to and persistence on disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. Med Care. 2007;45(10 Supl 2):S66–76. doi:10.1097/MLR.0b013e318041384c.CrossRefPubMed Grijalva CG, Chung CP, Arbogast PG, Stein CM, Mitchel EF Jr, Griffin MR. Assessment of adherence to and persistence on disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. Med Care. 2007;45(10 Supl 2):S66–76. doi:10.​1097/​MLR.​0b013e318041384c​.CrossRefPubMed
21.
go back to reference Tang B, Rahman M, Waters HC, Callegari P. Treatment persistence with adalimumab, etanercept, or infliximab in combination with methotrexate and the effects on health care costs in patients with rheumatoid arthritis. Clin Ther. 2008;30(7):1375–84.CrossRefPubMed Tang B, Rahman M, Waters HC, Callegari P. Treatment persistence with adalimumab, etanercept, or infliximab in combination with methotrexate and the effects on health care costs in patients with rheumatoid arthritis. Clin Ther. 2008;30(7):1375–84.CrossRefPubMed
22.
go back to reference Wu E, Chen L, Birnbaum H, Yang E, Cifaldi M. Retrospective claims data analysis of dosage adjustment patterns of TNF antagonists among patients with rheumatoid arthritis. Curr Med Res Opin. 2008;24(8):2229–40. doi:10.1185/03007990802229548.CrossRefPubMed Wu E, Chen L, Birnbaum H, Yang E, Cifaldi M. Retrospective claims data analysis of dosage adjustment patterns of TNF antagonists among patients with rheumatoid arthritis. Curr Med Res Opin. 2008;24(8):2229–40. doi:10.​1185/​0300799080222954​8.CrossRefPubMed
23.
go back to reference Curkendall S, Patel V, Gleeson M, Campbell RS, Zagari M, Dubois R. Compliance with biologic therapies for rheumatoid arthritis: do patient out-of-pocket payments matter? Arthritis Rheum. 2008;59(10):1519–26. doi:10.1002/art.24114.CrossRefPubMed Curkendall S, Patel V, Gleeson M, Campbell RS, Zagari M, Dubois R. Compliance with biologic therapies for rheumatoid arthritis: do patient out-of-pocket payments matter? Arthritis Rheum. 2008;59(10):1519–26. doi:10.​1002/​art.​24114.CrossRefPubMed
25.
go back to reference Yazici Y, Krasnokutsky S, Barnes JP, Hines PL, Wang J, Rosenblatt L. Changing patterns of tumor necrosis factor inhibitor use in 9074 patients with rheumatoid arthritis. J Rheumatol. 2009;36(5):907–13. doi:10.3899/jrheum.080592.CrossRefPubMed Yazici Y, Krasnokutsky S, Barnes JP, Hines PL, Wang J, Rosenblatt L. Changing patterns of tumor necrosis factor inhibitor use in 9074 patients with rheumatoid arthritis. J Rheumatol. 2009;36(5):907–13. doi:10.​3899/​jrheum.​080592.CrossRefPubMed
30.
go back to reference 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(5):625–39. doi:10.1002/acr.21641.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(5):625–39. doi:10.​1002/​acr.​21641.CrossRefPubMedPubMedCentral
32.
go back to reference Rendas-Baum R, Wallenstein GV, Koncz T, Kosinski M, Yang M, Bradley J, et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-alpha inhibitors. Arthritis Res Ther. 2011;13(1):R25. doi:10.1186/ar3249.CrossRefPubMedPubMedCentral Rendas-Baum R, Wallenstein GV, Koncz T, Kosinski M, Yang M, Bradley J, et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-alpha inhibitors. Arthritis Res Ther. 2011;13(1):R25. doi:10.​1186/​ar3249.CrossRefPubMedPubMedCentral
33.
go back to reference Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005;353(11):1114–23. doi:10.1056/NEJMoa050524.CrossRefPubMed Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005;353(11):1114–23. doi:10.​1056/​NEJMoa050524.CrossRefPubMed
34.
go back to reference Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54(9):2793–806. doi:10.1002/art.22025.CrossRefPubMed Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54(9):2793–806. doi:10.​1002/​art.​22025.CrossRefPubMed
35.
go back to reference Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven VR, Sanchez A, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008;67(11):1516–23. doi:10.1136/ard.2008.092932.CrossRefPubMed Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven VR, Sanchez A, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008;67(11):1516–23. doi:10.​1136/​ard.​2008.​092932.CrossRefPubMed
36.
go back to reference Burmester GR, Blanco R, Charles-Schoeman C, Wollenhaupt J, Zerbini C, Benda B, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. The Lancet. 2013;381(9865):451–60. doi:10.1016/s0140-6736(12)61424-x.CrossRef Burmester GR, Blanco R, Charles-Schoeman C, Wollenhaupt J, Zerbini C, Benda B, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. The Lancet. 2013;381(9865):451–60. doi:10.​1016/​s0140-6736(12)61424-x.CrossRef
37.
go back to reference van den Hoek J, Roorda LD, Boshuizen HC, van Hees J, Rupp I, Tijhuis GJ, et al. Long term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis: a longitudinal study. Arthritis Care Res (Hoboken). 2013;65:1157–65. doi:10.1002/acr.21950.CrossRefPubMed van den Hoek J, Roorda LD, Boshuizen HC, van Hees J, Rupp I, Tijhuis GJ, et al. Long term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis: a longitudinal study. Arthritis Care Res (Hoboken). 2013;65:1157–65. doi:10.​1002/​acr.​21950.CrossRefPubMed
38.
go back to reference Curtis JR, Chen L, Bharat A, Delzell E, Greenberg JD, Harrold L, et al. Linkage of a de-identified United States rheumatoid arthritis registry with administrative data to facilitate comparative effectiveness research. Arthritis Care Res (Hoboken). 2014;66(12):1790–8. doi:10.1002/acr.22377.CrossRefPubMedPubMedCentral Curtis JR, Chen L, Bharat A, Delzell E, Greenberg JD, Harrold L, et al. Linkage of a de-identified United States rheumatoid arthritis registry with administrative data to facilitate comparative effectiveness research. Arthritis Care Res (Hoboken). 2014;66(12):1790–8. doi:10.​1002/​acr.​22377.CrossRefPubMedPubMedCentral
Metadata
Title
Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA Registry
Authors
Vibeke Strand
Paul Miller
Setareh A. Williams
Katherine Saunders
Shannon Grant
Joel Kremer
Publication date
01-12-2017
Publisher
Springer Healthcare
Published in
Rheumatology and Therapy / Issue 2/2017
Print ISSN: 2198-6576
Electronic ISSN: 2198-6584
DOI
https://doi.org/10.1007/s40744-017-0078-y

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