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Published in: Arthritis Research & Therapy 1/2020

01-12-2020 | Rheumatoid Arthritis | Research article

Clinical predictors of multiple failure to biological therapy in patients with rheumatoid arthritis

Authors: Marta Novella-Navarro, Chamaida Plasencia, Carolina Tornero, Victoria Navarro-Compán, José L. Cabrera-Alarcón, Diana Peiteado-López, Laura Nuño, Irene Monjo-Henry, Karen Franco-Gómez, Alejandro Villalba, Alejandro Balsa

Published in: Arthritis Research & Therapy | Issue 1/2020

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Abstract

Background

Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians.

Objectives

This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure.

Methods

This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients).

Results

A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34–26.82) were independently associated with being MR-patients to bDMARDs.

Conclusions

In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.
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Literature
1.
2.
go back to reference Singh JA, Saag KG, Bridges SL, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1–26.PubMed Singh JA, Saag KG, Bridges SL, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1–26.PubMed
3.
go back to reference Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75:3–15.CrossRefPubMed Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75:3–15.CrossRefPubMed
4.
go back to reference Hetland ML, Christensen IJ, Tarp U, et al. Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum. 2010;62(1):22–32.CrossRefPubMed Hetland ML, Christensen IJ, Tarp U, et al. Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum. 2010;62(1):22–32.CrossRefPubMed
5.
go back to reference Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ, British Society for Rheumatology Biologics Register. Outcomes after switching from one antitumor 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.CrossRefPubMed Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ, British Society for Rheumatology Biologics Register. Outcomes after switching from one antitumor 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.CrossRefPubMed
6.
go back to reference González-Álvaro I, Ortiz AM, Seoane IV, García-Vicuña R, Martínez C, Gomariz RP. Biomarkers predicting a need for intensive treatment in patients with early arthritis. Curr Pharm Des. 2015;21:170–81.CrossRefPubMed González-Álvaro I, Ortiz AM, Seoane IV, García-Vicuña R, Martínez C, Gomariz RP. Biomarkers predicting a need for intensive treatment in patients with early arthritis. Curr Pharm Des. 2015;21:170–81.CrossRefPubMed
7.
go back to reference Maini RN, Breedveld FC, Kalden JR, Smolen JS, Furst D, Weisman MH, et al. Sustained improvement over two years in physical function, structural damage, and sings and symptoms among patients with rheumatoid arthritis treated with infliximab and metothrexate. Arthritis Rheum. 2004;50:1051–65.CrossRefPubMed Maini RN, Breedveld FC, Kalden JR, Smolen JS, Furst D, Weisman MH, et al. Sustained improvement over two years in physical function, structural damage, and sings and symptoms among patients with rheumatoid arthritis treated with infliximab and metothrexate. Arthritis Rheum. 2004;50:1051–65.CrossRefPubMed
8.
go back to reference Azteni F, Bongiovanni S, Marchesoni A, Filippini M, Caporali R, Gorla R, et al. Predictors of response to anti-TNF therapy in RA patients with moderate or high DAS28 scores. Joint Bone Spine. 2014;81:37–40.CrossRef Azteni F, Bongiovanni S, Marchesoni A, Filippini M, Caporali R, Gorla R, et al. Predictors of response to anti-TNF therapy in RA patients with moderate or high DAS28 scores. Joint Bone Spine. 2014;81:37–40.CrossRef
9.
go back to reference Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum. 2000;43:22–9.CrossRefPubMed Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum. 2000;43:22–9.CrossRefPubMed
10.
go back to reference Kearsley-Fleet L, Davies R, De Cock D, Watson KD, Lunt M, Buch MH, et al. Biologic refractory disease in rheumatoid arthritis: results from de British Society for Rheumatology Biologic Register for Rheumatoid Arthritis. Ann Rheum Dis. 2018;77:1405–12.CrossRefPubMed Kearsley-Fleet L, Davies R, De Cock D, Watson KD, Lunt M, Buch MH, et al. Biologic refractory disease in rheumatoid arthritis: results from de British Society for Rheumatology Biologic Register for Rheumatoid Arthritis. Ann Rheum Dis. 2018;77:1405–12.CrossRefPubMed
11.
go back to reference Bécède M, Alasti F, Gessl I, Haupt L, Kerschbaumer A, Landesmann U, et al. Risk profiling for a refractory course of rheumatoid arthritis. Seminars Arthritis Rheum. 2019;49:211–7.CrossRef Bécède M, Alasti F, Gessl I, Haupt L, Kerschbaumer A, Landesmann U, et al. Risk profiling for a refractory course of rheumatoid arthritis. Seminars Arthritis Rheum. 2019;49:211–7.CrossRef
12.
go back to reference Martínez-Feito A, Plasencia-Rodríguez C, Navarro-Compán V, Hernandez-Breijo B, González MA, Monjo I, et al. The effect of methotrexate versus other disease-modifying anti-rheumatic drugs on serum drug levels and clinical response in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors. Clin Rheumatol. 2019;38(3):949–95.CrossRefPubMed Martínez-Feito A, Plasencia-Rodríguez C, Navarro-Compán V, Hernandez-Breijo B, González MA, Monjo I, et al. The effect of methotrexate versus other disease-modifying anti-rheumatic drugs on serum drug levels and clinical response in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors. Clin Rheumatol. 2019;38(3):949–95.CrossRefPubMed
13.
go back to reference Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–24.CrossRefPubMed Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–24.CrossRefPubMed
14.
go back to reference Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 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 Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 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
15.
go back to reference De Hair MJH, Jacobs JWG, Schoneveld JLM, Van Laar JM. Difficult-to treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology. 2018;57:1135–44.PubMed De Hair MJH, Jacobs JWG, Schoneveld JLM, Van Laar JM. Difficult-to treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology. 2018;57:1135–44.PubMed
17.
go back to reference Favalli EG, Biggioggero M, Marchesoni A, Meroni PL. Survival on treatment with second-line biologic therapy: a cohort study comparing cycling and swap strategies. Rheumatology. 2014;53:1664–8.CrossRefPubMed Favalli EG, Biggioggero M, Marchesoni A, Meroni PL. Survival on treatment with second-line biologic therapy: a cohort study comparing cycling and swap strategies. Rheumatology. 2014;53:1664–8.CrossRefPubMed
18.
go back to reference Aletaha D, Funovits J, Keystone EC, Smolen JS. Disease activity early in the course of treatment predicts response to therapy after one year in rheumatoid arthritis patients. Arthritis Rheum. 2007;56:3226–35.CrossRefPubMed Aletaha D, Funovits J, Keystone EC, Smolen JS. Disease activity early in the course of treatment predicts response to therapy after one year in rheumatoid arthritis patients. Arthritis Rheum. 2007;56:3226–35.CrossRefPubMed
19.
go back to reference Finckh A, Ciurea A, Brulhart L, Möller B, Walker UA, Courvoisier D, et al. Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent? Ann Rheum Dis. 2010;69:387–93.CrossRefPubMed Finckh A, Ciurea A, Brulhart L, Möller B, Walker UA, Courvoisier D, et al. Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent? Ann Rheum Dis. 2010;69:387–93.CrossRefPubMed
20.
go back to reference Hamann PDH, Pauling JD, McHugh N, Hyrich K, Shaddick G. Early responses to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA. Rheumatologys. 2020;59(7):1709–14.CrossRef Hamann PDH, Pauling JD, McHugh N, Hyrich K, Shaddick G. Early responses to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA. Rheumatologys. 2020;59(7):1709–14.CrossRef
21.
go back to reference Smolen JS, Van Der Heide D, StClaire W, Emery P, Bathon JM, Keystone E, et al. Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum. 2006;54(3):702–10.CrossRefPubMed Smolen JS, Van Der Heide D, StClaire W, Emery P, Bathon JM, Keystone E, et al. Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum. 2006;54(3):702–10.CrossRefPubMed
22.
go back to reference Gwinnutt JM, Symmons DPM, MacGregor AJ, Chipping JR, Marshall T, Lunt M, et al. Twenty-year outcome and association between early treatment and mortality and disability in an inception cohort of patients with rheumatoid arthritis: results from the Norfolk arthritis register. Arthritis Rheumatol. 2017;69(8):1566–75.CrossRefPubMedPubMedCentral Gwinnutt JM, Symmons DPM, MacGregor AJ, Chipping JR, Marshall T, Lunt M, et al. Twenty-year outcome and association between early treatment and mortality and disability in an inception cohort of patients with rheumatoid arthritis: results from the Norfolk arthritis register. Arthritis Rheumatol. 2017;69(8):1566–75.CrossRefPubMedPubMedCentral
23.
go back to reference Roodenrijs NMT, de Hair MJH, Van der Goes MC, Jacobs JWG, Welsing PMJ, van der Heijde D, et al. Characteristics of difficult-to treat rheumatoid arthritis: a result of an international survey. Ann Rheum Dis. 2018;77:1705–9.CrossRefPubMed Roodenrijs NMT, de Hair MJH, Van der Goes MC, Jacobs JWG, Welsing PMJ, van der Heijde D, et al. Characteristics of difficult-to treat rheumatoid arthritis: a result of an international survey. Ann Rheum Dis. 2018;77:1705–9.CrossRefPubMed
24.
go back to reference Melville AR, Kearsley-Fleet L, Buch MH, Hyrich KL. Understanding refractory rheumatoid arthritis: implications for a therapeutic approach. Drugs. 2020;80(9):849–57.CrossRefPubMed Melville AR, Kearsley-Fleet L, Buch MH, Hyrich KL. Understanding refractory rheumatoid arthritis: implications for a therapeutic approach. Drugs. 2020;80(9):849–57.CrossRefPubMed
25.
go back to reference Hammer HB, Michelsen B, Provan SA, Sexton J, Lampa J, Uhlig T, et al. Tender joint count and inflammatory activity in patients with established rheumatoid arthritis: results from a longitudinal study. Arthritis Care Res (Hoboken). 2020;72(1):27–35.CrossRef Hammer HB, Michelsen B, Provan SA, Sexton J, Lampa J, Uhlig T, et al. Tender joint count and inflammatory activity in patients with established rheumatoid arthritis: results from a longitudinal study. Arthritis Care Res (Hoboken). 2020;72(1):27–35.CrossRef
26.
go back to reference Kristensen LE, Bliddal H, Christensen R, Karlsson JA, Gülfe A, Saxne T, et al. In swollen to tender joint count ratio a new and useful clinical marker for biologic drug response in rheumatoid arthritis? Results from a Swedish cohort. Arthritis Care Res (Hoboken). 2014;66(2):173–9.CrossRef Kristensen LE, Bliddal H, Christensen R, Karlsson JA, Gülfe A, Saxne T, et al. In swollen to tender joint count ratio a new and useful clinical marker for biologic drug response in rheumatoid arthritis? Results from a Swedish cohort. Arthritis Care Res (Hoboken). 2014;66(2):173–9.CrossRef
27.
go back to reference Balogh E, Madruga-Dias J, Orr C, Mullan R, Harty L, Firtgerald O, et al. Comparison of remission criteria in a tumour necrosis factor inhibitor treated rheumatoid arthritis longitudinal cohort: patient global health is a confounder. Arthritis Res Ther. 2013;15:R221.CrossRefPubMedPubMedCentral Balogh E, Madruga-Dias J, Orr C, Mullan R, Harty L, Firtgerald O, et al. Comparison of remission criteria in a tumour necrosis factor inhibitor treated rheumatoid arthritis longitudinal cohort: patient global health is a confounder. Arthritis Res Ther. 2013;15:R221.CrossRefPubMedPubMedCentral
Metadata
Title
Clinical predictors of multiple failure to biological therapy in patients with rheumatoid arthritis
Authors
Marta Novella-Navarro
Chamaida Plasencia
Carolina Tornero
Victoria Navarro-Compán
José L. Cabrera-Alarcón
Diana Peiteado-López
Laura Nuño
Irene Monjo-Henry
Karen Franco-Gómez
Alejandro Villalba
Alejandro Balsa
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2020
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-020-02354-1

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