Skip to main content
Top
Published in: Clinical Rheumatology 4/2017

Open Access 01-04-2017 | Original Article

Factors influencing the choice of first- and second-line biologic therapy for the treatment of rheumatoid arthritis: real-life data from the Italian LORHEN Registry

Authors: Sara Monti, Catherine Klersy, Roberto Gorla, Piercarlo Sarzi-Puttini, Fabiola Atzeni, Raffaele Pellerito, Enrico Fusaro, Giuseppe Paolazzi, Pier Andrea Rocchetta, Ennio Giulio Favalli, Antonio Marchesoni, Roberto Caporali

Published in: Clinical Rheumatology | Issue 4/2017

Login to get access

Abstract

According to international recommendations, the selection of the biologic disease modifying anti-rheumatic drug (bDMARD) for rheumatoid arthritis (RA) is mainly left to the clinician’s preference. We analyzed the real-life factors influencing the first-line choice or the switching strategy, focusing on the prescription of abatacept (ABA) or tocilizumab (TCZ) compared to TNFα inhibitors (TNFi). Patients enrolled in the Lombardy Rheumatology Network (LORHEN) Registry after January 1, 2010, when all considered bDMARD agents were available, were included. The population was divided into “first-” and “second-line” bDMARD. We included 1910 patients (first line n = 1264, second line n = 646). Age was higher in ABA or TCZ vs TNFi treated patients (p < 0.0001). Positive latent tuberculosis screening was associated with first-line ABA (p = 0.002). Methotrexate (MTX) combination therapy was lower in the TCZ group (p = 0.02). The type (dyslipidemia, hypertension, pulmonary disease) and the number of comorbidities influenced the choice towards ABA (p = 0.01). Multinomial logistic regression demonstrated that a second-line treatment, higher age, dyslipidemia, pulmonary disease, other comorbidities, and extra-articular RA manifestations were associated with ABA compared to TNFi. TCZ was associated with a second-line treatment, higher age, and more severe disease activity. Stopping the first bDMARD due to adverse events (AE) influenced the choice towards ABA. In real life, higher age and comorbidities influence the choice towards ABA and TCZ compared to TNFi. ABA was preferred in case of suspension of previous treatments due to AE. After failing a first-line TNFi, swapping to a different mechanism of action is more common.
Literature
1.
go back to reference Nam JL, Ramiro S, Gaujoux-Viala C et al (2014) 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 73(3):516–528CrossRefPubMed Nam JL, Ramiro S, Gaujoux-Viala C et al (2014) 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 73(3):516–528CrossRefPubMed
2.
go back to reference Schiff M, Weinblatt ME, Valente R et al (2014) Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis 73:86–94CrossRefPubMed Schiff M, Weinblatt ME, Valente R et al (2014) Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis 73:86–94CrossRefPubMed
3.
go back to reference Pierreisnard A, Issa N, Barnetche T, Richez C, Schaeverbeke T (2013) Meta-analysis of clinical and radiological efficacy of biologics in rheumatoid arthritis patients naive or inadequately responsive to methotrexate. Jt Bone Spine Rev Rhum 80:386–392CrossRef Pierreisnard A, Issa N, Barnetche T, Richez C, Schaeverbeke T (2013) Meta-analysis of clinical and radiological efficacy of biologics in rheumatoid arthritis patients naive or inadequately responsive to methotrexate. Jt Bone Spine Rev Rhum 80:386–392CrossRef
4.
go back to reference Favalli EG, Bugatti S, Biggioggero M, Caporali R (2014) Treatment comparison in rheumatoid arthritis: head-to-head trials and innovative study designs. Biomed Res Int 2014:831603CrossRefPubMedPubMedCentral Favalli EG, Bugatti S, Biggioggero M, Caporali R (2014) Treatment comparison in rheumatoid arthritis: head-to-head trials and innovative study designs. Biomed Res Int 2014:831603CrossRefPubMedPubMedCentral
5.
go back to reference Jobanputra P, Maggs F, Deeming A, et al. (2012) A randomised efficacy and discontinuation study of etanercept versus adalimumab (RED SEA) for rheumatoid arthritis: a pragmatic, unblinded, non-inferiority study of first TNF inhibitor use: outcomes over 2 years. BMJ Open 2(6) Jobanputra P, Maggs F, Deeming A, et al. (2012) A randomised efficacy and discontinuation study of etanercept versus adalimumab (RED SEA) for rheumatoid arthritis: a pragmatic, unblinded, non-inferiority study of first TNF inhibitor use: outcomes over 2 years. BMJ Open 2(6)
6.
go back to reference Gabay C, Emery P, van Vollenhoven R et al (2013) Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet 381(9877):1541–1550CrossRefPubMed Gabay C, Emery P, van Vollenhoven R et al (2013) Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet 381(9877):1541–1550CrossRefPubMed
7.
go back to reference Smolen JS, Landewé R, Breedveld FC et al (2014) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 73:492–509CrossRefPubMed Smolen JS, Landewé R, Breedveld FC et al (2014) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 73:492–509CrossRefPubMed
8.
go back to reference Caporali R, Sarzi-Puttini P, Atzeni F et al (2010) Switching TNF-alpha antagonists in rheumatoid arthritis: the experience of the LORHEN registry. Autoimmun Rev 9:465–469CrossRefPubMed Caporali R, Sarzi-Puttini P, Atzeni F et al (2010) Switching TNF-alpha antagonists in rheumatoid arthritis: the experience of the LORHEN registry. Autoimmun Rev 9:465–469CrossRefPubMed
9.
go back to reference Singh JA, Saag KG, Bridges SL, et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol Singh JA, Saag KG, Bridges SL, et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol
10.
go back to reference Tanaka Y, Kubo S, Yamanaka H et al (2014) Efficacy and safety of abatacept in routine care of patients with rheumatoid arthritis: Orencia® as Biological Intensive Treatment for RA (ORBIT) study. Mod Rheumatol 24:754–762CrossRefPubMed Tanaka Y, Kubo S, Yamanaka H et al (2014) Efficacy and safety of abatacept in routine care of patients with rheumatoid arthritis: Orencia® as Biological Intensive Treatment for RA (ORBIT) study. Mod Rheumatol 24:754–762CrossRefPubMed
11.
go back to reference Yun H, Xie F, Delzell E, Levitan EB et al (2016) Comparative risk of hospitalized infection associated with biologic agents in rheumatoid arthritis patients enrolled in Medicare. Arthritis Rheumatol Hoboken NJ 68:56–66CrossRef Yun H, Xie F, Delzell E, Levitan EB et al (2016) Comparative risk of hospitalized infection associated with biologic agents in rheumatoid arthritis patients enrolled in Medicare. Arthritis Rheumatol Hoboken NJ 68:56–66CrossRef
12.
go back to reference Cantini F, Niccoli L, Nannini C, et al. (2015) Tailored first-line biologic therapy in patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis. Semin Arthritis Rheum Cantini F, Niccoli L, Nannini C, et al. (2015) Tailored first-line biologic therapy in patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis. Semin Arthritis Rheum
13.
go back to reference Sarzi-Puttini P, Antivalle M, Marchesoni A et al (2008) Efficacy and safety of anti-TNF agents in the Lombardy rheumatoid arthritis network (LORHEN). Reumatismo 60:290–295PubMed Sarzi-Puttini P, Antivalle M, Marchesoni A et al (2008) Efficacy and safety of anti-TNF agents in the Lombardy rheumatoid arthritis network (LORHEN). Reumatismo 60:290–295PubMed
14.
go back to reference van den Broek M, Lems WF, Allaart CF (2012) Do we need guidelines to stop as well as to start biological therapies for rheumatoid arthritis? Clin Exp Rheumatol 30(4 Suppl 73):S21–S26PubMed van den Broek M, Lems WF, Allaart CF (2012) Do we need guidelines to stop as well as to start biological therapies for rheumatoid arthritis? Clin Exp Rheumatol 30(4 Suppl 73):S21–S26PubMed
15.
go back to reference Tanaka Y, Hirata S (2013) Is it possible to withdraw biologics from therapy in rheumatoid arthritis? Clin Ther 35:2028–2035CrossRefPubMed Tanaka Y, Hirata S (2013) Is it possible to withdraw biologics from therapy in rheumatoid arthritis? Clin Ther 35:2028–2035CrossRefPubMed
16.
go back to reference Moghadam MG, Vonkeman HE, Ten Klooster PM, et al. (2016) Stopping tumor necrosis factor-inhibitors in patients with established rheumatoid arthritis in remission or stable low disease activity: a pragmatic randomized multicenter open-label controlled trial. Arthritis Rheumatol Hoboken NJ Moghadam MG, Vonkeman HE, Ten Klooster PM, et al. (2016) Stopping tumor necrosis factor-inhibitors in patients with established rheumatoid arthritis in remission or stable low disease activity: a pragmatic randomized multicenter open-label controlled trial. Arthritis Rheumatol Hoboken NJ
17.
go back to reference Radovits BJ, Fransen J, Eijsbouts A, van Riel PLCM, Laan RFJM (2009) Missed opportunities in the treatment of elderly patients with rheumatoid arthritis. Rheumatology 48:906–910CrossRefPubMed Radovits BJ, Fransen J, Eijsbouts A, van Riel PLCM, Laan RFJM (2009) Missed opportunities in the treatment of elderly patients with rheumatoid arthritis. Rheumatology 48:906–910CrossRefPubMed
18.
go back to reference Morsley K, Kilner T, Steuer A (2015) Biologics prescribing for rheumatoid arthritis in older patients: a single-center retrospective cross-sectional study. Rheumatol Ther 2:165–172CrossRefPubMedPubMedCentral Morsley K, Kilner T, Steuer A (2015) Biologics prescribing for rheumatoid arthritis in older patients: a single-center retrospective cross-sectional study. Rheumatol Ther 2:165–172CrossRefPubMedPubMedCentral
19.
go back to reference Martin WJ, Shim M, Paulus HE et al (2014) Older age at rheumatoid arthritis onset and comorbidities correlate with less health assessment questionnaire-disability index and clinical disease activity index response to etanercept in the RADIUS 2 registry. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis 20:301–305 Martin WJ, Shim M, Paulus HE et al (2014) Older age at rheumatoid arthritis onset and comorbidities correlate with less health assessment questionnaire-disability index and clinical disease activity index response to etanercept in the RADIUS 2 registry. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis 20:301–305
20.
go back to reference Sugihara T, Harigai M (2016) Targeting low disease activity in elderly-onset rheumatoid arthritis: current and future roles of biological disease-modifying antirheumatic drugs. Drugs Aging 33:97–107CrossRefPubMedPubMedCentral Sugihara T, Harigai M (2016) Targeting low disease activity in elderly-onset rheumatoid arthritis: current and future roles of biological disease-modifying antirheumatic drugs. Drugs Aging 33:97–107CrossRefPubMedPubMedCentral
21.
go back to reference Zhang J, Xie F, Yun H, et al. (2016) Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis. Ann Rheum Dis Zhang J, Xie F, Yun H, et al. (2016) Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis. Ann Rheum Dis
22.
go back to reference Crepaldi G, Scirè CA, Carrara G et al (2016) Cardiovascular comorbidities relate more than others with disease activity in rheumatoid arthritis. PLoS One 11:e0146991CrossRefPubMedPubMedCentral Crepaldi G, Scirè CA, Carrara G et al (2016) Cardiovascular comorbidities relate more than others with disease activity in rheumatoid arthritis. PLoS One 11:e0146991CrossRefPubMedPubMedCentral
23.
go back to reference Kroot EJ, van Gestel AM, Swinkels HL, Albers MM, van de Putte LB, van Riel PL (2001) Chronic comorbidity in patients with early rheumatoid arthritis: a descriptive study. J Rheumatol 28:1511–1517PubMed Kroot EJ, van Gestel AM, Swinkels HL, Albers MM, van de Putte LB, van Riel PL (2001) Chronic comorbidity in patients with early rheumatoid arthritis: a descriptive study. J Rheumatol 28:1511–1517PubMed
24.
25.
go back to reference Dougados M, Soubrier M, Antunez A et al (2014) Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis 73:62–68CrossRefPubMed Dougados M, Soubrier M, Antunez A et al (2014) Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis 73:62–68CrossRefPubMed
26.
go back to reference Iqbal K, Kelly C (2015) Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review. Ther Adv Musculoskelet Dis 7:247–267CrossRefPubMedPubMedCentral Iqbal K, Kelly C (2015) Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review. Ther Adv Musculoskelet Dis 7:247–267CrossRefPubMedPubMedCentral
27.
28.
go back to reference Marino S, Sud D, Plessner H, et al. (2007) Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue. PLoS Comput Biol [Internet] 3(10) Marino S, Sud D, Plessner H, et al. (2007) Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue. PLoS Comput Biol [Internet] 3(10)
29.
go back to reference Alten R, Kaine J, Keystone E, Nash P, Delaet I, Genovese MC (2014) Long-term safety of subcutaneous abatacept in rheumatoid arthritis: integrated analysis of clinical trial data representing more than four years of treatment. Arthritis Rheumatol Hoboken NJ 66:1987–1997CrossRef Alten R, Kaine J, Keystone E, Nash P, Delaet I, Genovese MC (2014) Long-term safety of subcutaneous abatacept in rheumatoid arthritis: integrated analysis of clinical trial data representing more than four years of treatment. Arthritis Rheumatol Hoboken NJ 66:1987–1997CrossRef
30.
go back to reference Schiff M, Keiserman M, Codding C et al (2008) Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis 67:1096–1103CrossRefPubMed Schiff M, Keiserman M, Codding C et al (2008) Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis 67:1096–1103CrossRefPubMed
31.
go back to reference Salliot C, Dougados M, Gossec L (2009) Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials. Ann Rheum Dis 68:25–32CrossRefPubMed Salliot C, Dougados M, Gossec L (2009) Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials. Ann Rheum Dis 68:25–32CrossRefPubMed
32.
go back to reference Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ et al (2010) Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 69:88–96CrossRefPubMed Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ et al (2010) Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 69:88–96CrossRefPubMed
33.
go back to reference Buckley F, Finckh A, Huizinga TWJ, Dejonckheere F, Jansen JP (2015) Comparative efficacy of novel DMARDs as monotherapy and in combination with methotrexate in rheumatoid arthritis patients with inadequate response to conventional DMARDs: a network meta-analysis. J Manag Care Spec Pharm 21:409–423CrossRefPubMed Buckley F, Finckh A, Huizinga TWJ, Dejonckheere F, Jansen JP (2015) Comparative efficacy of novel DMARDs as monotherapy and in combination with methotrexate in rheumatoid arthritis patients with inadequate response to conventional DMARDs: a network meta-analysis. J Manag Care Spec Pharm 21:409–423CrossRefPubMed
34.
go back to reference Gabay C, Riek M, Hetland ML, et al. (2015) Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: results from a European collaborative study. Ann Rheum Dis Gabay C, Riek M, Hetland ML, et al. (2015) Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: results from a European collaborative study. Ann Rheum Dis
35.
go back to reference Favalli EG, Biggioggero M, Marchesoni A, Meroni PL (2014) Survival on treatment with second-line biologic therapy: a cohort study comparing cycling and swap strategies. Rheumatol Oxf Engl 53:1664–1668CrossRef Favalli EG, Biggioggero M, Marchesoni A, Meroni PL (2014) Survival on treatment with second-line biologic therapy: a cohort study comparing cycling and swap strategies. Rheumatol Oxf Engl 53:1664–1668CrossRef
36.
go back to reference Lee YH, Bae S-C (2015) Comparative efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with active rheumatoid arthritis that inadequately responds to tumor necrosis factor inhibitors: a Bayesian network meta-analysis of randomized controlled trials. Int J Rheum Dis Lee YH, Bae S-C (2015) Comparative efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with active rheumatoid arthritis that inadequately responds to tumor necrosis factor inhibitors: a Bayesian network meta-analysis of randomized controlled trials. Int J Rheum Dis
Metadata
Title
Factors influencing the choice of first- and second-line biologic therapy for the treatment of rheumatoid arthritis: real-life data from the Italian LORHEN Registry
Authors
Sara Monti
Catherine Klersy
Roberto Gorla
Piercarlo Sarzi-Puttini
Fabiola Atzeni
Raffaele Pellerito
Enrico Fusaro
Giuseppe Paolazzi
Pier Andrea Rocchetta
Ennio Giulio Favalli
Antonio Marchesoni
Roberto Caporali
Publication date
01-04-2017
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 4/2017
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-016-3528-y

Other articles of this Issue 4/2017

Clinical Rheumatology 4/2017 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.