Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis.
Abatacept
American college of rheumatology
Meta-regression
Network meta-analysis
Rheumatoid arthritis
Rituximab
Tocilizumab
bDMARD
Journal
Advances in rheumatology (London, England)
ISSN: 2523-3106
Titre abrégé: Adv Rheumatol
Pays: England
ID NLM: 101734172
Informations de publication
Date de publication:
06 07 2023
06 07 2023
Historique:
received:
05
04
2022
accepted:
10
04
2023
medline:
10
7
2023
pubmed:
7
7
2023
entrez:
6
7
2023
Statut:
epublish
Résumé
Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.
Sections du résumé
BACKGROUND
Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents.
METHODS
We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response.
RESULTS
The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab.
CONCLUSION
We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.
Identifiants
pubmed: 37415193
doi: 10.1186/s42358-023-00298-z
pii: 10.1186/s42358-023-00298-z
doi:
Substances chimiques
Abatacept
7D0YB67S97
Rituximab
4F4X42SYQ6
Methotrexate
YL5FZ2Y5U1
tocilizumab
I031V2H011
Tumor Necrosis Factor Inhibitors
0
Antirheumatic Agents
0
Types de publication
Meta-Analysis
Systematic Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
30Subventions
Organisme : FAPESP
ID : 2019/09068-3
Organisme : CNPq
ID : 437413/2018-7
Informations de copyright
© 2023. The Author(s).
Références
Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010;376:1094–108.
doi: 10.1016/S0140-6736(10)60826-4
pubmed: 20870100
Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ, British Society for Rheumatology Biologics Register. 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;56:13–20.
doi: 10.1002/art.22331
pubmed: 17195186
Kavanaugh A, Rosengren S, Lee SJ, Hammaker D, Firestein GS, Kalunian K, et al. Assessment of rituximab’s immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results. Ann Rheum Dis. 2008;67:402–8.
doi: 10.1136/ard.2007.074229
pubmed: 17644541
Moreland LW, Alten R, Van den Bosch F, Appelboom T, Leon M, Emery P, et al. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum. 2002;46:1470–9.
doi: 10.1002/art.10294
pubmed: 12115176
Keystone EC, Anisfeld A, Ogale S, Devenport JN, Curtis JR. Continued benefit of tocilizumab plus disease-modifying antirheumatic drug therapy in patients with rheumatoid arthritis and inadequate clinical responses by week 8 of treatment. J Rheumatol. 2014;41:216–26.
doi: 10.3899/jrheum.130489
pubmed: 24429164
Salliot C, Finckh A, Katchamart W, Lu Y, Sun Y, Bombardier C, et al. Indirect comparisons of the efficacy of biological antirheumatic agents in rheumatoid arthritis in patients with an inadequate response to conventional disease-modifying antirheumatic drugs or to an anti-tumour necrosis factor agent: a meta-analysis. Ann Rheum Dis. 2011;70:266–71.
doi: 10.1136/ard.2010.132134
pubmed: 21097801
Bergman GJ, Hochberg MC, Boers M, Wintfeld N, Kielhorn A, Jansen JP. Indirect comparison of tocilizumab and other biologic agents in patients with rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs. Semin Arthritis Rheum. 2010;39:425–41.
doi: 10.1016/j.semarthrit.2009.12.002
pubmed: 20223500
Schoels M, Aletaha D, Smolen JS, Wong JB. Comparative effectiveness and safety of biological treatment options after tumour necrosis factor α inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis. Ann Rheum Dis. 2012;71:1303–8.
doi: 10.1136/annrheumdis-2011-200490
pubmed: 22294630
Stevenson M, Archer R, Tosh J, Simpson E, Everson-Hock E, Stevens J, et al. Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation. Health Technol Assess. 2016;20:1–610.
pubmed: 27801641
pmcid: 5107884
Singh JA, Wells GA, Christensen R, Tanjong Ghogomu E, Maxwell L, Macdonald JK, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2011:CD008794.
pubmed: 21328309
pmcid: 7173749
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71 .
doi: 10.1136/bmj.n71
pubmed: 33782057
pmcid: 8005924
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd. etal 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69:1580–8.
doi: 10.1136/ard.2010.138461
pubmed: 20699241
Ward MM, Guthrie LC, Alba MI. Brief report: rheumatoid arthritis response criteria and patient-reported improvement in arthritis activity: is an American College of Rheumatology twenty percent response meaningful to patients? Arthritis Rheumatol. 2014;66:2339–43.
doi: 10.1002/art.38705
pubmed: 24838475
pmcid: 4146735
Brasil. Ministério da Saúde. Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Ciência e Tecnologia. Diretrizes Metodológicas. Sistema GRADE – manual de graduação da qualidade da evidência e força de recomendação para tomada de decisão em saúde. Brasília: Ministério da Saúde; 2014. http://bvsms.saude.gov.br/bvs/publicacoes/diretrizes_metodologicas_sistema_grade.pdf
Higgins JPT, Altman DG, Sterne JAC. Assessing risk of bias in included studies. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 (updated March 2011), The Cochrane Collaboration, Chichester (UK); 2011.
Dias S, Sutton AJ, Ades AE, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making. 2013;33:607–17.
doi: 10.1177/0272989X12458724
pubmed: 23104435
pmcid: 3704203
Brooks SP, Gelman A. General methods for monitoring convergence of iterative simulations. J Comput Graph Stat. 1998;7:34–55.
Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Stat Med. 2010;29:932–44.
doi: 10.1002/sim.3767
pubmed: 20213715
R Core Team (2022). R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/ .
Schiff M, Weinblatt ME, Valente R, van der Heijde D, Citera G, Elegbe A, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014;73:86–94.
doi: 10.1136/annrheumdis-2013-203843
pubmed: 23962455
Genovese MC, Schiff M, Luggen M, Le Bars M, Aranda R, Elegbe A, et al. Longterm safety and efficacy of abatacept through 5 years of treatment in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor inhibitor therapy. J Rheumatol. 2012;39:1546–54.
doi: 10.3899/jrheum.111531
pubmed: 22798265
Schiff M, Keiserman M, Codding C, Songcharoen S, Berman A, Nayiager S, et al. Clinical response and tolerability to abatacept in patients with rheumatoid arthritis previously treated with infliximab or abatacept: open-label extension of the ATTEST Study. Ann Rheum Dis. 2011;70:2003–7.
doi: 10.1136/annrheumdis-2011-200316
pubmed: 21914628
Gaultney J, Benucci M, Iannazzo S, Nappi C, Sion K, Sabater FJ. Trial-based cost-effectiveness of abatacept for rheumatoid arthritis patients in Italy. Expert Rev Pharmacoecon Outcomes Res. 2016;16:409–17.
doi: 10.1586/14737167.2016.1102636
pubmed: 26495961
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;353:1114–23.
doi: 10.1056/NEJMoa050524
pubmed: 16162882
Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006;144:865–76.
doi: 10.7326/0003-4819-144-12-200606200-00003
pubmed: 16785475
Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A, et al. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum. 2006;54:1390–400.
doi: 10.1002/art.21778
pubmed: 16649186
Porter D, van Melckebeke J, Dale J, Messow CM, McConnachie A, Walker A, et al. Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial. Lancet. 2016;388:239–47.
doi: 10.1016/S0140-6736(16)00380-9
pubmed: 27197690
Keystone E, Burmester GR, Furie R, Loveless JE, Emery P, Kremer J, et al. Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Arthritis Rheum. 2008;59:785–93.
doi: 10.1002/art.23715
pubmed: 18512710
Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, et al. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010;69:1629–35.
doi: 10.1136/ard.2009.119933
pubmed: 20488885
Mease PJ, Cohen S, Gaylis NB, Chubick A, Kaell AT, Greenwald M, et al. Efficacy and safety of retreatment in patients with rheumatoid arthritis with previous inadequate response to tumor necrosis factor inhibitors: results from the SUNRISE trial. J Rheumatol. 2010;37:917–27.
doi: 10.3899/jrheum.090442
pubmed: 20194448
Brown S, Everett CC, Naraghi K, Davies C, Dawkins B, Hulme C, McCabe C, Pavitt S, Emery P, Sharples L, Buch MH. Alternative tumour necrosis factor inhibitors (TNFi) or abatacept or rituximab following failure of initial TNFi in rheumatoid arthritis: the SWITCH RCT. Health Technol Assess. 2018;22:1–280.
pubmed: 30040065
pmcid: 6077599
Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013;381:1541–50.
doi: 10.1016/S0140-6736(13)60250-0
pubmed: 23515142
Bijlsma JWJ, Welsing PMJ, Woodworth TG, Middelink LM, Pethö-Schramm A, Bernasconi C, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016;388:343–55.
doi: 10.1016/S0140-6736(16)30363-4
pubmed: 27287832
Kivitz A, Olech E, Borofsky M, Zazueta BM, Navarro-Sarabia F, et al. Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. Arthritis Care Res. 2014;66:1653–61.
doi: 10.1002/acr.22384
Lindegaard HM, Johansen P, Gröndal G, Jensen EC, Juul L, Schlemmer AM, Agular B, Hansen I. Doubling the single-dose infusion rate of tocilizumab in rheumatoid arthritis is safe and efficacious. Scand J Rheumatol. 2016;45:262–6.
doi: 10.3109/03009742.2015.1112030
pubmed: 26727655
Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R, OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371:987–97.
doi: 10.1016/S0140-6736(08)60453-5
pubmed: 18358926
Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J. 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;67:1516–23.
doi: 10.1136/ard.2008.092932
pubmed: 18625622
Gottenberg JE, Morel J, Perrodeau E, Bardin T, Combe B, Dougados M, et al. Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study. BMJ. 2019;364:l67.
doi: 10.1136/bmj.l67
pubmed: 30679233
pmcid: 6344892
Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials - a practical guide with flowcharts. BMC Med Res Methodol. 2017;17:162.
doi: 10.1186/s12874-017-0442-1
pubmed: 29207961
pmcid: 5717805
Fischhoff B. The realities of risk-cost-benefit analysis. Science. 2015;350:aaa6516.
doi: 10.1126/science.aaa6516
pubmed: 26516286
Briggs AH, O’Brien BJ. The death of cost-minimization analysis? Health Econ. 2001;10:179–84.
doi: 10.1002/hec.584
pubmed: 11252048
Ades AE, Lu G, Higgins JP. The interpretation of random-effects meta-analysis in decision models. Med Decis Making. 2005;25:646–54.
doi: 10.1177/0272989X05282643
pubmed: 16282215
Dias S, Sutton AJ, Welton NJ, Ades AE. Evidence synthesis for decision making 3: heterogeneity–subgroups, meta-regression, bias, and bias-adjustment. Med Decis Making. 2013;33:618–40.
doi: 10.1177/0272989X13485157
pubmed: 23804507
pmcid: 3704206