Generic placeholder image

Current Rheumatology Reviews

Editor-in-Chief

ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Systematic Review Article

The Gap in Knowledge about Tapering Targeted Therapy being used as Monotherapy in Rheumatoid Arthritis: A Systematic Review

Author(s): Charis F. Meng*, Diviya A. Rajesh, Deanna P. Jannat-Khat, Bridget Jivanelli and Vivian Bykerk

Volume 20, Issue 1, 2024

Published on: 20 September, 2023

Page: [46 - 56] Pages: 11

DOI: 10.2174/1573397119666230828160108

Price: $65

Abstract

Background: Up to 30% of patients with RA are being treated with biologic (b)-disease modifying anti-rheumatic drugs (DMARDs) as monotherapy. Monotherapy with Interleukin (IL)-6 inhibitors(i) and Janus-kinase (JAK)-i has been shown to be effective. Whether patients can taper targeted therapy (bDMARDs and JAK-i) used as monotherapy (targeted monotherapy) is unknown.

Objective: To determine the feasibility of tapering of targeted monotherapy in patients with controlled RA.

Methods: We conducted a literature search in Medline, Embase and Cochrane Library for prospective studies reporting remission outcomes after tapering targeted monotherapy in RA patients, from 1/2014 - 8 /2021.

Results: 5 randomized studies which met our inclusion criteria, evaluating tapering of monotherapy with tumor necrosis factor-inhibitors, tocilizumab, abatacept and baricitinib in RA. Studies were heterogeneous. Three trials studied early RA. Three studies gradually tapered therapy, including 1 dose reduction study. Three studies tapered both biological and conventional-synthetic (cs)-DMARDs. No study compared stopping targeted monotherapy to continuing it. Remission rates were low 14-28% across all studies that stopped targeted monotherapy. The highest remission rate of 72% was reported by the dose reduction study. Trials that studied early RA reported remission rates after tapering ranging 27-72%. Trials tapering therapy in established RA reported rates of remission from 14-20%.

Conclusion: There is a crucial gap in published literature to inform on tapering targeted monotherapy in patients with RA. Stopping targeted monotherapy is unlikely to maintain disease control in RA. Dose reduction strategies and early treatment of disease may be associated with more successful tapering, and warrant future study.

Keywords: Rheumatoid arthritis, tapering, withdrawal, biological therapy, targeted therapy, monotherapy.

Graphical Abstract
[1]
Harrold LR, Briesacher BA, Peterson D, et al. Cost-related medication nonadherence in older patients with rheumatoid arthritis. J Rheumatol 2013; 40(2): 137-43.
[http://dx.doi.org/10.3899/jrheum.120441] [PMID: 23322458]
[2]
Harley CR, Frytak JR, Tandon N. Treatment compliance and dosage administration among rheumatoid arthritis patients receiving infliximab, etanercept, or methotrexate. Am J Manag Care 2003; 9(S6): S136-43.
[PMID: 14577718]
[3]
Shaw Y, Metes ID, Michaud K, et al. Rheumatoid arthritis patients’ motivations for accepting or resisting disease-modifying antirheumatic drug treatment regimens. Arthritis Care Res (Hoboken) 2018; 70(4): 533-41.
[http://dx.doi.org/10.1002/acr.23301] [PMID: 28575542]
[4]
Chen DY, Lau CS, Elzorkany B, et al. Dosing down and then discontinuing biologic therapy in rheumatoid arthritis: A review of the literature. Int J Rheum Dis 2018; 21(2): 362-72.
[http://dx.doi.org/10.1111/1756-185X.13238] [PMID: 29205904]
[5]
Verhoef LM, van den Bemt BJF, van der Maas A, et al. Down-titration and discontinuation strategies of tumour necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity. Cochrane Libr 2019; 2019(6): CD010455.
[http://dx.doi.org/10.1002/14651858.CD010455.pub3] [PMID: 31125448]
[6]
Cavalli G, Favalli eg. Biologic discontinuation strategies and outcomes in patients with rheumatoid arthritis. Expert Rev Clin Immunol 2019; 15(12): 1313-22.
[http://dx.doi.org/10.1080/1744666X.2020.1686976] [PMID: 31663390]
[7]
Yoshida K, Sung YK, Kavanaugh A, et al. Biologic discontinuation studies: A systematic review of methods. Ann Rheum Dis 2014; 73(3): 595-9.
[http://dx.doi.org/10.1136/annrheumdis-2013-203302] [PMID: 23723316]
[8]
Choy E, Aletaha D, Behrens F, et al. Monotherapy with biologic disease-modifying anti-rheumatic drugs in rheumatoid arthritis. Rheumatology 2017; 56(5): 689-97.
[PMID: 27550301]
[9]
Emery P, Sebba A, Huizinga TWJ. Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis. Ann Rheum Dis 2013; 72(12): 1897-904.
[http://dx.doi.org/10.1136/annrheumdis-2013-203485] [PMID: 23918035]
[10]
Detert J, Klaus P. Biologic monotherapy in the treatment of rheumatoid arthritis. Biologics 2015; 9: 35-43.
[PMID: 26028960]
[11]
Meng CF, Rajesh DA, Jannat-Khah DP, Jivanelli B, Bykerk VP. Can patients with controlled rheumatoid arthritis taper methotrexate from targeted therapy and sustain remission? A systematic review and metaanalysis. J Rheumatol 2023; 50(1): 36-47.
[http://dx.doi.org/10.3899/jrheum.220152] [PMID: 35970524]
[12]
Fraenkel L, Bathon JM, England BR, et al. 2021 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res 2021; 73(7): 924-39.
[http://dx.doi.org/10.1002/acr.24596] [PMID: 34101387]
[13]
Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020; 79(6): 685-99.
[http://dx.doi.org/10.1136/annrheumdis-2019-216655] [PMID: 31969328]
[14]
Julian PT. Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) 2022. Available from: https://www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2 (Accessed on: August 11, 2021).
[15]
Kaneko Y, Kato M, Tanaka Y, et al. Tocilizumab discontinuation after attaining remission in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate: results from a prospective randomised controlled study (the second year of the SURPRISE study). Ann Rheum Dis 2018; 77(9): 1268-75.
[http://dx.doi.org/10.1136/annrheumdis-2018-213416] [PMID: 29853455]
[16]
Bijlsma JWJ, Welsing PMJ, Woodworth TG, 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(10042): 343-55.
[http://dx.doi.org/10.1016/S0140-6736(16)30363-4] [PMID: 27287832]
[17]
van Mulligen E, Weel AE, Hazes JM, van der Helm-van Mil A, de Jong PHP. Tapering towards DMARD-free remission in established rheumatoid arthritis: 2-year results of the TARA trial. Ann Rheum Dis 2020; 79(9): 1174-81.
[http://dx.doi.org/10.1136/annrheumdis-2020-217485] [PMID: 32482645]
[18]
Emery P, Burmester GR, Bykerk VP, et al. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: Results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis 2015; 74(1): 19-26.
[http://dx.doi.org/10.1136/annrheumdis-2014-206106] [PMID: 25367713]
[19]
Takeuchi T, Genovese MC, Haraoui B, et al. Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: Results of a prospective study. Ann Rheum Dis 2019; 78(2): 171-8.
[http://dx.doi.org/10.1136/annrheumdis-2018-213271] [PMID: 30194275]
[20]
Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Maldonado MA. Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study. RMD open 2019; 5(1): e000840.
[21]
Tweehuysen L, van den Ende CH, Beeren FMM, Been EMJ, van den Hoogen FHJ, den Broeder AA. Little evidence for usefulness of biomarkers for predicting successful dose reduction or discontinuation of a biologic agent in rheumatoid arthritis: A systematic review. Arthritis Rheumatol 2017; 69(2): 301-8.
[http://dx.doi.org/10.1002/art.39946] [PMID: 27696778]
[22]
Tanaka Y, Oba K, Koike T, et al. Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: The RRRR study, a randomised controlled trial. Ann Rheum Dis 2020; 79(1): 94-102.
[http://dx.doi.org/10.1136/annrheumdis-2019-216169] [PMID: 31630117]
[23]
Tanaka Y, Atsumi T, Yamamoto K, et al. Factors associated with successful discontinuation of certolizumab pegol in early rheumatoid arthritis. Int J Rheum Dis 2020; 23(3): 316-24.
[http://dx.doi.org/10.1111/1756-185X.13780] [PMID: 31957303]
[24]
Tanaka Y, Hirata S, Kubo S, et al. Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study. Ann Rheum Dis 2015; 74(2): 389-95.
[http://dx.doi.org/10.1136/annrheumdis-2013-204016] [PMID: 24288014]
[25]
van Vollenhoven RF, Østergaard M, Leirisalo-Repo M, et al. Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis. Ann Rheum Dis 2016; 75(1): 52-8.
[http://dx.doi.org/10.1136/annrheumdis-2014-205726] [PMID: 25873634]
[26]
Emery P, Burmester GR, Naredo E, et al. Adalimumab dose tapering in patients with rheumatoid arthritis who are in long-standing clinical remission: Results of the phase IV PREDICTRA study. Ann Rheum Dis 2020; 79(8): 1023-30.
[PMID: 32404343]
[27]
Kuijper TM, Lamers-Karnebeek FBG, Jacobs JWG, Hazes JMW, Luime JJ. Flare rate in patients with rheumatoid arthritis in low disease activity or remission when tapering or stopping synthetic or biologic DMARD: A systematic review. J Rheumatol 2015; 42(11): 2012-22.
[http://dx.doi.org/10.3899/jrheum.141520] [PMID: 26428204]
[28]
Mangoni AA, Al Okaily F, Almoallim H, Al Rashidi S, Mohammed RHA, Barbary A. Relapse rates after elective discontinuation of anti-TNF therapy in rheumatoid arthritis: A meta-analysis and review of literature. BMC Rheumatol 2019; 3(1): 10.
[http://dx.doi.org/10.1186/s41927-019-0058-7] [PMID: 30886998]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy