Advertisement

Drugs

, Volume 78, Issue 16, pp 1705–1715 | Cite as

Tapering and Discontinuation of Biologics in Patients with Psoriatic Arthritis with Low Disease Activity

  • Weiyu Ye
  • Laura J. Tucker
  • Laura C. Coates
Review Article
  • 61 Downloads

Abstract

The introduction of biologic disease modifying anti-rheumatic drugs (bMDARDs) have revolutionised the treatment of psoriatic arthritis (PsA). This combined with a ‘treat-to-target’ approach, means that achieving remission is increasingly possible. In patients with well-controlled PsA, there is little consensus on whether bDMARDs should be continued, tapered or discontinued altogether. Tapering or discontinuation of bDMARDs could offer significant financial savings and minimise patient burden and unwanted drug-related side effects. However, there is a risk of loss of remission. The primary focus of this paper is to review the current evidence on bDMARD tapering and discontinuation in PsA. We explore the criteria employed by studies to define patients eligible for bDMARD tapering or discontinuation and the process by which this occurs. We also review the outcomes of bDMARD tapering and discontinuation, the predictors, and the likelihood of restoring remission following relapse. To date, bDMARD tapering seems to be feasible and safe in patients with PsA who are in remission or with low disease activity. Lower disease activity prior to tapering seems to increase the likelihood of successful bDMARD tapering. In contrast, discontinuing bDMARDs appears to carry a substantial risk of loss of remission. Those with higher disease activity at time of tumour necrosis factor inhibitors discontinuation, current smokers, male sex, increased skin involvement, and synovial hypertrophy seen on ultrasound prior to discontinuation are at greater risk of losing remission post-bDMARD discontinuation. In those who lose remission, reinstating the standard dose of bDMARD appears to be effective in restoring remission.

Notes

Compliance with Ethical Standards

Funding

Weiyu Ye is an academic foundation trainee. Laura J Tucker is funded by the Norman Collisson Foundation as a Clinical Research Fellow. Laura C Coates is funded by a National Institute for Health Research Clinician Scientist award. The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Conflict of interest

Laura C Coates has received research funding and/or honoraria from Abbvie, Amgen, BMS, Celgene, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Prothena and UCB. Weiyu Ye and Laura J Tucker have no conflicts of interest to disclose.

References

  1. 1.
    Van den Bosch F, Coates L. Clinical management of psoriatic arthritis. Lancet. 2018;391(10136):2285–94.CrossRefGoogle Scholar
  2. 2.
    Gudu T, Kiltz U, de Wit M, Kvien TK, Gossec L. Mapping the effect of psoriatic arthritis using the international classification of functioning, disability and health. J Rheumatol. 2017;44:193.CrossRefGoogle Scholar
  3. 3.
    Gossec L, Smolen JS, Ramiro S, de Wit M, Cutolo M, Dougados M, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016;75(3):499–510.CrossRefGoogle Scholar
  4. 4.
    NICE [TA199]. Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis. 2010. https://www.nice.org.uk/guidance/ta199. Accessed 25 September 2018.
  5. 5.
    Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50(7):2264–72.CrossRefGoogle Scholar
  6. 6.
    Coates LC, Moverley AR, McParland L, Brown S, Navarro-Coy N, O’Dwyer JL, et al. Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial. Lancet. 2015;386(10012):2489–98.CrossRefGoogle Scholar
  7. 7.
    Herwaarden N, Broeder AA, Jacobs W, Maas A, Bijlsma JWJ, Vollenhoven RF, Bemt BJF. Down-titration and discontinuation strategies of tumor necrosis factor–blocking agents for rheumatoid arthritis in patients with low disease activity. Cochrane Database Syst Rev. 2014.  https://doi.org/10.1002/14651858.cd010455.pub2.CrossRefPubMedGoogle Scholar
  8. 8.
    Henaux S, Ruyssen-Witrand A, Cantagrel A, Barnetche T, Fautrel B, Filippi N, et al. Risk of losing remission, low disease activity or radiographic progression in case of bDMARD discontinuation or tapering in rheumatoid arthritis: systematic analysis of the literature and meta-analysis. Ann Rheum Dis. 2018;77(4):515–22.CrossRefGoogle Scholar
  9. 9.
    Brandt J, Khariouzov A, Listing J, Haibel H, Sörensen H, Grassnickel L, et al. Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum. 2003;48(6):1667–75.CrossRefGoogle Scholar
  10. 10.
    Cantini F, Niccoli L, Cassarà E, Kaloudi O, Nannini C. Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study. Biologics. 2013;7:1–6.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis. 2010;69(01):48–53.CrossRefGoogle Scholar
  12. 12.
    Lorenzin M, Ortolan A, de Hooge M, Frallonardo P, Piccoli A, Cozzi F, et al. Lengthening the time intervals between doses of biological agents in psoriatic arthritis patients: a single-center retrospective study. Int J Immunopathol Pharmacol. 2015;28(4):479–87.CrossRefGoogle Scholar
  13. 13.
    Janta I, Martínez-Estupiñán L, Valor L, Montoro M, Rodriguez OB, Aragüés IH, et al. Comparison between full and tapered dosages of biologic therapies in psoriatic arthritis patients: clinical and ultrasound assessment. Clin Rheumatol. 2015;34(5):935–42.CrossRefGoogle Scholar
  14. 14.
    Fong W, Holroyd C, Davidson B, Armstrong R, Harvey N, Dennison E, et al. The effectiveness of a real life dose reduction strategy for tumour necrosis factor inhibitors in ankylosing spondylitis and psoriatic arthritis. Rheumatology (Oxford). 2016;55(10):1837–42.CrossRefGoogle Scholar
  15. 15.
    Lόpez-Vives PV, Estrada I, Martín-Esteve M, Aparicio X, Juanola JM, Nolla J Rodríguez-Moreno. Dose reduction and/or withdrawal of anti-TN treatment in psoriatic arthritis. Annal Rheum Dis. 2012;71(3):108–9.Google Scholar
  16. 16.
    Cantini F, Niccoli L, Cassarà E, Kaloudi O, Nannini C. Sustained maintenance of clinical remission after adalimumab dose reduction in patients with early psoriatic arthritis: a long-term follow-up study. Biologics. 2012;6:201–6.PubMedPubMedCentralGoogle Scholar
  17. 17.
    de Stefano R, Frati E, de Quattro D, de Stefano L. Low doses of etanercept can be effective to maintain remission in psoriatic arthritis patients. J Clin Rheumatol. 2018;24(3):127–31.PubMedGoogle Scholar
  18. 18.
    J B, Anton R, Navarro Ruiz A, Castera M, Jd R, A M. Persistence and econ”mic impact of etanercept and adalimumab dose reduction in rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis patients with at least 1 year in clinical remission: experience from 2 Spanish teaching hospitals during 5 years of follow-up. Value Health. 2015;18:A643 [abstract].CrossRefGoogle Scholar
  19. 19.
    Chimenti MS, Esposito M, Giunta A, Graceffa D, Babino G, Teoli M, et al. Remission of psoriatic arthritis after etanercept discontinuation: analysis of patients’ clinical characteristics leading to disease relapse. Int J Immunopathol Pharmacol. 2013;26(3):833–8.CrossRefGoogle Scholar
  20. 20.
    Huynh DH, Boyd TA, Etzel CJ, Cox V, Kremer J, Mease P, et al. Persistence of low disease activity after tumour necrosis factor inhibitor (TNFi) discontinuation in patients with psoriatic arthritis. RMD Open. 2017;3(1):e000395.CrossRefGoogle Scholar
  21. 21.
    Moverley A, Coates L, Marzo-Ortega H, Waxman R, Torgerson D, Cocks K, et al. A feasibility study for a randomised controlled trial of treatment withdrawal in psoriatic arthritis (REmoval of treatment for patients in REmission in psoriatic ArThritis (RETREAT (F)). Clin Rheumatol. 2015;34(8):1407–12.CrossRefGoogle Scholar
  22. 22.
    Cantini F, Niccoli L, Nannini C, Cassarà E, Pasquetti P, Olivieri I, et al. Frequency and duration of clinical remission in patients with peripheral psoriatic arthritis requiring second-line drugs. Rheumatology (Oxford). 2008;47(6):872–6.CrossRefGoogle Scholar
  23. 23.
    Araujo EG, Finzel S, Englbrecht M, Schreiber DA, Faustini F, Hueber A, et al. High incidence of disease recurrence after discontinuation of disease-modifying antirheumatic drug treatment in patients with psoriatic arthritis in remission. Ann Rheum Dis. 2015;74(4):655–60.CrossRefGoogle Scholar
  24. 24.
    Merola JF, Lockshin B, Mody EA. Switching biologics in the treatment of psoriatic arthritis. Semin Arthritis Rheum. 2017;47:29–37.CrossRefGoogle Scholar
  25. 25.
    Costa L, Perricone C, Chimenti MS, et al. Switching between biological treatments in psoriatic arthritis: a review of the evidence. Drugs R D. 2017;17:509–22.CrossRefGoogle Scholar
  26. 26.
    González-Álvaro I, Martínez-Fernández C, Dorantes-Calderón B, García-Vicuña R, Hernández-Cruz B, Herrero-Ambrosio A, et al. Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Rheumatology (Oxford). 2015;54(7):1200–9.CrossRefGoogle Scholar
  27. 27.
    González-Álvaro I, Blasco AJ, Lázaro P, Sánchez-Piedra C, Almodovar R, Bachiller-Corral J, et al. REDOSER project: optimising biological therapy dose for rheumatoid arthritis and spondyloarthritis patients. Heliyon. 2017;3(11):e00452.CrossRefGoogle Scholar
  28. 28.
    ReDOSER calculator. http://redoser.ser.es/#!/. Accessed 1 Oct 2018.

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Room 3A31, The Cairns Library IT Corridor, Level 3, John Radcliffe Hospital (Main Hospital)Oxford University Clinical Academic Graduate School, University of OxfordOxfordUK
  2. 2.Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal SciencesUniversity of OxfordOxfordUK

Personalised recommendations