Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Jan 14;2(1):e000133.
doi: 10.1136/rmdopen-2015-000133. eCollection 2016.

A multicentre, randomised, controlled, open-label pilot study on the feasibility of discontinuation of adalimumab in established patients with rheumatoid arthritis in stable clinical remission

Katerina Chatzidionysiou  1 , Carl Turesson  2 , Annika Teleman  3 , Ann Knight  4 , Elisabet Lindqvist  5 , Per Larsson  6 , Lars Cöster  7 , Kristina Forslind  8 , Ronald van Vollenhoven  1 , Mikael Heimbürger  9
Affiliations

A multicentre, randomised, controlled, open-label pilot study on the feasibility of discontinuation of adalimumab in established patients with rheumatoid arthritis in stable clinical remission

Katerina Chatzidionysiou et al. RMD Open. .

Abstract

Objectives: Treatment with tumour necrosis factor (TNF) blockers, once started as therapy for rheumatoid arthritis (RA), is usually continued indefinitely. The aim of this trial was to assess the possibility of discontinuing treatment with adalimumab (ADA) while maintaining remission in patients with RA with established disease in stable remission on combination therapy with ADA and methotrexate (MTX).

Methods: In a randomised, controlled, open-label pilot study of patients with RA in stable remission treated with ADA+MTX, patients were randomised in a 1:1 ratio to continue with ADA plus MTX (arm AM) or MTX monotherapy (arm M) for 52 weeks. Flare was defined as Disease Activity Score (DAS28) ≥2.6 or a change in DAS28 (ΔDAS28) of >1.2 from baseline at any time. Patients in arm M with a flare restarted ADA. The primary end point was the proportion of patients in remission at week 28.

Results: 31 patients were enrolled in the study and randomised to arm AM (n=16) or arm M (n=15). At 28 weeks, 15/16 patients (94%) and 5/15 patients (33%) in arms AM and M, respectively, were in remission (p=0.001). During the first 28 weeks, 50% (8/16) in the AM arm and 80% (12/15) in the M arm had a flare (p=0.08). The number of patients in the AM and M arms with ≥1 ΔDAS28 >1.2 during the first 28 weeks was 1/16 (6%) and 8/15 (53%), respectively (p=0.005).

Conclusions: In this study, remission was rarely maintained in patients with long-standing disease who discontinued ADA. Discontinuation may be feasible in only a minority of patients with established RA in stable clinical remission.

Trial registration number: NCT00808509.

Keywords: Anti-TNF; Rheumatoid Arthritis; Treatment.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Study design. *Flare, DAS28 ≥2.6 or a change in DAS28 (ΔDAS28) >1.2 from baseline at any time. ADA, adalimumab; eow, every other week; MTX, methotrexate.
Figure 2
Figure 2
Disposition of patients through the study. *One patient was later excluded from each arm, one in the M arm due to a major protocol violation at week 8 and one in the AM arm who did not fulfil the inclusion criteria. Arm AM: patients treated with adalimumab and methotrexate; Arm M: patients treated with methotrexate only.
Figure 3
Figure 3
Primary (A) and secondary (B–G) end points. Arm AM: patients treated with adalimumab and methotrexate; Arm M: patients treated with methotrexate only.
Figure 4
Figure 4
Flare-free survival. Arm AM: patients treated with adalimumab and methotrexate; Arm M: patients treated with methotrexate only.
See this image and copyright information in PMC

References

    1. Tracey D, Klareskog L, Sasso EH et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008;117:244–79. 10.1016/j.pharmthera.2007.10.001 - DOI - PubMed
    1. Breedveld FC, Weisman MH, Kavanaugh AF et al. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006;54:26–37. 10.1002/art.21519 - DOI - PubMed
    1. Weinblatt ME, Keystone EC, Furst DE et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003;48:35–45. 10.1002/art.10697 - DOI - PubMed
    1. Lipsky PE, van der Heijde DM, St Clair EW et al. , Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 2000;343:1594–602. 10.1056/NEJM200011303432202 - DOI - PubMed
    1. Quinn MA, Conaghan PG, O'Connor PJ et al. Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2005;52:27–35. 10.1002/art.20712 - DOI - PubMed

Associated data