TREAT Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid arthritis (TREAT EARLIER): a randomized, double-blind, placebo-controlled clinical trial protocol.
Clinically suspect arthralgia
Double-blind
Intervention
MRI
Methotrexate
Placebo-controlled
Prevention
Randomized
Rheumatoid arthritis
Subclinical inflammation
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
16 Oct 2020
16 Oct 2020
Historique:
received:
02
04
2020
accepted:
08
09
2020
entrez:
20
10
2020
pubmed:
21
10
2020
medline:
22
6
2021
Statut:
epublish
Résumé
We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical arthritis (clinically suspect arthralgia (CSA)) is effective in preventing progression from subclinical inflammation to clinically apparent persistent arthritis. Currently, rheumatoid arthritis (RA) can be recognized and diagnosed when arthritis (joint swelling) has become detectable at physical examination. Importantly, at this time, the immune processes have already matured, chronicity is established, and patients require long-standing treatment with disease-modifying anti-rheumatic drugs. The TREAT EARLIER trial studies the hypothesis that intervention in the symptomatic phase preceding clinical arthritis is more often successful in permanent disease modification because of less matured underlying disease processes. A two-level definition to identify patients that are prone to develop RA is used. First, patients should have CSA and recent-onset arthralgia (< 1 year) that is suspect to progress to RA according to the expertise of the treating rheumatologist. Second, patients need to have subclinical inflammation of the hand or foot joints at 1.5 T MRI. The trial aims to recruit 230 participants from secondary care hospital settings across the south-west region of The Netherlands. Intervention will be randomly assigned and includes a single-dose of intramuscular 120 mg methylprednisolon followed by methotrexate (increasing dose to 25 mg/week orally) or placebo (both; injection and tablets) over the course of 1 year. Thereafter, participants are followed for another year. The primary endpoint is the development of clinically detectable arthritis, either fulfilling the 2010 criteria for RA or unclassified clinical arthritis of ≥ 2 joints, which persists for at least 2 weeks. DMARD-free status is a co-primary endpoint. The patient-reported outcomes functioning, along with workability and symptoms, are key secondary endpoints. Participants, caregivers (including those assessing the endpoints), and scientific staff are all blinded to the group assignment. This proof-of-concept study is the logical consequence of pre-work on the identification of patients with CSA with MRI-detected subclinical joint inflammation. It will test the hypothesis whether intervention in patients in this early phase with the cornerstone treatment of classified RA (methotrexate) hampers the development of persistent RA and reduce the disease burden of RA. Dutch Trial Register NL4599 (NTR4853). Registered on 20 October 2014.
Sections du résumé
BACKGROUND
BACKGROUND
We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical arthritis (clinically suspect arthralgia (CSA)) is effective in preventing progression from subclinical inflammation to clinically apparent persistent arthritis. Currently, rheumatoid arthritis (RA) can be recognized and diagnosed when arthritis (joint swelling) has become detectable at physical examination. Importantly, at this time, the immune processes have already matured, chronicity is established, and patients require long-standing treatment with disease-modifying anti-rheumatic drugs. The TREAT EARLIER trial studies the hypothesis that intervention in the symptomatic phase preceding clinical arthritis is more often successful in permanent disease modification because of less matured underlying disease processes.
METHODS
METHODS
A two-level definition to identify patients that are prone to develop RA is used. First, patients should have CSA and recent-onset arthralgia (< 1 year) that is suspect to progress to RA according to the expertise of the treating rheumatologist. Second, patients need to have subclinical inflammation of the hand or foot joints at 1.5 T MRI. The trial aims to recruit 230 participants from secondary care hospital settings across the south-west region of The Netherlands. Intervention will be randomly assigned and includes a single-dose of intramuscular 120 mg methylprednisolon followed by methotrexate (increasing dose to 25 mg/week orally) or placebo (both; injection and tablets) over the course of 1 year. Thereafter, participants are followed for another year. The primary endpoint is the development of clinically detectable arthritis, either fulfilling the 2010 criteria for RA or unclassified clinical arthritis of ≥ 2 joints, which persists for at least 2 weeks. DMARD-free status is a co-primary endpoint. The patient-reported outcomes functioning, along with workability and symptoms, are key secondary endpoints. Participants, caregivers (including those assessing the endpoints), and scientific staff are all blinded to the group assignment.
DISCUSSION
CONCLUSIONS
This proof-of-concept study is the logical consequence of pre-work on the identification of patients with CSA with MRI-detected subclinical joint inflammation. It will test the hypothesis whether intervention in patients in this early phase with the cornerstone treatment of classified RA (methotrexate) hampers the development of persistent RA and reduce the disease burden of RA.
TRIAL REGISTRATION
BACKGROUND
Dutch Trial Register NL4599 (NTR4853). Registered on 20 October 2014.
Identifiants
pubmed: 33076964
doi: 10.1186/s13063-020-04731-2
pii: 10.1186/s13063-020-04731-2
pmc: PMC7574479
doi:
Substances chimiques
Antirheumatic Agents
0
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
862Subventions
Organisme : ZonMW
ID : 95104004
Références
Ann Rheum Dis. 2020 Mar;79(3):312-315
pubmed: 31915123
Clin Ther. 2019 Jul;41(7):1279-1285
pubmed: 31196657
Arthritis Res Ther. 2006;8(4):R133
pubmed: 16872514
JBR-BTR. 2014 Mar-Apr;97(2):126-7
pubmed: 25073253
Ann Rheum Dis. 2007 Sep;66(9):1216-20
pubmed: 17392347
Rheumatology (Oxford). 2014 Aug;53(8):1446-51
pubmed: 24659753
RMD Open. 2017 Nov 14;3(2):e000479
pubmed: 29177078
Best Pract Res Clin Rheumatol. 2017 Feb;31(1):3-18
pubmed: 29221595
Arthritis Res Ther. 2019 Nov 27;21(1):249
pubmed: 31771618
Ann Rheum Dis. 2017 Mar;76(3):491-496
pubmed: 27991858
RMD Open. 2017 Jun 29;3(1):e000419
pubmed: 28879045
Ann Rheum Dis. 2015 Apr;74(4):648-54
pubmed: 24323395
Rheumatology (Oxford). 2017 Oct 1;56(10):1700-1706
pubmed: 28957551
Ann Rheum Dis. 2017 May;76(5):855-861
pubmed: 27903508
Ann Rheum Dis. 2014 Aug;73(8):1549-51
pubmed: 24728329
Ann Rheum Dis. 2013 Jan;72(1):72-8
pubmed: 22679301
Ann Rheum Dis. 2010 Mar;69(3):503-9
pubmed: 19825849
J Magn Reson Imaging. 2015 May;41(5):1291-9
pubmed: 24912802
Ann Rheum Dis. 2017 Dec;76(12):2054-2060
pubmed: 28866645
Ann Rheum Dis. 2014 May;73(5):845-53
pubmed: 23520035
Ann Rheum Dis. 2011 Feb;70(2):259-65
pubmed: 21156761
Ann Rheum Dis. 2017 Oct;76(10):1751-1754
pubmed: 28606964
BMC Musculoskelet Disord. 2011 Jun 06;12:128
pubmed: 21645348
Ann Rheum Dis. 2007 Nov;66(11):1409-10
pubmed: 17934080
Ann Rheum Dis. 2017 Jun;76(6):948-959
pubmed: 27979873
RMD Open. 2019 Apr 3;5(1):e000870
pubmed: 31168406
Ann Rheum Dis. 2010 Mar;69(3):495-502
pubmed: 20223838
J Rheumatol. 2019 Sep;46(9):1222-1227
pubmed: 30770509
RMD Open. 2018 Jun 20;4(1):e000728
pubmed: 29955387
Ann Rheum Dis. 2015 Jun;74(6):1225-32
pubmed: 24718962
RMD Open. 2015 Mar 04;1(1):e000041
pubmed: 26509063
Arthritis Res Ther. 2005;7(5):R949-58
pubmed: 16207336
RMD Open. 2015 Feb 18;1(1):e000005
pubmed: 26509042
Arthritis Care Res (Hoboken). 2018 Apr;70(4):510-515
pubmed: 28622462
Arthritis Rheum. 2003 Oct;48(10):2741-9
pubmed: 14558078
Ann Rheum Dis. 2012 May;71(5):638-41
pubmed: 22387728
Ann Rheum Dis. 2014 Feb;73(2):396-400
pubmed: 23334213
Rheumatology (Oxford). 2006 Nov;45(11):1389-94
pubmed: 16606655
Ann Rheum Dis. 2013 Aug;72(8):1295-301
pubmed: 22952388
Nat Rev Rheumatol. 2016 Dec;12(12):731-742
pubmed: 27784891
Rheumatology (Oxford). 2016 Jun;55(6):1140-1
pubmed: 26742783
Arthritis Rheum. 2004 Feb;50(2):380-6
pubmed: 14872479
Scand J Work Environ Health. 1979;5 suppl 3:19-24
pubmed: 397615
Ann Rheum Dis. 2014 Mar;73(3):510-5
pubmed: 24395555
Ann Rheum Dis. 2005 Feb;64 Suppl 1:i3-7
pubmed: 15647420
Ann Rheum Dis. 2016 Oct;75(10):1824-30
pubmed: 26613769
Ann Rheum Dis. 2020 Apr;79(4):460-463
pubmed: 32033935
Nat Rev Rheumatol. 2018 Jan;14(1):32-41
pubmed: 29118439
Arthritis Care Res (Hoboken). 2018 Jul;70(7):987-996
pubmed: 29266813
Rheumatology (Oxford). 2017 Dec 1;56(12):2123-2128
pubmed: 28968699
Ann Rheum Dis. 2020 Jun;79(6):685-699
pubmed: 31969328
Ann Rheum Dis. 2014 Mar;73(3):492-509
pubmed: 24161836
Arthritis Rheum. 2010 Sep;62(9):2569-81
pubmed: 20872595