Condition category
Musculoskeletal Diseases
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof J.M.W. Hazes


Contact details

Department of Rheumatology Ee965
3000 WB
+31 (0)10 703 4602

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Treatment in the Rotterdam Early Arthritis CoHort: a stratified, randomised clinical trial in patients with recent-onset arthritis



Study hypothesis

In each stratum of probability there is a clinically and statistically significant difference in the functional ability and disease activity score over time (area under the curve) and progression of radiological joint damage after one year of follow-up in recent-onset arthritic patients who were having induction treatment with divergent intensity.

Ethics approval

Medical Ethical Committee Erasmus University Rotterdam gave approval

Study design

Multicentre randomised single-centre parallel-group trial

Primary study design


Secondary study design

Randomised parallel trial

Trial setting


Trial type


Patient information sheet

Can be found at:


Recent onset arthritis, rheumatoid arthritis


Three monthly evaluations of disease activity score and safety. Medication adjustments by protocol, based on Disease Activity Score (DAS) calculations. If DAS is less than 2.4, medication will be switched to more intensive treatment including biologicals (initial biological will be etanersept). If DAS less than 1.6 is achieved for at least six months, patients will start to taper and finally stop all medication.

Induction therapy for the three strata will be:
1. High probability (HP)-group:
1.1. Methotrexate (MTX) + Sulfasalazine (SSZ) + Hydroxychloroquine (HCQ) + one single dose corticosteroid intramuscular
1.2. MTX + SSZ + HCQ + prednisone
1.3. MTX + prednisone
2. Intermediate Probability (IP)-group:
2.1. MTX
2.2. HCQ
2.3. Prednisone
3. Low Probability (LP)-group:
3.1. Naproxen
3.2. HCQ
3.3. One single dose corticosteroids intramuscular

Intervention type



Not Applicable

Drug names

Methotrexate, sulfasalazine, hydroxychloroquine, prednisone, naproxen

Primary outcome measure

1. Functional ability as measured by HAQ and DAS over time (area under the curve), assessed every 3 months
2. Progression of radiological joint damage as measured by Sharp/van der Heijde score, assessed every 6 months

Secondary outcome measures

1. American College of Rheumatology (ACR) arthritis core-set, assessed every 3 months
2. Quality of Life, as measured with 36-item Short Form (SF-36), European Quality of Life scale (EuroQoL), assessed every 3 months
3. Costs

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Participant of the REACH cohort (patients with inflammatory joint complaints less then one year)
2. All patients must at least have one (out of 66) swollen joint

Added 23/04/2009:
3. Aged 18 years or older, either sex

Participant type


Age group




Target number of participants


Total final enrolment


Participant exclusion criteria

1. Definite diagnosis of crystal arthropathy, (post) infective arthritis or autoimmune rheumatic disorder
2. Previous therapy with disease modifying anti-rheumatic drugs (DMARDs) or corticosteroids
3. Pregnancy or wish to become pregnant during the study, or childbearing potential without adequate contraception
4. Concomitant treatment with an other experimental drug
5. History or presence of malignancy within the last five years
6. Elevated hepatic enzyme levels (aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT] greater than two times normal value)
7. Thrombopoenia less than 150 x 10^9/l
8. Leucopoenia less than 3.0 x 10^9/l
9. Serum creatinine level greater than 150 umol/l

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Erasmus Medical Centre
3000 WB

Sponsor information


Erasmus Medical Centre (Netherlands)

Sponsor details

Department of Rheumatology
3000 CA

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Wyeth Pharmaceutical B.V. (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

1. 2009 protocol in:
2. 2012 results in:
3. 2014 1-year results in:
4. 2016 results in:
5. 2018 results in: (added 12/08/2019)
6. 2019 results on association between DNA methylation and methotrexate response in: (added 28/06/2019)

Publication citations

  1. Protocol

    Claessen SJ, Hazes JM, Huisman MA, van Zeben D, Luime JJ, Weel AE, Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial., BMC Musculoskelet Disord, 2009, 10, 71, doi: 10.1186/1471-2474-10-71.

  2. Results

    de Jong PH, Weel AE, de Man YA, Huisman AM, Gerards AH, van Krugten MV, Luime JJ, Hazes JM, Brief Report: to squeeze or not to squeeze, that is the question! Optimizing the disease activity score in 28 joints by adding the squeeze test of metatarsophalangeal joints in early rheumatoid arthritis., Arthritis Rheum., 2012, 64, 10, 3095-3101, doi: 10.1002/art.34568.

  3. de Jong PH, Hazes JM, Han HK, Huisman M, van Zeben D, van der Lubbe PA, Gerards AH, van Schaeybroeck B, de Sonnaville PB, van Krugten MV, Luime JJ, Weel AE, Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial., Ann. Rheum. Dis., 2014, 73, 7, 1331-1339, doi: 10.1136/annrheumdis-2013-204788.

  4. Results

    Kuijper TM, Luime JJ, de Jong PH, Gerards AH, van Zeben D, Tchetverikov I, de Sonnaville PB, van Krugten MV, Grillet BA, Hazes JM, Weel AE, Tapering conventional synthetic DMARDs in patients with early arthritis in sustained remission: 2-year follow-up of the tREACH trial, Ann Rheum Dis, 2016 , annrheumdis-2016-209272, doi: 10.1136/annrheumdis-2016-209272.

Additional files

Editorial Notes

12/08/2019: Publication reference and total final enrolment added. 28/06/2019: Publication reference added. 13/06/2016: Publication reference added. On 23/04/2009 this record was updated; all amendments can be found under the relevant field. At this time, the overall trial end date was updated - the initial overall trial end date at the time of registration was 15/11/2007.