TNF-blocking Therapy in Combination With Disease-modifying Antirheumatic Drugs in Early Rheumatoid Arthritis

NCT00908089 | Unknown Phase 4 DMC

• 1 other identifier: NEO-RACo
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 13

Brief Summary

The FIN-RACo trial is an investigator initiated multicenter (n=15 centers in Finland) prospective study on the treatment of patients with early rheumatoid arthritis (RA) with combination therapy with disease modifying antirheumatic drugs starting with methotrexate, sulphasalazine, hydroxychloroquine and prednisolone (COMBI). During the first 6 months, the patients are randomized to treatment with infliximab/placebo added on the combination treatment. The study is prospective for 5 years, with extension to 10 years. The target is to induce remission in both treatment arms. To reach this target, the investigators use frequent changes of doses and anti-rheumatic drugs and use of intra-articular glucocorticoid injections. The primary endpoints are the proportions of patients with remission at 2 and 5 years in both treatment arms.

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis; methotrexate; sulfasalazine; hydroxychloroquine; infliximab

Outcome Measures

Primary Outcomes (1)

• Remission by ACR criteria

  2 years

Secondary Outcomes (3)

• Radiology (erosions)

  2 years

• Sustained remission

  2 years

• Costs

  2

Other Outcomes (13)

• HAQ

  1, 2, 3, 4 and 5 years

• Work disability

  2, 3, 4 and 5 years

• Good response

  5 years

Study Arms (2)

Trexan+Salazopyrin+Oxiklorin+prednisolone + infliximab

ACTIVE COMPARATOR

Combination therapy with 3 DMARDs (starting with methotrexate 10-25 mg/week, sulphasalazine 1-2 g/day and hydroxychloroquine 35 mg/kg/week)+ Prednisolon 7.5 mg/day + infliximab 3 mg/kg at weeks 4, 6, 10, 18, 26

Drug: Trexan+Salazopyrin+Oxiklorin+prednisolone + infliximab

Trexan+Salazopyrin+Oxiklorin+prednisolone + placebo

PLACEBO COMPARATOR

Combination therapy with 3 DMARDs (starting with methotrexate 10-25 mg/week, sulphasalazine 1-2 g/day and hydroxychloroquine 25 mg/kg/week)+ Prednisolon 7.5 mg/day + placebo at weeks 4, 6, 10, 18, 26

Drug: Trexan+Salazopyrin+Oxiklorin+prednisolone + placebo

Interventions

Trexan+Salazopyrin+Oxiklorin+prednisolone + infliximab DRUG

methotrexate 10-25 mg/week, sulfasalazine 1-2 g/day, hydroxychloroquine 35 mg/kg/week, prednisolone 7.5 mg/day, and infliximab 3 mg/kg during first 6 months

Also known as: Trexan, Salazopyrin, Oxiklorin, Prednison, Remicade

Trexan+Salazopyrin+Oxiklorin+prednisolone + infliximab

Trexan+Salazopyrin+Oxiklorin+prednisolone + placebo DRUG

methotrexate 10-25 mg/week, sulfasalazine 1-2 g/day, hydroxychloroquine 35 mg/kg/week, prednisolone 7.5 mg/day, and placebo infusion during first 6 months

Also known as: Trexan, Salazopyrin, Oxiklorin, Prednison, 0.9% NaCl

Trexan+Salazopyrin+Oxiklorin+prednisolone + placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of RA fulfilling the ACR classification criteria for RA
• Patients within age group of 18-60 years
• Patients not permanently work disabled or retired
• Duration of symptoms \< 12 months, and who have not received DMARD previously
• Patients with active disease (see below)
• Criteria for active disease at entry:
• \> 6 swollen joints (66 joint count)
• \> 6 tender joints (68 joint count)
• duration of early morning stiffness \> 45 min and/or ESR \> 30 mm/h and/or CRP \> 20 mg/l

You may not qualify if:

• Previous treatment with DMARDs
• Previous treatment with oral glucocorticoids during the previous 6 months
• Less than 30 days from previous intra-articular injection with corticosteroids
• Allergy to sulphonamides
• Allergy to acetylsalicylic acid
• Allergy to methotrexate
• Allergy to antimalarials
• Previous treatment with biologicals
• Serum creatinine value \> upper limit of normal (registered in 2 different blood samples)
• Serum transaminase levels \> 2x upper limit of normal (registered in 2 different samples)
• Known/previous malignancy excluding basalioma or in situ cervical cancer \>5 years previously
• Cardiac failure (NYHA III-IV)
• Previous history of tuberculosis and/or exposition to tuberculosis and/or typical changes of previous/active tuberculosis in chest radiology
• Active infection
• Pregnancy

Sponsors & Collaborators

• University of Helsinki: lead
• Seinajoki Central Hospital: collaborator
• Oulu University Hospital: collaborator
• Jyväskylä Central Hospital: collaborator
• Kuopio University Hospital: collaborator
• Satakunta Central Hospital: collaborator
• University of Turku: collaborator
• Rheumatism Foundation Hospital: collaborator
• Orton Invalid Foundation: collaborator
• South Carelia Central Hospital: collaborator
• Lappi Central Hospital: collaborator
• Kanta-Häme Central Hospital: collaborator

Study Sites (13)

Hämeenlinna Central Hospital

Hämeenlinna, FI-13530, Finland

Location

Rheumatism Foundation Hospital

Heinola, FI-18120, Finland

Location

Helsinki University Central Hospital

Helsinki, FI-00029 HUS, Finland

Location

Orton Invalid Foundation Hospital

Helsinki, FI-00280, Finland

Location

Jyväskylä Central Hospital

Jyväskylä, FI-40620, Finland

Location

Kuopio University Hospital

Kuopio, FI-703211, Finland

Location

Lappeenranta Central Hospital

Lappeenranta, FI-53130, Finland

Location

Oulu University Hospital

Oulu, FI-90029 OYS, Finland

Location

Satakunta Central Hospital

Rauma, FI-26100, Finland

Location

Rovaniemi Central Hospital

Rovaniemi, FI-96100, Finland

Location

Seinäjoki Central Hospital

Seinäjoki, FI-60220, Finland

Location

Tampere University Hospital

Tampere, FI-33521, Finland

Location

Turku University Central Hospital

Turku, FI-21540, Finland

Location

Related Publications (7)

• Leirisalo-Repo M, Kautiainen H, Laasonen L, Korpela M, Kauppi MJ, Kaipiainen-Seppanen O, Luosujarvi R, Luukkainen R, Karjalainen A, Blafield H, Uutela T, Ilva K, Julkunen HA, Paimela L, Puolakka K, Moilanen E, Hannonen PJ, Mottonen T; NEO-RACo Study Group. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann Rheum Dis. 2013 Jun;72(6):851-7. doi: 10.1136/annrheumdis-2012-201365. Epub 2012 Jun 30.

  PMID: 22753402 RESULT

• Rantalaiho V, Kautiainen H, Jarvenpaa S, Korpela M, Malmi T, Hannonen P, Kaipiainen-Seppanen O, Yli-Kerttula T, Mottonen T, Mustila A, Karjalainen A, Paimela L, Uutela T, Leirisalo-Repo M; NEO-RACo Study Group. Failure in longterm treatment is rare in actively treated patients with rheumatoid arthritis, but may be predicted by high health assessment score at baseline and by residual disease activity at 3 and 6 months: the 5-year followup results of the randomized clinical NEO-RACo trial. J Rheumatol. 2014 Dec;41(12):2379-85. doi: 10.3899/jrheum.140267. Epub 2014 Oct 1.

  PMID: 25274892 RESULT

• Rantalaiho V, Kautiainen H, Korpela M, Hannonen P, Kaipiainen-Seppanen O, Mottonen T, Kauppi M, Karjalainen A, Laiho K, Laasonen L, Hakola M, Peltomaa R, Leirisalo-Repo M; NEO-RACo Study Group. Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab. The 5-year follow-up results of a randomised clinical trial, the NEO-RACo trial. Ann Rheum Dis. 2014 Nov;73(11):1954-61. doi: 10.1136/annrheumdis-2013-203497. Epub 2013 Aug 1.

  PMID: 23908187 RESULT

• Sandstrom T, Kaipiainen-Seppanen O, Mali M, Kauppi M, Kautiainen H, Hannonen P, Yli-Kerttula T, Leirisalo-Repo M, Rantalaiho V. Limited reduction of bone mineral density in patients with early rheumatoid arthritis receiving aggressive treatment: 10 year results of the NEO-RACo study. Scand J Rheumatol. 2025 Nov;54(6):412-420. doi: 10.1080/03009742.2025.2515696. Epub 2025 Jun 23.

  PMID: 40548492 DERIVED

• Vuolteenaho K, Tuure L, Nieminen R, Laasonen L, Leirisalo-Repo M, Moilanen E; NEO-RACo Study Group. Pretreatment resistin levels are associated with erosive disease in early rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs and infliximab. Scand J Rheumatol. 2022 May;51(3):180-185. doi: 10.1080/03009742.2021.1929456. Epub 2021 Jul 15.

  PMID: 34263700 DERIVED

• Sandstrom T, Rantalaiho V, Yli-Kerttula T, Kautiainen H, Malmi T, Karjalainen A, Uusitalo T, Julkunen H, Kaipiainen-Seppanen O, Paimela L, Puolakka K, Uutela T, Mottonen T, Hannonen P, Leirisalo-Repo M, Laasonen L, Kauppi M; NEO-RACo Study Group. Cervical Spine Involvement among Patients with Rheumatoid Arthritis Treated Actively with Treat-to-target Strategy: 10-year Results of the NEO-RACo Study. J Rheumatol. 2020 Aug 1;47(8):1160-1164. doi: 10.3899/jrheum.190139. Epub 2019 Nov 15.

  PMID: 31732558 DERIVED

• Rantalaiho V, Sandstrom T, Koski J, Hannonen P, Mottonen T, Kaipiainen-Seppanen O, Yli-Kerttula T, Kauppi MJ, Uutela T, Malmi T, Julkunen H, Laasonen L, Kautiainen H, Leirisalo-Repo M; NEO-RACo Study Group. Early Targeted Combination Treatment With Conventional Synthetic Disease-Modifying Antirheumatic Drugs and Long-Term Outcomes in Rheumatoid Arthritis: Ten-Year Follow-Up Results of a Randomized Clinical Trial. Arthritis Care Res (Hoboken). 2019 Nov;71(11):1450-1458. doi: 10.1002/acr.23782.

  PMID: 30295425 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Infliximab; Naltrexone; Sulfasalazine; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring

Study Officials

• Marjatta Leirisalo-Repo, MD, Prof

  University of Helsinki

  STUDY DIRECTOR

• Timo Möttönen, MD, Prof

  University of Turku

  STUDY CHAIR

• Markku Korpela, MD, PhD

  Tampere University

  STUDY CHAIR

• Riitta Luosujärvi, MD, PhD

  Helsinki University Central Hospital

  STUDY CHAIR

• Oili Kaipiainen-Seppänen, MD, PhD

  Kuopio University Hospital

  STUDY CHAIR

• Markku Kauppi, MD, PhD

  Päijänne Tavastia Central Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Prof

Study Record Dates

• First Submitted: May 22, 2009
• First Posted: May 25, 2009
• Study Start: March 1, 2003
• Primary Completion: May 1, 2007
• Study Completion: December 1, 2015
• Last Updated: April 1, 2015

Record last verified: 2015-03

Locations

FI (13)