Rheumatoid ArthritisPhase 4NCT01491815
Active Conventional Therapy Compared to Three Different Biologic Treatments in Early Rheumatoid Arthritis With Subsequent Dose Reduction
A Phase 4 study testing Non-biological DMARD's, Cimzia and Orencia in people with Rheumatoid Arthritis, run by Karolinska Institutet at 30 sites in 6 countries.
Trial summary
This is an international (Sweden, Finland, Norway, Denmark, Iceland and the Netherlands) trial designed to compare the safety and efficacy of active conventional therapy (ACT) and three biologic treatments in subjects with early rheumatoid arthritis (RA). The global aim of this study is to assess and compare 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Non-biological DMARD's, Cimzia and Orencia
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 812 participants
- Where
- 30 sitesin 6 countries
- Study dates
- 14 Dec 2012to Dec 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is ≥18 years of age.
- Subject has a diagnosis of RA as defined by the newly established ACR/EULAR criteria, 2010. (Patients should also be classified according to the 1987-revised ACR-classification criteria, without this being an inclusion criteria).
- <24 months from arthritis symptom debut (symptom duration will be registered).
- Subject must have DAS28 (CRP) > 3.2.
- ≥ 2 swollen joints AND ≥ 2 tender joints.
- Subject must fulfill one of the following three criteria: RF positive OR ACPA positive OR CRP >10 mg/L.
Show all 14Show fewer
- Female subject is either not of childbearing potential (postmenopausal, surgically sterile etc.), or is of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion:
- Intrauterine device (IUD)
- Contraceptives (oral, parenteral, patch) for three months prior to study drug administration)
- A vasectomized partner
- Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening visit.
- Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (CXR), and 12-lead electrocardiogram (ECG) performed at Screening.
- Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
- Subjects must be able and willing to self-administer s.c. injections or have a qualified person available to administer s.c. injections.
Who cannot join
- Subject has been previously treated with disease modifying antirheumatic drugs (DMARDs) for rheumatic diseases.
- Current active inflammatory joint disease other than RA.
- Subjects has had a dose of prednisone (or equivalent) >7.5 mg/day or has had a dose change within the preceding 4 weeks.
- Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks. Inhaled corticosteroids for stable medical conditions are allowed.
- Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study).
- Subject has chronic arthritis diagnosed before age 17 years.
Show all 33Show fewer
- Subject has a history of an allergic reaction or significant sensitivity to constituents of study drugs.
- Subject has been treated with any investigational drug within one month prior to screening visit.
- Active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization within 4 weeks of screening.
- Subject has a poorly controlled medical condition, such as uncontrolled diabetes, unstable heart disease, congestive heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the study.
- Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal or liver disease (e.g., fibrosis, cirrhosis, hepatitis).
- Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease.
- Subject has history of cancer or lymphoproliferative disease. Allowable exceptions:
- Successfully treated cutaneous squamous cell or basal cell carcinoma
- Localized carcinoma in situ of the cervix
- Curatively treated malignancy (treatment terminated) > 5 years prior to screening
- Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (iv) anti-infectives within 30 days or oral anti-infectives within 14 days prior to the BL visit.
- Subjects will be evaluated for latent TB infection with a PPD or QuantiFERON test and X-ray. Subjects with evidence for latent TB will not be enrolled but first assessed according to local guidelines.
- Subject is known to have immune deficiency, history of Human Immunodeficiency Virus (HIV) or is otherwise severely immunocompromised.
- Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or within 150 days after the last dose of study medication.
- Men who are planning to father a child during the time they are included in the study
- Subject has a history of clinically significant drug or alcohol usage in the last year.
- Subject has a chronic widespread pain syndrome.
- Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
- Subject is unwilling to comply with the study protocol.
- Screening clinical laboratory analyses show any of the following abnormal laboratory results:
- Aspartate transaminase (AST) or alanine transaminase (ALT) > 1.75 times upper limit of normal (ULN).
- Positive serum human chorionic gonadotropin (hCG).
- Positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C serology indicative of current infection.
- Creatinine levels > 2x the ULN. If creatinine 1-2 times ULN, check GFR.
- Hemoglobin < 90 g/L.
- Absolute neutrophil count (ANC) < 1.5 x 10^3/microL.
- Serum total bilirubin > 1.5 mg/dL (>26 micromol/L).
Trial locations and contacts
30 sites in 6 countries.
30 sites in 6 countries
Sweden12 sites
Falu Hospital
Falun
Sahlgrenska University Hospital
Gothenburg
The Karolinska University Hospital
Huddinge
Linköping University Hospital
Linköping
Skåne University Hospital
Lund
Skåne University Hospital
Malmö
Örebro University Hospital
Örebro
The Karolinska University Hospital
Solna
Academic Specialist Center
Stockholm
The Karolinska Institutet
Stockholm
Uppsala University Hospital
Uppsala
Västmanlands Hospital
Västerås
Denmark7 sites
Aalborg University Hospital
Aalborg
Aarhus University Hospital
Aarhus
Rigshospitalet
Copenhagen
Odense University Hospital
Odense
Silkeborg University Clinic
Silkeborg
University Hospital of Southern Denmark
Sønderborg
Svendborg Hospital OUH
Svendborg
Norway5 sites
Ålesund Hospital
Ålesund
Haukeland University Hospital
Bergen
Diakonhjemmet Hospital
Oslo
University Hospital of North Norway
Tromsø
St. Olav's Hospital
Trondheim
Finland4 sites
Helsinki University Central Hospital
Helsinki
Central Finland Central Hospital
Jyväskylä
Kuopio University Hospital
Kuopio
Tampere University Hospital
Tampere
About this study
Official title: A Multicenter, Randomized, Open-label, Blinded-assessor, Phase 4 Study in Patients With Early Rheumatoid Arthritis to Compare Active Conventional Therapy Versus Three Biologic Treatments, and Two De-escalation Strategies in Patients Who Respond to Treatment
This is an international (Sweden, Finland, Norway, Denmark, Iceland and the Netherlands) trial designed to compare the safety and efficacy of active conventional therapy (ACT) and three biologic treatments in subjects with early rheumatoid arthritis (RA). The global aim of this study is to assess and compare
- the proportion of subjects who achieve remission with ACT versus three different biologic therapies (Certolizumab-pegol, Abatacept or Tocilizumab)
- two alternative de-escalation strategies in patients who respond to first-line therapy.
Read the detailed description
After completed enrollment a total of 812 patients were included in the study.
371 of the included patients have entered treatment part 2, 256 patients have exited the study after treatment part 1, 207 patients have had early termination and 322 patients have completed the full study.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Non-biological DMARD's, Cimzia, Orencia, RoActemra
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-biological DMARD'sDrug
Methotrexate: 25mg/week. SSZ: 2 g/day. HCQ: 35 mg/kg/week (Finland and Denmark) Methotrexate: 25mg/week. Prednisolone 20 mg/day tapered in 9 weeks to 5 mg/day, discontinued after 9 months. (Sweden, Norway, Iceland, and the Netherlands)
CimziaBiological
Certolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week
OrenciaBiological
Abatacept: 125 mg s.c. every week. Methotrexate: 25mg/week
RoActemraBiological
Tocilizumab is given as 4-weekly infusions at dosage 8 mg/kg or 162 mg in solution s.c. every week.
Methotrexate: 25mg/week
| Study group | Role | What they receive |
|---|---|---|
| Active conventional therapy (ACT) | Active comparator | Non-biological DMARD's: Methotrexate plus steroids or Methotrexate plus Sulphasalazine and Hydroxychloroquine and steroids Receives: Drug: Non-biological DMARD's |
| Biologic agent 1 | Active comparator | Cimzia: Certolizumab-pegol plus Methotrexate and steroids Receives: Biological: Cimzia |
| Biologic agent 2 | Active comparator | Orencia: Abatacept plus Methotrexate and steroids Receives: Biological: Orencia |
| Biologic agent 3 | Active comparator | RoActemra: Tocilizumab plus Methotrexate and steroids Receives: Biological: RoActemra |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients in remission at week 24 from baseline according to CDAI
Treatment Part 1: The primary efficacy outcome is the proportion of patients in remission at week 24 from BL according to CDAI
Measured: 24 weeks from BL
The proportion of patients in remission at week 24 after dose-reduction according to CDAI
Treatment Part 2: The primary efficacy outcome is the proportion of patients in remission according to CDAI, at the time point 24 weeks after the dose was first reduced
Measured: 24 weeks after dose-reduction
The radiographic progression of total Sharp van der Heijde score after 48 weeks from baseline
The primary efficacy outcome is the progression of total Sharp van der Heijde score after 48 weeks from BL
Measured: 48 weeks from BL
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2011 (estimated)
- Study start14 Dec 2012
- Primary completionJul 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 812 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ronald van Vollenhoven, prof., Karolinska Institutet
- Investigators
- Ronald van Vollenhoven, MD, Prof., Principal investigator, The Karolinska Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01491815
- Sponsor's protocol ID
- NORD-STAR
- Other IDs
- 2011-004720-35, 2011/2069-31/4
- Status last verified
- Jul 2022
- First submitted
- 8 Dec 2011
- Last updated
- 8 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Lend K, Twisk JWR, Koopman FA, Rudin A, Hetland ML, Uhlig T, Nordstrom DC, Nurmohamed MT, Gudbjornsson B, Horslev-Petersen K, Heiberg MS, Sokka-Isler T, Grondal G, Haavardsholm EA, Ostergaard M, Lampa J, van Vollenhoven R. Flare risk after oral glucocorticoid bridging with methotrexate or intra-articular bridging with triple therapy in early rheumatoid arthritis. J Intern Med. 2026 Jun;299(6):741-753. doi: 10.1111/joim.70094. Epub 2026 Apr 6.
PubMed 41943506Lampa J, Nordstrom D, van Vollenhoven R, Lund Hetland M, Haavardsholm EA, Ostergaard M, Rudin A, Heiberg MS, Nurmohamed M, Gudbjornsson B, Lend K, Horslev-Petersen K, Sokka-Isler T, Grondal G, Krabbe S, Lindqvist J, Gjertsson I, Glinatsi D, Kapetanovic M, Gentline C, Aga AB, Relas H, Lorenzen T, Cagnotto G, Back J, Hendricks O, Dijkshoorn B, Oberg K, Ljosa MK, Brodin E, Lindegaard HM, Soderbergh A, Rizk M, Kastbom A, Larsson P, Uhrenholt L, Just SA, Stevens DJ, Laurberg TB, Bakland G, Olsen IC, Sexton J, Uhlig T; NORD-STAR study group. Certolizumab pegol, abatacept, tocilizumab or active conventional therapy in early rheumatoid arthritis: 48-week patient-reported outcomes from the NORD-STAR trial. Lancet Rheumatol. 2026 Apr;8(4):e285-e294. doi: 10.1016/S2665-9913(26)00007-X.
PubMed 41881637Sellden T, Andersson K, Gjertsson I, Hultgard Ekwall AK, Lend K, Lund Hetland M, Ostergaard M, Uhlig T, Schrumpf Heiberg M, Nurmohamed MT, Lampa J, Sokka Isler T, Nordstrom D, Horslev-Petersen K, Gudbjornsson B, Grondal G, van Vollenhoven R, Maglio C, Lundell AC, Rudin A. Low Th2 and high PD1+ TFh cells in blood predict remission after CTLA-4Ig treatment for 48 weeks in early rheumatoid arthritis. PLoS One. 2025 Aug 28;20(8):e0330823. doi: 10.1371/journal.pone.0330823. eCollection 2025.
PubMed 40875656Lend K, Twisk JW, Kumar N, Dijkshoorn B, Lampa J, Rudin A, Hetland ML, Uhlig T, Nordstrom D, Ostergaard M, Gudbjornsson B, Sokka-Isler T, Grondal G, Horslev-Petersen K, Nurmohamed MT, Frostegard J, van Vollenhoven RF. Glucocorticoid treatment in early rheumatoid arthritis is independently associated with increased PCSK9 levels: data from a randomised controlled trial. RMD Open. 2025 Jun 5;11(2):e005129. doi: 10.1136/rmdopen-2024-005129.
PubMed 40480650Lend K, Lampa J, Padyukov L, Hetland ML, Heiberg MS, Nordstrom DC, Nurmohamed MT, Rudin A, Ostergaard M, Haavardsholm EA, Horslev-Petersen K, Uhlig T, Sokka-Isler T, Gudbjornsson B, Grondal G, Frazzei G, Christiaans J, Wolbink G, Rispens T, Twisk JWR, van Vollenhoven RF. Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial. Ann Rheum Dis. 2024 Nov 14;83(12):1657-1665. doi: 10.1136/ard-2024-226024.
PubMed 39079894Dubovyk V, Vasileiadis GK, Fatima T, Zhang Y, Kapetanovic MC, Kastbom A, Rizk M, Soderbergh A, Zhao SS, van Vollenhoven RF, Hetland ML, Haavardsholm EA, Nordstrom D, Nurmohamed MT, Gudbjornsson B, Lampa J, Ostergaard M, Heiberg MS, Sokka-Isler T, Grondal G, Lend K, Horslev-Petersen K, Uhlig T, Rudin A, Maglio C. Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study. RMD Open. 2024 Apr 4;10(2):e004227. doi: 10.1136/rmdopen-2024-004227.
PubMed 38580350Lend K, Koopman FA, Lampa J, Jansen G, Hetland ML, Uhlig T, Nordstrom D, Nurmohamed M, Gudbjornsson B, Rudin A, Ostergaard M, Heiberg MS, Sokka-Isler T, Horslev-Petersen K, Haavardsholm EA, Grondal G, Twisk JWR, van Vollenhoven R. Methotrexate Safety and Efficacy in Combination Therapies in Patients With Early Rheumatoid Arthritis: A Post Hoc Analysis of a Randomized Controlled Trial. Arthritis Rheumatol. 2024 Mar;76(3):363-376. doi: 10.1002/art.42730. Epub 2024 Jan 18.
PubMed 37846618Ostergaard M, van Vollenhoven RF, Rudin A, Hetland ML, Heiberg MS, Nordstrom DC, Nurmohamed MT, Gudbjornsson B, Ornbjerg LM, Boyesen P, Lend K, Horslev-Petersen K, Uhlig T, Sokka T, Grondal G, Krabbe S, Lindqvist J, Gjertsson I, Glinatsi D, Kapetanovic MC, Aga AB, Faustini F, Parmanne P, Lorenzen T, Giovanni C, Back J, Hendricks O, Vedder D, Rannio T, Grenholm E, Ljosa MK, Brodin E, Lindegaard H, Soderbergh A, Rizk M, Kastbom A, Larsson P, Uhrenholt L, Just SA, Stevens DJ, Bay Laurbjerg T, Bakland G, Olsen IC, Haavardsholm EA, Lampa J; NORD-STAR study group. Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial. Ann Rheum Dis. 2023 Oct;82(10):1286-1295. doi: 10.1136/ard-2023-224116. Epub 2023 Jul 9.
PubMed 37423647Stockfelt M, Lundell AC, Hetland ML, Ostergaard M, Uhlig T, Heiberg MS, Haavardsholm EA, Nurmohamed MT, Lampa J, Nordstrom D, Petersen KH, Gudbjornsson B, Grondal G, Aldridge J, Andersson K, Blennow K, Zetterberg H, van Vollenhoven R, Rudin A. Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial. Arthritis Res Ther. 2021 Jul 13;23(1):189. doi: 10.1186/s13075-021-02556-1.
PubMed 34256800Hetland ML, Haavardsholm EA, Rudin A, Nordstrom D, Nurmohamed M, Gudbjornsson B, Lampa J, Horslev-Petersen K, Uhlig T, Grondal G, Ostergaard M, Heiberg MS, Twisk J, Lend K, Krabbe S, Hyldstrup LH, Lindqvist J, Hultgard Ekwall AK, Gron KL, Kapetanovic M, Faustini F, Tuompo R, Lorenzen T, Cagnotto G, Baecklund E, Hendricks O, Vedder D, Sokka-Isler T, Husmark T, Ljosa MA, Brodin E, Ellingsen T, Soderbergh A, Rizk M, Olsson AR, Larsson P, Uhrenholt L, Just SA, Stevens DJ, Laurberg TB, Bakland G, Olsen IC, van Vollenhoven R; NORD-STAR study group. Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial. BMJ. 2020 Dec 2;371:m4328. doi: 10.1136/bmj.m4328.
PubMed 33268527Glinatsi D, Heiberg MS, Rudin A, Nordstrom D, Haavardsholm EA, Gudbjornsson B, Ostergaard M, Uhlig T, Grondal G, Horslev-Petersen K, van Vollenhoven R, Hetland ML. Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study. Trials. 2017 Apr 4;18(1):161. doi: 10.1186/s13063-017-1891-x.
PubMed 28376912
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Open-label, Blinded-assessor, Phase 4 Study in Patients With Early Rheumatoid Arthritis to Compare Active Conventional Therapy Versus Three Biologic Treatments, and Two De-escalation Strategies in Patients Who Respond to Treatment
- ClinicalTrials.gov ID
- NCT01491815
- Acronym / sponsor ID
- NORD-STAR
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 812 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Study start
- 14 Dec 2012 (actual)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 14 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an international (Sweden, Finland, Norway, Denmark, Iceland and the Netherlands) trial designed to compare the safety and efficacy of active conventional therapy (ACT) and three biologic treatments in subjects with early rheumatoid arthritis (RA). The global aim of this study is to assess and compare
- the proportion of subjects who achieve remission with ACT versus three different biologic therapies (Certolizumab-pegol, Abatacept or Tocilizumab)
- two alternative de-escalation strategies in patients who respond to first-line therapy.
Detailed description
After completed enrollment a total of 812 patients were included in the study.
371 of the included patients have entered treatment part 2, 256 patients have exited the study after treatment part 1, 207 patients have had early termination and 322 patients have completed the full study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Active conventional therapy (ACT) | Active comparator | Drug: Non-biological DMARD'sNon-biological DMARD's: Methotrexate plus steroids or Methotrexate plus Sulphasalazine and Hydroxychloroquine and steroids |
| Biologic agent 1 | Active comparator | Biological: CimziaCimzia: Certolizumab-pegol plus Methotrexate and steroids |
| Biologic agent 2 | Active comparator | Biological: OrenciaOrencia: Abatacept plus Methotrexate and steroids |
| Biologic agent 3 | Active comparator | Biological: RoActemraRoActemra: Tocilizumab plus Methotrexate and steroids |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Subject is ≥18 years of age.
- Subject has a diagnosis of RA as defined by the newly established ACR/EULAR criteria, 2010. (Patients should also be classified according to the 1987-revised ACR-classification criteria, without this being an inclusion criteria).
- <24 months from arthritis symptom debut (symptom duration will be registered).
- Subject must have DAS28 (CRP) > 3.2.
- ≥ 2 swollen joints AND ≥ 2 tender joints.
Key exclusion criteria (33 listed)
- Subject has been previously treated with disease modifying antirheumatic drugs (DMARDs) for rheumatic diseases.
- Current active inflammatory joint disease other than RA.
- Subjects has had a dose of prednisone (or equivalent) >7.5 mg/day or has had a dose change within the preceding 4 weeks.
- Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks. Inhaled corticosteroids for stable medical conditions are allowed.
- Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-biological DMARD'sMethotrexate: 25mg/week. SSZ: 2 g/day. HCQ: 35 mg/kg/week (Finland and Denmark) Methotrexate: 25mg/week. Prednisolone 20 mg/day tapered in 9 weeks to 5 mg/day, discontinued after 9 months. (Sweden, Norway, Iceland, and the Netherlands) | Drug | Active conventional therapy (ACT) |
| CimziaCertolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week | Biological | Biologic agent 1 |
| OrenciaAbatacept: 125 mg s.c. every week. Methotrexate: 25mg/week | Biological | Biologic agent 2 |
| RoActemraTocilizumab is given as 4-weekly infusions at dosage 8 mg/kg or 162 mg in solution s.c. every week. Methotrexate: 25mg/week | Biological | Biologic agent 3 |
Primary outcome
The proportion of patients in remission at week 24 from baseline according to CDAI
Time frame: 24 weeks from BL
Treatment Part 1: The primary efficacy outcome is the proportion of patients in remission at week 24 from BL according to CDAI
The proportion of patients in remission at week 24 after dose-reduction according to CDAI
Time frame: 24 weeks after dose-reduction
Treatment Part 2: The primary efficacy outcome is the proportion of patients in remission according to CDAI, at the time point 24 weeks after the dose was first reduced
The radiographic progression of total Sharp van der Heijde score after 48 weeks from baseline
Time frame: 48 weeks from BL
The primary efficacy outcome is the progression of total Sharp van der Heijde score after 48 weeks from BL
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2022.
- Derived from this study: PubMed 41943506Lend K, Twisk JWR, Koopman FA, Rudin A, Hetland ML, Uhlig T, Nordstrom DC, Nurmohamed MT, Gudbjornsson B, Horslev-Petersen K, Heiberg MS, Sokka-Isler T, Grondal G, Haavardsholm EA, Ostergaard M, Lampa J, van Vollenhoven R. Flare risk after oral glucocorticoid bridging with methotrexate or intra-articular bridging with triple therapy in early rheumatoid arthritis. J Intern Med. 2026 Jun;299(6):741-753. doi: 10.1111/joim.70094. Epub 2026 Apr 6.
- Derived from this study: PubMed 41881637Lampa J, Nordstrom D, van Vollenhoven R, Lund Hetland M, Haavardsholm EA, Ostergaard M, Rudin A, Heiberg MS, Nurmohamed M, Gudbjornsson B, Lend K, Horslev-Petersen K, Sokka-Isler T, Grondal G, Krabbe S, Lindqvist J, Gjertsson I, Glinatsi D, Kapetanovic M, Gentline C, Aga AB, Relas H, Lorenzen T, Cagnotto G, Back J, Hendricks O, Dijkshoorn B, Oberg K, Ljosa MK, Brodin E, Lindegaard HM, Soderbergh A, Rizk M, Kastbom A, Larsson P, Uhrenholt L, Just SA, Stevens DJ, Laurberg TB, Bakland G, Olsen IC, Sexton J, Uhlig T; NORD-STAR study group. Certolizumab pegol, abatacept, tocilizumab or active conventional therapy in early rheumatoid arthritis: 48-week patient-reported outcomes from the NORD-STAR trial. Lancet Rheumatol. 2026 Apr;8(4):e285-e294. doi: 10.1016/S2665-9913(26)00007-X.
- Derived from this study: PubMed 40875656Sellden T, Andersson K, Gjertsson I, Hultgard Ekwall AK, Lend K, Lund Hetland M, Ostergaard M, Uhlig T, Schrumpf Heiberg M, Nurmohamed MT, Lampa J, Sokka Isler T, Nordstrom D, Horslev-Petersen K, Gudbjornsson B, Grondal G, van Vollenhoven R, Maglio C, Lundell AC, Rudin A. Low Th2 and high PD1+ TFh cells in blood predict remission after CTLA-4Ig treatment for 48 weeks in early rheumatoid arthritis. PLoS One. 2025 Aug 28;20(8):e0330823. doi: 10.1371/journal.pone.0330823. eCollection 2025.
- Derived from this study: PubMed 40480650Lend K, Twisk JW, Kumar N, Dijkshoorn B, Lampa J, Rudin A, Hetland ML, Uhlig T, Nordstrom D, Ostergaard M, Gudbjornsson B, Sokka-Isler T, Grondal G, Horslev-Petersen K, Nurmohamed MT, Frostegard J, van Vollenhoven RF. Glucocorticoid treatment in early rheumatoid arthritis is independently associated with increased PCSK9 levels: data from a randomised controlled trial. RMD Open. 2025 Jun 5;11(2):e005129. doi: 10.1136/rmdopen-2024-005129.
- Derived from this study: PubMed 39079894Lend K, Lampa J, Padyukov L, Hetland ML, Heiberg MS, Nordstrom DC, Nurmohamed MT, Rudin A, Ostergaard M, Haavardsholm EA, Horslev-Petersen K, Uhlig T, Sokka-Isler T, Gudbjornsson B, Grondal G, Frazzei G, Christiaans J, Wolbink G, Rispens T, Twisk JWR, van Vollenhoven RF. Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial. Ann Rheum Dis. 2024 Nov 14;83(12):1657-1665. doi: 10.1136/ard-2024-226024.
- Derived from this study: PubMed 38580350Dubovyk V, Vasileiadis GK, Fatima T, Zhang Y, Kapetanovic MC, Kastbom A, Rizk M, Soderbergh A, Zhao SS, van Vollenhoven RF, Hetland ML, Haavardsholm EA, Nordstrom D, Nurmohamed MT, Gudbjornsson B, Lampa J, Ostergaard M, Heiberg MS, Sokka-Isler T, Grondal G, Lend K, Horslev-Petersen K, Uhlig T, Rudin A, Maglio C. Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study. RMD Open. 2024 Apr 4;10(2):e004227. doi: 10.1136/rmdopen-2024-004227.
- Derived from this study: PubMed 37846618Lend K, Koopman FA, Lampa J, Jansen G, Hetland ML, Uhlig T, Nordstrom D, Nurmohamed M, Gudbjornsson B, Rudin A, Ostergaard M, Heiberg MS, Sokka-Isler T, Horslev-Petersen K, Haavardsholm EA, Grondal G, Twisk JWR, van Vollenhoven R. Methotrexate Safety and Efficacy in Combination Therapies in Patients With Early Rheumatoid Arthritis: A Post Hoc Analysis of a Randomized Controlled Trial. Arthritis Rheumatol. 2024 Mar;76(3):363-376. doi: 10.1002/art.42730. Epub 2024 Jan 18.
- Derived from this study: PubMed 37423647Ostergaard M, van Vollenhoven RF, Rudin A, Hetland ML, Heiberg MS, Nordstrom DC, Nurmohamed MT, Gudbjornsson B, Ornbjerg LM, Boyesen P, Lend K, Horslev-Petersen K, Uhlig T, Sokka T, Grondal G, Krabbe S, Lindqvist J, Gjertsson I, Glinatsi D, Kapetanovic MC, Aga AB, Faustini F, Parmanne P, Lorenzen T, Giovanni C, Back J, Hendricks O, Vedder D, Rannio T, Grenholm E, Ljosa MK, Brodin E, Lindegaard H, Soderbergh A, Rizk M, Kastbom A, Larsson P, Uhrenholt L, Just SA, Stevens DJ, Bay Laurbjerg T, Bakland G, Olsen IC, Haavardsholm EA, Lampa J; NORD-STAR study group. Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial. Ann Rheum Dis. 2023 Oct;82(10):1286-1295. doi: 10.1136/ard-2023-224116. Epub 2023 Jul 9.
- Derived from this study: PubMed 34256800Stockfelt M, Lundell AC, Hetland ML, Ostergaard M, Uhlig T, Heiberg MS, Haavardsholm EA, Nurmohamed MT, Lampa J, Nordstrom D, Petersen KH, Gudbjornsson B, Grondal G, Aldridge J, Andersson K, Blennow K, Zetterberg H, van Vollenhoven R, Rudin A. Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial. Arthritis Res Ther. 2021 Jul 13;23(1):189. doi: 10.1186/s13075-021-02556-1.
- Derived from this study: PubMed 33268527Hetland ML, Haavardsholm EA, Rudin A, Nordstrom D, Nurmohamed M, Gudbjornsson B, Lampa J, Horslev-Petersen K, Uhlig T, Grondal G, Ostergaard M, Heiberg MS, Twisk J, Lend K, Krabbe S, Hyldstrup LH, Lindqvist J, Hultgard Ekwall AK, Gron KL, Kapetanovic M, Faustini F, Tuompo R, Lorenzen T, Cagnotto G, Baecklund E, Hendricks O, Vedder D, Sokka-Isler T, Husmark T, Ljosa MA, Brodin E, Ellingsen T, Soderbergh A, Rizk M, Olsson AR, Larsson P, Uhrenholt L, Just SA, Stevens DJ, Laurberg TB, Bakland G, Olsen IC, van Vollenhoven R; NORD-STAR study group. Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial. BMJ. 2020 Dec 2;371:m4328. doi: 10.1136/bmj.m4328.
- Derived from this study: PubMed 28376912Glinatsi D, Heiberg MS, Rudin A, Nordstrom D, Haavardsholm EA, Gudbjornsson B, Ostergaard M, Uhlig T, Grondal G, Horslev-Petersen K, van Vollenhoven R, Hetland ML. Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study. Trials. 2017 Apr 4;18(1):161. doi: 10.1186/s13063-017-1891-x.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald van Vollenhoven, MD, Prof. principal investigator
The Karolinska Institute
30 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Non-biological DMARD's, Cimzia and Orencia in people with Rheumatoid Arthritis, run by Karolinska Institutet at 30 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Sweden, Denmark, Norway, Finland, Iceland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of patients in remission at week 24 from baseline according to CDAI (time frame: 24 weeks from BL). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01491815, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2022.