Dose Reduction for Early Rheumatoid Arthritis Patients With Low Disease Activity

Study Overview
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Brief Summary
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This is an international (Nordic) trial designed to compare the safety and efficacy of active conventional therapy (ACT) and three biologic treatments (Certolizumab-pegol, Abatacept or Tocilizumab) in subjects with early rheumatoid arthritis (RA). The global aim of this study is to assess and compare two alternative de-escalation strategies in patients who achieved low disease activity during first-line therapy in the NORD-STAR study.

Detailed Description
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25 patients have been included in the study of which 1 has had an early termination an 22 have completed the full study.

Official Title
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A Multicenter, Randomized, Open-label, Blinded-assessor, Follow-up, Phase 4 Study in Patients With Rheumatoid Arthritis Who Have Completed the Initial Treatment Part in the NORD-STAR Study and Have Reached Stable Low Disease Activity

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Sulphasalazine + Hydroxychloroquine OR Prednisolone
* Biological: Cimzia
* Biological: Orencia
* Biological: RoActemra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has been enrolled in the NORD-STAR study according to that study inclusion criteria (and did not meet any of the exclusion criteria in that study). Subject has low-disease-activity according to: 2.8 < CDAI ≤ 10.0, from week 56 in the NORD-STAR study, i.e. during 24 weeks before randomization. Subject has not more than 3 tender out of the 28 joints. According to the investigators opinion the remaining findings are not due to significant active disease (RA). 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 Subject is judged to be in good general health as determined by the principal investigator. Subject must be able and willing to provide written informed consent and comply with the requirements of this study protocol. Exclusion Criteria: Subject has left the NORD-STAR study due to moderate or high disease activity (CDAI ≥ 10.0) or for other medically important event(s). Patient is eligible for treatment part 2 (A or B) in the NORD-STAR study. Active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization within 4 weeks prior to randomization. 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 randomization. Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (i.v.) anti-infectives within 30 days or oral anti-infectives within 14 days prior to randomization. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Patients keep the intervention they had in the NORD-STAR-study (NCT01491815), i.e. one of the four below: Sulphasalazine + Hydroxychloroquine OR Prednisolone plus Methotrexate and steroids Cimzia plus Methotrexate and steroids Orencia plus Methotrexate and steroids RoActemra plus Methotrexate and steroids This intervention is de-escalated starting at randomization. | Drug: Sulphasalazine + Hydroxychloroquine OR Prednisolone<br>* 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, and Iceland)<br>* Other names: SSZ+HCQ or Prednisolone;Biological: Cimzia<br>* Certolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week<br>* Other names: Certolizumab-pegol;Biological: Orencia<br>* Abatacept: 125 mg s.c. every week. Methotrexate: 25mg/week<br>* Other names: Abatacept;Biological: RoActemra<br>* Tocilizumab is given as 4-weekly infusions at dosage 8 mg/kg or 162 mg in solution s.c. every week. Methotrexate: 25mg/week<br>* Other names: Tocilizumab;|
| Active Comparator: Arm 2<br>Patients keep the intervention they had in the NORD-STAR-study (NCT01491815), i.e. one of the four below: Sulphasalazine + Hydroxychloroquine OR Prednisolone plus Methotrexate and steroids Cimzia plus Methotrexate and steroids Orencia plus Methotrexate and steroids RoActemra plus Methotrexate and steroids This intervention is de-escalated starting 24 weeks after randomization. | Drug: Sulphasalazine + Hydroxychloroquine OR Prednisolone<br>* 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, and Iceland)<br>* Other names: SSZ+HCQ or Prednisolone;Biological: Cimzia<br>* Certolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week<br>* Other names: Certolizumab-pegol;Biological: Orencia<br>* Abatacept: 125 mg s.c. every week. Methotrexate: 25mg/week<br>* Other names: Abatacept;Biological: RoActemra<br>* Tocilizumab is given as 4-weekly infusions at dosage 8 mg/kg or 162 mg in solution s.c. every week. Methotrexate: 25mg/week<br>* Other names: Tocilizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients maintaining low disease activity after dose reduction | The proportion of patients, with early dose reduction vs late dose reduction, who maintain low disease activity (2.8 < CDAI ≤ 10.0) at the time point 24 weeks after the dose was first reduced. | 24 weeks after dose reduction |