Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Remission, Dose reduction
Brief summary
This is a phase 3, multicenter, randomized, open, prospective, controlled, parallel-group intervention study in 318 patients with Rheumatoid Arthritis. The study is composed of 3 phases: a pre-randomization phase for up to 10 days followed by a 1-year randomized, open three arm treatment phase for each patient, followed by a 5-year observational phase for all patients still in remission.
Detailed description
Rheumatoid Arthritis (RA) is characterized by progressive synovitis leading to degradation of articular cartilage leading to erosions in juxtaarticular bones driven by auto antibodies. Few clinical studies could show that quick and thorough control of inflammatory processes could stop degradation processes \[17, 18, 19, 20, 21\] and had presumably better prognosis of remission than untreated and/or uncontrolled RA disease \[20\]. These studies aimed at low disease activity \[20\], often focused on early RA \[18, 19\], evaluating different therapy strategies, mostly escalating instead of deescalating medications \[20, 21\]. Real RA- in - remission or therapy reduction studies are missing up to now, even if first small trials focusing on one preparation showed promising results \[16, 17\]. In this study all conventional medications in usual combinations are being evaluated for the treatment of Rheumatoid Arthritis in different stages of disease duration. The study is scheduled as a 365-day (12-months), phase 3 multicenter, randomized, open, prospective, controlled, parallel-group intervention study in 318 patients with Rheumatoid Arthritis. Based on the results of the clinical studies mentioned above, and the need for a guideline with therapy proposals for RA- patients in remission all current preparations will be evaluated in subjects under the controlled setting of a clinical study. The information obtained from this study will assess the formulation of new guidelines regarding patients with Rheumatoid Arthritis in remission.
Interventions
DRUGControl group
Stable dosage of previous treatment with Decortin H®, Leflunomid (e.g. Arava®), Ciclosporin (e.g. Immunosporin®), Sulfasalazin (e.g. Azulfidine RA®, Pleon RA®), Hydroxychloroquine (e.g. Quensyl®); Azathioprin, Methotrexate (e.g. Lantarel®, Metex®), Etanercept (Enbrel®), Adalimumab (Humira®), Infliximab (Remicade®), Tocilizumab (RoActemra®), Golimumab (Simponi®), Certolizumab (Cimzia®), Abatacept (Orencia®)
OTHERReduction group 1
Dose reduction of 50% for 12 months of previous treatment with Decortin H®, Leflunomid (e.g. Arava®), Ciclosporin (e.g. Immunosporin®), Sulfasalazin (e.g. Azulfidine RA®, Pleon RA®), Hydroxychloroquine (e.g. Quensyl®); Azathioprin, Methotrexate (e.g. Lantarel®, Metex®), Etanercept (Enbrel®), Adalimumab (Humira®), Infliximab (Remicade®), Tocilizumab (RoActemra®), Golimumab (Simponi®), Certolizumab (Cimzia®), Abatacept (Orencia®)
OTHERReduction group 2
Dose reduction of 50% of previous treatment with Decortin H®, Leflunomid (e.g. Arava®), Ciclosporin (e.g. Immunosporin®), Sulfasalazin (e.g. Azulfidine RA®, Pleon RA®), Hydroxychloroquine (e.g. Quensyl®); Azathioprin, Methotrexate (e.g. Lantarel®, Metex®), Etanercept (Enbrel®), Adalimumab (Humira®), Infliximab (Remicade®), Tocilizumab (RoActemra®), Golimumab (Simponi®), Certolizumab (Cimzia®), Abatacept (Orencia®) for 6 months and if they are still in remission therapy will be discontinued.
Sponsors
University of Erlangen-Nürnberg Medical School
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must understand and voluntarily sign an informed consent form including written consentfor data protection * Must be able to adhere to the study visit schedule and other protocol requirements * Must be male or female and aged ≥ 18 years at time of consent * Must have a diagnosis of RA according to ACR criteria \[26\] for at least 12 months * Must have a DAS 28 score of less than 2.6 (means: remission) at randomization (documented in at least three subsequent controls for six months; compare figure three in the appendix for details) * At screening-visit patients should have been treated without alterations of therapy for at least six months with one of the following therapies: (i) one or more of the following conventional DMARDS (with or without concomitant use of glucocorticoids): Methotrexate, Leflunomide, Ciclosporine A, Sulfasalazine, Azathioprine or Hydroxychloroquine, (ii) a combination of a conventional DMARD (Methotrexate, Leflunomide, Ciclosporine A, Sulfasalazine, Azathioprine or Hydroxychloroquine) with one of the following biologicals (with or without concomitant use of glucocorticoids): Infliximab, Adalimumab, Etanercept, Tocilizumab, Golimumab, Certolizumab, Abatacept, (iii) or one of the biologicals mentioned above without combination with a conventional DMARD. All of the aforementioned biologicals are also allowed in combination with glucocorticoids, (iv) monotherapy treatment with glucocorticoids (without any DMARD or biological treatment).
Exclusion criteria
* Treatment with Rituximab during the last 12 months before screening * Intake of a daily dosage of more than 5mg Prednisolone - equivalent during the last 6 months before randomization; intraarticular injections of glucocorticoids do not represent an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects in each treatment group who are still in remission after 12 months (remission defined as DAS 28 < 2.6) reduction or even discontinuation in RA-patients after achievement of long lasting remission. | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects in each treatment group who are still in remission after 3, 6, 9 months (remission defined according to Pinals - criteria) | 12months |
| Proportion of subjects in each treatment group with increased disease activity | 12 months |
| Proportion of adverse events (to be documented via unscheduled visit-sheet) | 12 months |
| DAS 28 after 3, 6, 9 and 12 months | 12 months |
| CRP after 3, 6, 9 and 12 months | 12 months |
| ESR after 3, 6, 9 and 12 months | 12 months |
| Swollen joint counts after 3, 6, 9 and 12 months | 12 months |
| Tender joint counts after 3, 6, 9 and 12 months | 12 months |
| Patient self assessment of pain (VAS) after 3, 6, 9 and 12 months | 12 months |
| Proportion of subjects in each treatment group who are still in remission after 3, 6, 9 months (remission defined as DAS 28 < 2.6). | 12 months |
| Duration of joint stiffness after 3, 6, 9 and 12 months | 12 months |
| HAQ (Health Assessment Questionnaire) after 3, 6, 9 and 12 months | 12 months |
| SF-36 (Short Form) Score after 3, 6, 9 and 12 months | 12 months |
| Coping-Questionnaire after 3, 6, 9 and 12 months | 12 months |
| PASS (patient acceptable symptom state) after 3, 6, 9 and 12 months | 12 months |
| WPAI:RA (Work Productivity and Activity Impairment Questionnaire) after 3, 6, 9, 12 months | 12 months |
| BDI - II (Beck-Depression Inventory) after 3, 6, 9 and 12 months | 12 months |
| Flare Questionnaire RA (German version): At time of potential flare | 12 months |
| Physician's and patient's assessment of global disease activity (VAS) after 3, 6, 9 and 12 months | 12 months |
Countries
Germany
Contacts
Primary ContactGeorg Schett, Prof. Dr. univ.
Backup ContactJuergen Rech, Dr. med.
Outcome results
None listed