Track topics on Twitter Track topics that are important to you
Rheumatoid arthritis (RA) patients in remission with a combination of TNFinhibitors (TNFi) and methotrexate (MTX) often express their wish to stop MTX treatment because of side effects. Given the efficacy of TNFi it is conceivable that in early RA patients in remission with methotrexate (MTX)/TNFi stepwise discontinuation of MTX prior to TNFi is superior in maintaining sustained remission and reaching drug free remission as compared to discontinuation of TNFi prior to MTX.
Objective: To investigate whether tapering MTX first, then the TNFi golimumab (GOL), is more efficacious than tapering GOL first, then MTX, in sustaining remission and reaching drug free remission.
Study design: multicenter, open label clinical trial in very early RA patients. Remission will be induced by an open label treat-to-target (T2T) remission induction protocol in clinical care: (MTX, hydroxychloroquine (HCQ), i.m. glucocorticoids (GC), and, if not in remission, the TNFi golimumab (GOL)) (phase I, 3/4th or 1 year). Patients in sustained remission on MTX/GOL (DAS28<2.6 with max 4 swollen joints of the 44 swollen joint count (SJC) at 2 consecutive visits 3 months apart) will be randomized to taper either MTX first, then GOL or GOL first, then MTX with as primary endpoint sustained (drug free) remission (phase II, 1 year). During 1 year additional follow-up maintenance of drug-free sustained remission will be investigated (phase III).
Study population: RA patients fulfilling 2010 American College of Rheumatology (ACR)/EUropean League Against Rheumatism (EULAR) criteria for RA, with symptom duration <12 months; naïve for anti-rheumatic drugs and glucocorticoids for RA; DAS28 ≥3.2.
Intervention: Patients in sustained remission (defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at ≥ 2 consecutive visits 3 months apart) on MTX/GOL at the end of phase I (after 24 weeks of treatment with MTX/GOL) will be randomized in a ratio of 1:1 to taper medication as follows:
- Taper and stop GOL first during 24 weeks, then, if still in sustained remission, taper and stop MTX during 24 weeks
- Taper and stop MTX first during 24 weeks, then, if still in sustained remission, taper and stop GOL during 24 weeks The primary end point is the proportion of patients in sustained remission at week 24 after start of tapering of either MTX or GOL first. The main secondary end point is the proportion of patients in drug-free sustained remission, at week 48 after start of tapering.
Phase I (Remission induction):
- The proportion of patients on MTX/HCQ/GC in remission, defined as DAS28<2.6, at week 12 or week 24 after start of treatment.
- The proportion of patients on MTX/GOL in sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart, at week 24 after start of GOL treatment.
- Predictors of remission upon treatment with MTX, HCQ and a single injection of i.m. GC (e.g. smoking status, BMI, alcohol use, sex, disease duration, DAS28, Rheumatoid Factor (RF) -status, Anti-citrullinated protein antibody (ACPA) -status, presence of erosions)
- Predictors of remission upon treatment with MTX and GOL (e.g. smoking status, BMI, alcohol use, sex, disease duration, DAS28, RF-status, ACPA-status, presence of erosions)
Phase II (Tapering):
- The proportion of patients in sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart, at week 48 after start of tapering MTX first, then GOL or GOL first, then MTX.
- The proportion of patients in drug-free sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart while off anti-rheumatic treatment, at week 48 after start of tapering
- Mean disease activity, using the disease activity score assessing 28 joints (DAS28), at week 24 and week 48 after start of tapering
- Mean functional ability, using the Dutch consensus health assessment questionnaire (HAQ), at week 24 and week 48 after start of tapering
- Mean quality of life, using the visual analogue scale (VAS) of the EuroQol 5 dimensions (EQ5D) questionnaire, at week 24 and week 48 after start of tapering
- Mean anxiety and depression (using the Hospital Anxiety and Depression Scale (HADS)), at week 24 and week 48 after start of tapering
- Mean fatigue (using the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F)), at week 24 and week 48 after start of tapering
- The proportion of serious adverse events (SAEs) in the two tapering strategies after 24 and after 48 weeks.
- The time until remission (DAS28<2.6) after retreatment with the last effective dose upon flare while tapering MTX/GOL.
Phase III (Follow-up):
- The proportion of patients in drug-free sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart while off anti-rheumatic treatment, at week 48 after discontinuation of both MTX and GOL
- The time until remission, defined as DAS28<2.6, after retreatment in clinical care upon flare
- The proportion of serious adverse events (SAEs) in the two tapering strategies at week 24 and week 48.
Phase II and III:
- Cost per extra patient in remission up to week 96 after start of tapering (end of phase III)
- Cost per Quality Adjusted life Year (QALY) gained up to week 96 after start of tapering (end of phase III)
- The sensitivity and predictive value of the patient reported Routine Assessment of Patient Index Data 3 (RAPID3) to detect remission and flare
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Not yet recruiting
Published on BioPortfolio: 2016-10-18T02:08:21-0400
Little is currently known as to the predictive value of ultrasound in guiding the decision to taper drug treatment in patients with stable rheumatoid arthritis, nor the influence that pati...
The purpose of this study is to compare the incidence rates of infection, malignancy and death among patients with rheumatoid arthritis who are treated with abatacept and those who are tre...
Objective: To evaluate what factors contribute to activity limitations in subjects with rheumatoid arthritis considering the International Classification of Functioning, Disability and Hea...
Patients with rheumatoid arthritis are at increased risk of having cardiovascular deaths. Our study is aimed at looking at the effects of proven cholesterol lowering treatment drug called ...
This study will look at whether this new drug is effective in the treatment of rheumatoid arthritis, and at whether it is safe and well-tolerated by patients with the disease.
Validity of the Rheumatoid Arthritis Impact of Disease (RAID) score and definition of cut-off points for disease activity states in a population-based European cohort of patients with rheumatoid arthritis.
To assess the validity of the Rheumatoid Arthritis Impact of Disease (RAID) for measuring disease activity of rheumatoid arthritis (RA), and to determine cut-off values for defining the disease activi...
The RACAT (Rheumatoid Arthritis Comparison of Active Therapies) trial found triple therapy to be noninferior to etanercept-methotrexate in patients with active rheumatoid arthritis (RA).
To examine the prevalence of alpha-1 antitrypsin (AAT) deficiency (AATD) in rheumatoid arthritis (RA), and to determine if AATD is associated with higher levels of rheumatoid factor (RF), antinuclear ...
The objective was to explore the link between a patient acceptable symptom state (PASS) and patient-perceived impact in rheumatoid arthritis (RA) and psoriatic arthritis (PsA).
Arthritis in children, with onset before 16 years of age. The terms juvenile rheumatoid arthritis (JRA) and juvenile idiopathic arthritis (JIA) refer to classification systems for chronic arthritis in children. Only one subtype of juvenile arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.
Rheumatoid arthritis of children occurring in three major subtypes defined by the symptoms present during the first six months following onset: systemic-onset (Still's Disease, Juvenile-Onset), polyarticular-onset, and pauciarticular-onset. Adult-onset cases of Still's disease (STILL'S DISEASE, ADULT-ONSET) are also known. Only one subtype of juvenile rheumatoid arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.
A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.
Systemic-onset rheumatoid arthritis in adults. It differs from classical rheumatoid arthritis in that it is more often marked by acute febrile onset, and generalized lymphadenopathy and hepatosplenomegaly are more prominent.
Antibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS.
Arthroplasty Joint Disorders Orthopedics Spinal Cord Disorders Orthopedics is the science or practice of correcting deformities caused by disease or damage to the bones and joints of the skeleton. This specialized branch of surgery may ...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...