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.
ID
Source
Brief title
Condition
- Synovial and bursal disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
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, RF-status, 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 frequency of serious adverse events (SAEs) between 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) between 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)
Overall:
- The predictive value of the patient reported Routine Assessment of Patient
Index Data 3 (RAPID3, performed monthly) to detect DAS28-remission and -flare
(evaluated 3-monthly).
Background summary
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.
Study 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
We will perform a multicenter, open label clinical trial in very early RA
patients. Remission will be induced by an open label T2T remission induction
protocol in clinical care. Patients in sustained remission on MTX/GOL will be
randomized to taper either MTX first, then GOL or GOL first, then MTX.
Intervention
Remission will be induced by a combination of MTX, hydroxychloroquine (HCQ),
i.m. glucocorticoids (GC), and, if not in remission, the TNFi golimumab (GOL)
(phase I).
Patients in sustained remission 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:
- Group A: Taper and stop GOL first during 24 weeks, then, if still in
sustained remission, taper and stop MTX during 24 weeks
- Group B: Taper and stop MTX first during 24 weeks, then, if still in
sustained remission, taper and stop GOL during 24 weeks
During 1 year additional follow-up maintenance of drug-free sustained
remission will be investigated (phase III).
Study burden and risks
The study visits will be performed in combination with 3-monthly scheduled
visits to the outpatient clinic in usual care. Patients will be treated
according to a treat-to-target strategy. In addition to usual care, patients
will fill in questionnaires: HAQ, EQ-5D, HADS, FACIT-F, RAPID3, and a health
care utilization and work participation questionnaire. No increased risks are
associated with the randomised tapering strategy as clinical studies performed
so far have shown reasonable results for tapering TNFi for patients in
remission. Importantly, remission can be reached again in most of the patients
who flare during the tapering phase or after withdrawal of TNFi after
retreatment. This is current clinical practice. Moreover, patients tapering or
discontinuing MTX during TNFi treatment generally have comparable DAS28 scores
and TNFi drug survival as those who continue MTX treatment.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
To be eligible to participate in this study, a subject must meet all of the following criteria:
- Able and willing to give written informed consent
- At least 18 years of age
- Fulfilling 2010 ACR/EULAR criteria for RA (Appendix A.)
- Patient reported symptom duration (joint stiffness, tenderness, pain, and/or swelling) < 12 months
- Naïve for DMARD and biological treatment
- DAS28 <=>3.2
- Have sufficient knowledge of the Dutch language to be able to comply with the requirements of the study protocol
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Having used glucocorticoids < 6 weeks before the baseline visit
- Being pregnant (based on anamnesis) or a nursing women or a women of child bearing potential without (adequate) use of contraception
- Having any other inflammatory rheumatic disease than RA, except for secondary Sjögren*s syndrome
- Having contraindications for the use of MTX/HCQ/methylprednisolone/GOL.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-004858-17-NL |
| CCMO | NL55647.041.16 |