Rheumatoid ArthritisPhase 4TOLEDONCT01557374
TOward the Lowest Effective DOse of Abatacept or Tocilizumab
A Phase 4 study testing Tocilizumab, Abatacept and Decrease Tocilizumab, Abatacept in people with Rheumatoid Arthritis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Ever since the biotherapy agents have entered the market, the recommended therapeutic objective in Rheumatoid arthritis, has been remission. Once obtained, it is advised to try to reduce or cease these biotherapy agents, for which, their efficacy is counterbalanced to their tolerance in the medium and long term as… 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?
- Tocilizumab, Abatacept and Decrease Tocilizumab, Abatacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 232 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2012to 8 Nov 2019
- 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
- Patients of at least 18 years old.
- Patients with RA, defined by ACR-EULAR 2010 criteria
- Treated for at least 1 year with Abatacept or Tocilizumab with market authorized doses*, and possibly with a DMARD and ≤ 5 mg per day of corticoids.
- In remission since at least 6 months according to ACR/ EULAR 2010 remission criteria or a DAS 28 ≤ 2.6**
- Without destructive structural progression during the previous year on the hand and feet x-rays (judged by the reference rheumatologist)
- Informed on the study and have given their acknowledged written consent to participate in the study.
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- Having had a prior medical visit.
- Prescribed dose stability (a spacing related to an infection or a surgery is not a prescribed dose spacing).
- An increase in inflammatory parameters and pain due to an intercurrent event must be distinguished from the RA activity increasing.
Who cannot join
- Already included in another treatment evaluation trial for the same pathology.
- Surgical intervention programmed for in the next 24 months to come.
- Pregnancy or it's anticipation in the next 24 months to come.
- Non comprehension of French language.
- Non affiliation to social security.
- Patients under legal guardianship.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Tapering Abatacept or Tocilizumab in Rheumatoid Arthritis in Remission. An Evaluation of Disease Activity, Relapse Risk, Structural Progression and the Economic Impact of a Tapering Strategy
Ever since the biotherapy agents have entered the market, the recommended therapeutic objective in Rheumatoid arthritis, has been remission. Once obtained, it is advised to try to reduce or cease these biotherapy agents, for which, their efficacy is counterbalanced to their tolerance in the medium and long term as well as their high price. Nevertheless, we do not dispose considerable data on the risks of relapse or structural progression during such a step down strategy. A few studies on anti-TNF agents have shown the possibility of such therapy reduction. A national study, " STRASS ", coordinated by Bruno FAUTREL, has evaluated the possibility of spacing or even stopping the injections of anti-TNF(s). To date, no data concerning Abatacept or Tocilizumab has been published.
As the expected result, this study is aimed to test the feasibility of a step down strategy on 2 biological agents, Abatacept and Tocilizumab, in RA patients in remission.
Read the detailed description
Ever since the biotherapy agents have entered the market, the recommended therapeutic objective in Rheumatoid arthritis, has been remission. Once obtained, it is advised to try to reduce or cease these biotherapy agents, for which, their efficacy is counterbalanced to their tolerance in the medium and long term as well as their high price.
Nevertheless, we do not dispose considerable data on the risks of relapse or structural progression during such a step down strategy. A few studies on anti-TNF agents have shown the possibility of such therapy reduction. A national study, " STRASS ", coordinated by Bruno FAUTREL, has evaluated the possibility of spacing then stopping the injections of anti-TNF(s). To date, no data concerning Abatacept or Tocilizumab has been published.
This is a Non inferiority, prospective, randomized, controlled study with PROBE (Prospective Randomized, Open Blinded Evaluation) evaluating method.
The objectives of this study are:
- For patients with Rheumatoid Arthritis (RA) in remission under Abatacept or Tocilizumab, to evaluate in terms of disease activity within a 2 years period, the impact of a progressive decreasing biotherapy strategy (by progressively spacing the injections) in comparison with usual treatment (maintaining the usual dose and injection frequency of the biotherapeutic agent).
- To evaluate the impact of such decreasing strategy in terms of RA relapses and structural progression in 1 and 2 years.
- To determine the cost-effectiveness ratio of decreasing in comparison with maintaining the biological treatments.
Inclusion criteria:
Patients with RA, defined by ACR-EULAR 2010 criteria:
- Treated for at least 1 year with Abatacept or Tocilizumab with market authorized doses*, and possibly with a DMARD and ≤ 5 mg per day of corticoids.
- In remission for at least 6 months according to ACR/ EULAR 2010 remission criteria or a DAS 28 ≤ 2.6**
Patients are divided into 2 groups:
- Maintaining strategy: to maintain the biological treatment and possibly the associated DMARD and corticoids.
- Decreasing strategy: to decrease progressively the biological agent via progressively increasing the injection intervals, following a predetermined pattern, established according to the RA activity level, during each trimestrial visit.
The primary judgment criterion is: RA activity in a 2 years period of time, measured by repeated DAS44.
The secondary judgment criteria are:
- Percentage of relapse in 1 and 2 years.
- Radiographic structural progression in 1 and 2 years.
- Cost-effectiveness ratio difference between the 2 strategies in 2 years.
As the expected result, this study is aimed to test the feasibility of a step down strategy on 2 biological agents, Abatacept and Tocilizumab, in RA patients in remission.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Tocilizumab, Abatacept, Decrease Tocilizumab, Abatacept
- Keywords
- Rheumatoid arthritis, Disease activity, Remission, Lowest Effective DOse, Abatacept Tocilizumab, ACR-EULAR 2010
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tocilizumab, AbataceptDrug
Also called Tocilizumab: Roactemra 4-8 mg/kg/month (IV injections) and 162 mg/week (SC injections), Abatacept: Orencia 500-1000 mg/month (IV injections) and 125 mg/week (SC injections)
Tocilizumab: Roactemra 4-8 mg/kg/month and 162 mg/week Abatacept: Orencia 500-1000 mg/month and 125 mg/week
Decrease Tocilizumab, AbataceptDrug
Also called Tocilizumab: Roactemra, Abatacept: Orencia
The decrease pattern is established on 4 consecutive stages :
IV Abatacept (500-1000 mg/month) and Tocilizumab(4-8 mg/kg/month):
Stage 0 : Perfusion /30 days Stage 1 :Perfusion/45 days Stage 2 :Perfusion/60 days Stage 3 :Perfusion/90 days Stage 4 :Stop
SC Abatacept (125 mg/week) and Tocilizumab (162 mg/week):
Stage 0 :Injection/7 days Stage 1 :Injection/10 days Stage 2 :Injection/14 days Stage 3 :Injection/21 days Stage 4 :Stop
- If DAS 28 ≤ 2,6 (remission DAS persistent) on trimestrial visit: transfer to next stage for 3 months before next evaluation.
- If DAS 28 > 2,6 et ≤ 3,2 (weak activity) : maintain ongoing stage
- If DAS 28 > 3,2 : return to previous stage, (relapse according to European expert consensus)
In the case of relapse while the patient is in stage 0, the therapy modification is left to the investigator's free will, but the patient will be followed till the end of the study.
| Study group | Role | What they receive |
|---|---|---|
| Maintenance Tocilizumab, Abatacept | Active comparator | No modification in biotherapy dose and administration frequency Receives: Drug: Tocilizumab, Abatacept |
| Decrease Tocilizumab, Abatacept | Experimental | Progressive decrease by predetermined pattern. Progressive injection interval increase (by stage) Receives: Drug: Decrease Tocilizumab, Abatacept |
What is being measured
The primary outcome is the main question the study is designed to answer.
RA activity in a 2 years period of time, measured by repeated DAS44
The primary judgment criterion is: RA activity in a 2 years period of time, measured by repeated DAS44.
Measured: Trimestrial visit (-5 days/ + 35 days)
Secondary outcomes (1)
Radiographic structural progression evaluation and cost-efficiency measure
RA relapse percentage in 1 and 2 years. Radiographic structural progression evaluation by annual radiography.(Sharp score) Cost- efficiency ratio difference between the 2 strategies of maintenance and decrease.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2012 (estimated)
- Study startApr 2012
- Primary completion8 Nov 2019
- Study completion8 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 Assistance Publique - Hôpitaux de ParisThe 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
- 232 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France
- Responsible party
- Sponsor
- Investigators
- Bruno FAUTREL, Pr, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01557374
- Sponsor's protocol ID
- AOM 11061
- Acronym
- TOLEDO
- Status last verified
- Aug 2020
- First submitted
- 16 Mar 2012
- Last updated
- 26 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Kedra J, Dieude P, Giboin C, Marotte H, Salliot C, Schaeverbeke T, Perdriger A, Soubrier M, Morel J, Constantin A, Dernis E, Royant V, Salmon JH, Pham T, Gottenberg JE, Pertuiset E, Dougados M, Devauchelle-Pensec V, Gaudin P, Cormier G, Goupille P, Mariette X, Berenbaum F, Alcaix D, Rouidi SA, Berthelot JM, Monnier A, Piroth C, Liote F, Goeb V, Gaujoux-Viala C, Chary-Valckenaere I, Hajage D, Tubach F, Fautrel B; CRI-IMIDIATE clinical research network. Towards the Lowest Efficacious Dose: Results From a Multicenter Noninferiority Randomized Open-Label Controlled Trial Assessing Tocilizumab or Abatacept Injection Spacing in Rheumatoid Arthritis in Remission. Arthritis Rheumatol. 2024 Apr;76(4):541-552. doi: 10.1002/art.42752. Epub 2024 Jan 25.
PubMed 37942714
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tapering Abatacept or Tocilizumab in Rheumatoid Arthritis in Remission. An Evaluation of Disease Activity, Relapse Risk, Structural Progression and the Economic Impact of a Tapering Strategy
- ClinicalTrials.gov ID
- NCT01557374
- Acronym / sponsor ID
- TOLEDO / AOM 11061
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid arthritis, Disease activity, Remission, Lowest Effective DOse, Abatacept Tocilizumab, ACR-EULAR 2010
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 232 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Ministry of Health, France
- Study start
- Apr 2012 (actual)
- Primary completion
- 8 Nov 2019 (actual)
- Study completion
- 8 Nov 2019 (actual)
- First posted
- 19 Mar 2012 (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.
Ever since the biotherapy agents have entered the market, the recommended therapeutic objective in Rheumatoid arthritis, has been remission. Once obtained, it is advised to try to reduce or cease these biotherapy agents, for which, their efficacy is counterbalanced to their tolerance in the medium and long term as well as their high price. Nevertheless, we do not dispose considerable data on the risks of relapse or structural progression during such a step down strategy. A few studies on anti-TNF agents have shown the possibility of such therapy reduction. A national study, " STRASS ", coordinated by Bruno FAUTREL, has evaluated the possibility of spacing or even stopping the injections of anti-TNF(s). To date, no data concerning Abatacept or Tocilizumab has been published.
As the expected result, this study is aimed to test the feasibility of a step down strategy on 2 biological agents, Abatacept and Tocilizumab, in RA patients in remission.
Detailed description
Ever since the biotherapy agents have entered the market, the recommended therapeutic objective in Rheumatoid arthritis, has been remission. Once obtained, it is advised to try to reduce or cease these biotherapy agents, for which, their efficacy is counterbalanced to their tolerance in the medium and long term as well as their high price.
Nevertheless, we do not dispose considerable data on the risks of relapse or structural progression during such a step down strategy. A few studies on anti-TNF agents have shown the possibility of such therapy reduction. A national study, " STRASS ", coordinated by Bruno FAUTREL, has evaluated the possibility of spacing then stopping the injections of anti-TNF(s). To date, no data concerning Abatacept or Tocilizumab has been published.
This is a Non inferiority, prospective, randomized, controlled study with PROBE (Prospective Randomized, Open Blinded Evaluation) evaluating method.
The objectives of this study are:
- For patients with Rheumatoid Arthritis (RA) in remission under Abatacept or Tocilizumab, to evaluate in terms of disease activity within a 2 years period, the impact of a progressive decreasing biotherapy strategy (by progressively spacing the injections) in comparison with usual treatment (maintaining the usual dose and injection frequency of the biotherapeutic agent).
- To evaluate the impact of such decreasing strategy in terms of RA relapses and structural progression in 1 and 2 years.
- To determine the cost-effectiveness ratio of decreasing in comparison with maintaining the biological treatments.
Inclusion criteria:
Patients with RA, defined by ACR-EULAR 2010 criteria:
- Treated for at least 1 year with Abatacept or Tocilizumab with market authorized doses*, and possibly with a DMARD and ≤ 5 mg per day of corticoids.
- In remission for at least 6 months according to ACR/ EULAR 2010 remission criteria or a DAS 28 ≤ 2.6**
Patients are divided into 2 groups:
- Maintaining strategy: to maintain the biological treatment and possibly the associated DMARD and corticoids.
- Decreasing strategy: to decrease progressively the biological agent via progressively increasing the injection intervals, following a predetermined pattern, established according to the RA activity level, during each trimestrial visit.
The primary judgment criterion is: RA activity in a 2 years period of time, measured by repeated DAS44.
The secondary judgment criteria are:
- Percentage of relapse in 1 and 2 years.
- Radiographic structural progression in 1 and 2 years.
- Cost-effectiveness ratio difference between the 2 strategies in 2 years.
As the expected result, this study is aimed to test the feasibility of a step down strategy on 2 biological agents, Abatacept and Tocilizumab, in RA patients in remission.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Maintenance Tocilizumab, Abatacept | Active comparator | Drug: Tocilizumab, AbataceptNo modification in biotherapy dose and administration frequency |
| Decrease Tocilizumab, Abatacept | Experimental | Drug: Decrease Tocilizumab, AbataceptProgressive decrease by predetermined pattern. Progressive injection interval increase (by stage) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients of at least 18 years old.
- Patients with RA, defined by ACR-EULAR 2010 criteria
- Treated for at least 1 year with Abatacept or Tocilizumab with market authorized doses*, and possibly with a DMARD and ≤ 5 mg per day of corticoids.
- In remission since at least 6 months according to ACR/ EULAR 2010 remission criteria or a DAS 28 ≤ 2.6**
- Without destructive structural progression during the previous year on the hand and feet x-rays (judged by the reference rheumatologist)
Key exclusion criteria (6 listed)
- Already included in another treatment evaluation trial for the same pathology.
- Surgical intervention programmed for in the next 24 months to come.
- Pregnancy or it's anticipation in the next 24 months to come.
- Non comprehension of French language.
- Non affiliation to social security.
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 |
|---|---|---|
| Tocilizumab, AbataceptAlso: Tocilizumab: Roactemra 4-8 mg/kg/month (IV injections) and 162 mg/week (SC injections), Abatacept: Orencia 500-1000 mg/month (IV injections) and 125 mg/week (SC injections)Tocilizumab: Roactemra 4-8 mg/kg/month and 162 mg/week Abatacept: Orencia 500-1000 mg/month and 125 mg/week | Drug | Maintenance Tocilizumab, Abatacept |
| Decrease Tocilizumab, AbataceptAlso: Tocilizumab: Roactemra, Abatacept: OrenciaThe decrease pattern is established on 4 consecutive stages : IV Abatacept (500-1000 mg/month) and Tocilizumab(4-8 mg/kg/month): Stage 0 : Perfusion /30 days Stage 1 :Perfusion/45 days Stage 2 :Perfusion/60 days Stage 3 :Perfusion/90 days Stage 4 :Stop SC Abatacept (125 mg/week) and Tocilizumab (162 mg/week): Stage 0 :Injection/7 days Stage 1 :Injection/10 days Stage 2 :Injection/14 days Stage 3 :Injection/21 days Stage 4 :Stop * If DAS 28 ≤ 2,6 (remission DAS persistent) on trimestrial visit: transfer to next stage for 3 months before next evaluation. * If DAS 28 > 2,6 et ≤ 3,2 (weak activity) : maintain ongoing stage * If DAS 28 > 3,2 : return to previous stage, (relapse according to European expert consensus) In the case of relapse while the patient is in stage 0, the therapy modification is left to the investigator's free will, but the patient will be followed till the end of the study. | Drug | Decrease Tocilizumab, Abatacept |
Primary outcome
RA activity in a 2 years period of time, measured by repeated DAS44
Time frame: Trimestrial visit (-5 days/ + 35 days)
The primary judgment criterion is: RA activity in a 2 years period of time, measured by repeated DAS44.
1 secondary outcome
Radiographic structural progression evaluation and cost-efficiency measure
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2021.
- Derived from this study: PubMed 37942714Kedra J, Dieude P, Giboin C, Marotte H, Salliot C, Schaeverbeke T, Perdriger A, Soubrier M, Morel J, Constantin A, Dernis E, Royant V, Salmon JH, Pham T, Gottenberg JE, Pertuiset E, Dougados M, Devauchelle-Pensec V, Gaudin P, Cormier G, Goupille P, Mariette X, Berenbaum F, Alcaix D, Rouidi SA, Berthelot JM, Monnier A, Piroth C, Liote F, Goeb V, Gaujoux-Viala C, Chary-Valckenaere I, Hajage D, Tubach F, Fautrel B; CRI-IMIDIATE clinical research network. Towards the Lowest Efficacious Dose: Results From a Multicenter Noninferiority Randomized Open-Label Controlled Trial Assessing Tocilizumab or Abatacept Injection Spacing in Rheumatoid Arthritis in Remission. Arthritis Rheumatol. 2024 Apr;76(4):541-552. doi: 10.1002/art.42752. Epub 2024 Jan 25.
- Individual participant dataSharing planned: Undecided
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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.
Bruno FAUTREL, Pr principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tocilizumab, Abatacept and Decrease Tocilizumab, Abatacept in people with Rheumatoid Arthritis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 9 inclusion and 6 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: finished, as of the sponsor's last update on 26 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
RA activity in a 2 years period of time, measured by repeated DAS44 (time frame: Trimestrial visit (-5 days/ + 35 days)). 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 NCT01557374, which also lists 1 linked publication.
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 26 Jan 2021.