TOward the Lowest Effective DOse of Abatacept or Tocilizumab (TOLEDO)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01557374
First received: March 16, 2012
Last updated: June 20, 2016
Last verified: June 2016
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Tocilizumab, Abatacept
Drug: Decrease Tocilizumab, Abatacept
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • RA activity in a 2 years period of time, measured by repeated DAS44 [ Time Frame: Trimestrial visit (-5 days/ + 35 days) ] [ Designated as safety issue: No ]
    The primary judgment criterion is: RA activity in a 2 years period of time, measured by repeated DAS44.


Secondary Outcome Measures:
  • Radiographic structural progression evaluation and cost-efficiency measure [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 232
Study Start Date: April 2012
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Maintenance Tocilizumab, Abatacept
No modification in biotherapy dose and administration frequency
Drug: Tocilizumab, Abatacept
Tocilizumab: Roactemra 4-8 mg/kg/month and 162 mg/week Abatacept: Orencia 500-1000 mg/month and 125 mg/week
Other Names:
  • 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)
Experimental: Decrease Tocilizumab, Abatacept
Progressive decrease by predetermined pattern. Progressive injection interval increase (by stage)
Drug: Decrease Tocilizumab, Abatacept

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.

Other Names:
  • Tocilizumab: Roactemra
  • Abatacept: Orencia

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:

  1. Maintaining strategy: to maintain the biological treatment and possibly the associated DMARD and corticoids.
  2. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01557374

Locations
France
CHU Pitié Salpêtrière
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Ministry of Health, France
Investigators
Principal Investigator: Bruno FAUTREL, Pr APHP
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01557374     History of Changes
Other Study ID Numbers: AOM 11061 
Study First Received: March 16, 2012
Last Updated: June 20, 2016
Health Authority: France: Ministry of Health
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Rheumatoid arthritis
Disease activity
Remission
Lowest Effective DOse
Abatacept Tocilizumab
ACR-EULAR 2010

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 25, 2016