TOward the Lowest Effective DOse of Abatacept or Tocilizumab

NCT ID: NCT01557374

Last Updated: 2021-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 232 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2019-11-08

Brief 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 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:

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Maintenance Tocilizumab, Abatacept

No modification in biotherapy dose and administration frequency

Group Type: ACTIVE_COMPARATOR

Tocilizumab, Abatacept

Intervention Type: DRUG

Tocilizumab: Roactemra 4-8 mg/kg/month and 162 mg/week Abatacept: Orencia 500-1000 mg/month and 125 mg/week

Decrease Tocilizumab, Abatacept

Progressive decrease by predetermined pattern. Progressive injection interval increase (by stage)

Group Type: EXPERIMENTAL

Decrease Tocilizumab, Abatacept

Intervention Type: DRUG

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.

Interventions

Tocilizumab, Abatacept

Tocilizumab: Roactemra 4-8 mg/kg/month and 162 mg/week Abatacept: Orencia 500-1000 mg/month and 125 mg/week

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention 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); Tocilizumab: Roactemra; Abatacept: Orencia

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruno FAUTREL, Pr

Role: PRINCIPAL_INVESTIGATOR

APHP

Locations

CHU Pitié Salpêtrière

Paris, , France

Countries

France

Other Identifiers

AOM 11061

Identifier Type: -

Identifier Source: org_study_id