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

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 4

Conditions: Rheumatoid Arthritis

Treatments: Drug: Decrease Tocilizumab, Abatacept; Drug: Tocilizumab, Abatacept

Study type: Interventional

Funder types: Other

Identifiers

NCT01557374

AOM 11061

Details and patient eligibility

About

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.

Full 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.

Enrollment: 232 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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232 participants in 2 patient groups

Maintenance Tocilizumab, Abatacept

Active Comparator group

Description:

No modification in biotherapy dose and administration frequency

Treatment:

Drug: Tocilizumab, Abatacept

Decrease Tocilizumab, Abatacept

Experimental group

Description:

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

Treatment:

Drug: Decrease Tocilizumab, Abatacept