Rotation or Change of Biotherapy After TNF Blocker Treatment Failure for Axial Spondyloarthritis

NCT ID: NCT03445845

Last Updated: 2024-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-14
• Study Completion Date: 2024-10-01

Brief Summary

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by inflammatory arthritis and enthesitis involving the spine. AxSpA prevalence is around 0.17% of the French population. Tumor necrosis factor (TNF) was the first target defined in axSpA. Since one third of axSpA patients failed to the first TNF blocker, many axSpA patients received a second biological Disease-Modifying AntiRheumatic Drugs (bDMARDs). Until few months, the only choice was to use a second TNF blocker.Since 2003, pharmaceutical companies investigated efficacy of TNF blockers already used in rheumatoid arthritis. Etanercept is a fusion protein with TNF receptor type II p75 and IgG1 Fc fragment, whereas adalimumab, infliximab, and golimumab are monoclonal antibodies. Certolizumab is a fusion between a fab fragment targeting TNF and a Peg fraction. All demonstrated efficacy versus placebo in a randomized double blinded study

In case of failure to the first TNF blockers, rheumatologists will follow the "Treat-to-Target" principle. This approach already demonstrated its benefit in rheumatoid arthritis or in psoriatic arthritis. This concept was also suggested for axSpA with low levels of evidence and recommendation. So rheumatologist will provide the best treatment in case of failure to the first TNF blockers, which is a daily clinical situation. Since few months, rheumatologists have the choice between targeting IL-23/17 axis compared to a second TNF blocker.

Conditions

Axial Spondyloarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

targeting IL-23/17 axis

The experimental group (targeting IL-23/17 axis) receiving secukinumab in compliance with the marketing authorization regimen: 150 mg per week for 5 weeks, and then every month by subcutaneous injection.

Blood specimen at each visits

Group Type: EXPERIMENTAL

Secukinumab

Intervention Type: DRUG

Secukinumab : 150 mg per week for 5 weeks, and then every month by subcutaneous injection

blood specimen

Intervention Type: BIOLOGICAL

Blood specimen at each visits for measurement of bDMARS blockers concentration and anti-drug antibody concentration

TNF blocker

• The control group receiving a second TNF blocker in compliance with the marketing authorization regimen:

The TNF blocker (originator or biosimilar) will be different to the TNF used before the inclusion and will be chose by the investigator:

• infliximab: 5mg/kg per IV infusion at weeks 0, 2, 6, and then every 6 weeks,
• etanercept: 50mg per week in subcutaneous injection,
• adalimumab: 40mg every other week in subcutaneous injection,
• certolizumab: 400mg every other week 3 times, and then 200mg every other week or 400mg per month in subcutaneous injections,
• golimumab: 50mg every month in subcutaneous injection, in case of overweight (>100kg) an inadequate response, 100mg every month is allow.

Blood specimen at each visits

Group Type: ACTIVE_COMPARATOR

TNF blocker

Intervention Type: DRUG

TNF blocker (originator or biosimilar) :

• infliximab: 5mg/kg per IV infusion at weeks 0, 2, 6, and then every 6 weeks,
• etanercept: 50mg per week in subcutaneous injection,
• adalimumab: 40mg every other week in subcutaneous injection,
• certolizumab: 400mg every other week 3 times, and then 200mg every other week or 400mg per month in subcutaneous injections,
• golimumab: 50mg every month in subcutaneous injection, in case of overweight (>100kg) an inadequate response, 100mg every month is allow.

blood specimen

Intervention Type: BIOLOGICAL

Blood specimen at each visits for measurement of bDMARS blockers concentration and anti-drug antibody concentration

Interventions

Secukinumab

Secukinumab : 150 mg per week for 5 weeks, and then every month by subcutaneous injection

Intervention Type: DRUG

TNF blocker

TNF blocker (originator or biosimilar) :

• infliximab: 5mg/kg per IV infusion at weeks 0, 2, 6, and then every 6 weeks,
• etanercept: 50mg per week in subcutaneous injection,
• adalimumab: 40mg every other week in subcutaneous injection,
• certolizumab: 400mg every other week 3 times, and then 200mg every other week or 400mg per month in subcutaneous injections,
• golimumab: 50mg every month in subcutaneous injection, in case of overweight (>100kg) an inadequate response, 100mg every month is allow.

Intervention Type: DRUG

blood specimen

Blood specimen at each visits for measurement of bDMARS blockers concentration and anti-drug antibody concentration

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Active axSPA with BASDAI>4 or ASDAS>3.5, who need change in TNF blocker treatment
• Aged over 18 years
• Inadequate response after at least 3 months to the 1st TNF blocker
• If non biologic DMARD treatment : stable dose for at least on month before inclusion
• If oral corticosteroids treatment : stable dose for at least on month before inclusion
• If NSAIDs treatment : stable dose for at least on month before inclusion
• Ability to complete questionnaires
• Social security affiliation
• Informed written consent given

Exclusion Criteria

• Any contra-indication to TNF blocker and/or secukinumab
• Inflammatory bowel diseases
• Existing pregnancy, lactation, or intended pregnancy within the next 15 months Active tuberculosis or other severe infections such as sepsis or opportunistic infections
• Active infections, including chronic or localised infections.
• Moderate to severe heart failure (NYHA classes III/IV)
• Impossibility to give informed consent
• Impossibility to be followed for 12 months

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

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hubert MAROTTE, MD

Role: STUDY_DIRECTOR

CHU SAINT-ETIENNE

Locations

CHU d'Angers

Angers, , France

CHRU Besançon

Besançon, , France

APHP- Hôpital Avicenne

Bobigny, , France

CHU Bordeaux

Bordeau, , France

CHRU Brest

Brest, , France

CHU Clermont-Ferrand

Clermont-Ferrand, , France

CHU de Grenoble Alpes

Grenoble, , France

CHD Vendée

La Roche-sur-Yon, , France

CH Le Mans

Le Mans, , France

CHRU Lille

Lille, , France

Hôpital Saint-Philibert

Lomme, , France

CH Lyon SUD

Lyon, , France

Hôpital Edouard Herriot

Lyon, , France

CHRU Montpellier

Montpellier, , France

CHU Montpellier - 2 - Unité Clinique thérapeutique des Maladies Ostéo-Articulaires

Montpellier, , France

CHU Nancy

Nancy, , France

CHU de Nantes

Nantes, , France

CHU de Nice

Nice, , France

CHR d'Orléans

Orléans, , France

APHP - Hôpital Ambroise Paré

Paris, , France

APHP - Hôpital Bichat

Paris, , France

APHP - Hôpital Cochin

Paris, , France

APHP - Hôpital Henri Mondor

Paris, , France

APHP - Hôpital Lariboisière

Paris, , France

APHP - Hôpital Pitié-Salpétrière

Paris, , France

APHP - Hôpital Saint-Antoine

Paris, , France

APHP - Kremlin-Bicêtre

Paris, , France

CHU de Poitiers

Poitiers, , France

CHU Reims

Reims, , France

CHU de Rouen

Rouen, , France

CHU Saint-Etienne

Saint-Etienne, , France

CHU STRASBOURG - Hautepierre

Strasbourg, , France

CHU Toulouse

Toulouse, , France

CHRU Tours

Tours, , France

CH Princesse de Grace

Monaco, , Monaco

Countries

France; Monaco

References

Dalix E, Marcelli C, Bejan-Angoulvant T, Finckh A, Rancon F, Akrour M, De Araujo L, Presles E, Marotte H; ROC-SpA study group. Rotation or change of biotherapy after TNF blocker treatment failure for axial spondyloarthritis: the ROC-SpA study, a randomised controlled study protocol. BMJ Open. 2024 Sep 10;14(9):e087872. doi: 10.1136/bmjopen-2024-087872.

Reference Type: DERIVED

PMID: 39260856 (View on PubMed)

Other Identifiers

2017-004700-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1608185

Identifier Type: -

Identifier Source: org_study_id