Rotation or Change of Biotherapy After TNF Blocker Treatment Failure for Axial Spondyloarthritis (ROC-SPA)

Centre Hospitalier Universitaire de Saint Etienne

Status and phase: Completed; Phase 4

Conditions: Axial Spondyloarthritis

Treatments: Drug: Secukinumab; Biological: blood specimen; Drug: TNF blocker

Study type: Interventional

Funder types: Other

Identifiers

NCT03445845

1608185

2017-004700-22 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 300 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 2 patient groups

targeting IL-23/17 axis

Experimental group

Description:

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

Treatment:

Biological: blood specimen

Drug: Secukinumab

TNF blocker

Active Comparator group

Description:

• 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

Treatment:

Drug: TNF blocker

Biological: blood specimen