Clinical trial NCT03445845: Rotation or Change of Biotherapy After TNF Blocker Treatment Failure for Axial Spondyloarthritis
Official title: Rotation or Change of Biotherapy After TNF Blocker Treatment Failure for Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Axial Spondyloarthritis
Keywords: TNF blocker
change of biotherapy
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2018-02-26
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Proportion of axSpA patients with a clinical response Assessments in Ankylosing Spondylitis International Society 40 (ASAS 40) at week 24
timeFrame: 24 weks
Secondary outcomes:
measure: Proportion of axSpA patients with a clinical response ASAS 40 at week 12
timeFrame: 12 weeks
measure: Proportion of axSpA patients with a clinical response ASAS 40 at week 52
timeFrame: 52 weeks
measure: Proportion of axSpA patients with a clinical response ASAS 20 at week 12
timeFrame: 52 weeks
measure: Proportion of axSpA patients with a clinical response ASAS 20 at week 24
timeFrame: 24 weeks
measure: Proportion of axSpA patients with a clinical response ASAS20 at week 52
timeFrame: 52 weeks
measure: Proportion of axSpA patients with a partial remission rate at week 12
timeFrame: 12 weeks
measure: Proportion of axSpA patients with a partial remission rate at week 24
timeFrame: 24 weeks
measure: Proportion of axSpA patients with a partial remission rate at week 52
timeFrame: 52 weeks
measure: Proportion of axSpA patients with a ASDAS major improvement at week 12
timeFrame: 12 weeks
measure: Proportion of axSpA patients with a ASDAS major improvement at week 24
timeFrame: 24 weeks
measure: Proportion of axSpA patients with a ASDAS major improvement at week 52
timeFrame: 52 weeks
measure: Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 12
timeFrame: 12 weeks
measure: Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 24
timeFrame: 24 weeks
measure: Proportion of axSpA patients with bDMARDs treatment at week 52
timeFrame: 52 weeks
measure: Number of adverse events
timeFrame: 52 weeks
measure: Correlation between concentration of antibodies to bDMARS blockers and clinical response according to treatment
timeFrame: From baseline to 52 weeks
measure: Correlation between concentration of anti-drug antibodies and clinical response according to treatment
timeFrame: From baseline to 52 weeks
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Besançon
country: France
facility: CHRU Besançon
city: Bobigny
country: France
facility: APHP- Hôpital Avicenne
city: Bordeau
country: France
facility: CHU Bordeaux
city: Brest
country: France
facility: CHRU Brest
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Grenoble
country: France
facility: CHU de Grenoble Alpes
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Le Mans
country: France
facility: CH Le Mans
city: Lille
country: France
facility: CHRU Lille
city: Lomme
country: France
facility: Hôpital Saint-Philibert
city: Lyon
country: France
facility: CH Lyon SUD
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Montpellier
country: France
facility: CHRU Montpellier
city: Montpellier
country: France
facility: CHU Montpellier - 2 - Unité Clinique thérapeutique des Maladies Ostéo-Articulaires
city: Nancy
country: France
facility: CHU Nancy
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: CHU de Nice
city: Orléans
country: France
facility: CHR d'Orléans
city: Paris
country: France
facility: APHP - Hôpital Ambroise Paré
city: Paris
country: France
facility: APHP - Hôpital Bichat
city: Paris
country: France
facility: APHP - Hôpital Cochin
city: Paris
country: France
facility: APHP - Hôpital Henri Mondor
city: Paris
country: France
facility: APHP - Hôpital Lariboisière
city: Paris
country: France
facility: APHP - Hôpital Pitié-Salpétrière
city: Paris
country: France
facility: APHP - Hôpital Saint-Antoine
city: Paris
country: France
facility: APHP - Kremlin-Bicêtre
city: Poitiers
country: France
facility: CHU de Poitiers
city: Reims
country: France
facility: CHU Reims
city: Rouen
country: France
facility: CHU de Rouen
city: Saint-Étienne
country: France
facility: CHU Saint-Etienne
city: Strasbourg
country: France
facility: CHU STRASBOURG - Hautepierre
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: CHRU Tours
city: Monaco
country: Monaco
facility: CH Princesse de Grace
Study officials:
affiliation: CHU SAINT-ETIENNE
name: Hubert MAROTTE, MD
role: STUDY_DIRECTOR
References: