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

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.

Study Overview

• Status: Completed
• Conditions: Axial Spondyloarthritis
• Intervention / Treatment: Drug: Secukinumab; Biological: blood specimen; Drug: TNF blocker

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU d'Angers
  • Besançon, France
    • CHRU Besançon
  • Bobigny, France
    • APHP- Hôpital Avicenne
  • Bordeau, France
    • Chu Bordeaux
  • Brest, France
    • CHRU Brest
  • Clermont-Ferrand, France
    • Chu Clermont-Ferrand
  • Grenoble, France
    • CHU de Grenoble Alpes
  • La Roche-sur-Yon, France
    • CHD Vendee
  • Le Mans, France
    • CH Le mans
  • Lille, France
    • CHRU Lille
  • Lomme, France
    • Hôpital Saint-Philibert
  • Lyon, France
    • Hopital Edouard Herriot
  • Lyon, France
    • CH Lyon Sud
  • Montpellier, France
    • CHRU Montpellier
  • Montpellier, France
    • CHU Montpellier - 2 - Unité Clinique thérapeutique des Maladies Ostéo-Articulaires
  • Nancy, France
    • CHU Nancy
  • Nantes, France
    • CHU de Nantes
  • Nice, France
    • CHU de Nice
  • Orléans, France
    • CHR d'Orléans
  • Paris, France
    • APHP - Hopital Cochin
  • Paris, France
    • APHP - Hopital Bichat
  • Paris, France
    • APHP - Hôpital Saint-Antoine
  • Paris, France
    • APHP - Kremlin-Bicêtre
  • Paris, France
    • APHP - Hopital Ambroise Pare
  • Paris, France
    • APHP - Hôpital Henri Mondor
  • Paris, France
    • APHP - Hôpital Lariboisière
  • Paris, France
    • APHP - hôpital Pitié-Salpêtrière
  • Poitiers, France
    • Chu de Poitiers
  • Reims, France
    • Chu Reims
  • Rouen, France
    • CHU de ROUEN
  • Saint-Étienne, France, 42055
    • CHU Saint-Etienne
  • Strasbourg, France, 67200
    • CHU Strasbourg - Hautepierre
  • Toulouse, France
    • CHU Toulouse
  • Tours, France
    • CHRU Tours
• Monaco
  • Monaco, Monaco
    • CH Princesse de Grace

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Secukinumab; Secukinumab : 150 mg per week for 5 weeks, and then every month by subcutaneous injection; Biological: blood specimen; Blood specimen at each visits for measurement of bDMARS blockers concentration and anti-drug antibody concentration
Active Comparator: 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	Biological: blood specimen; Blood specimen at each visits for measurement of bDMARS blockers concentration and anti-drug antibody concentration; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of axSpA patients with a clinical response Assessments in Ankylosing Spondylitis International Society 40 (ASAS 40) at week 24	ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."; Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."; Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible."; Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain	24 weks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of axSpA patients with a clinical response ASAS 40 at week 12	ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."; Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."; Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible."; Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain	12 weeks
Proportion of axSpA patients with a clinical response ASAS 40 at week 52	ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."; Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."; Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible."; Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain	52 weeks
Proportion of axSpA patients with a clinical response ASAS 20 at week 12	ASAS 20 is defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."; Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."; Function : BASFI average of 10 questions regarding measured by numerical rating scale with extremes labelled "easy" and "impossible."; Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening in a similar amount in the fourth domain	52 weeks
Proportion of axSpA patients with a clinical response ASAS 20 at week 24	ASAS 20 is defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."; Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."; Function : BASFI average of 10 questions regarding measured by numerical rating scale with extremes labelled "easy" and "impossible."; Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening in a similar amount in the fourth domain	24 weeks
Proportion of axSpA patients with a clinical response ASAS20 at week 52	ASAS 20 is defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."; Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."; Function : BASFI average of 10 questions regarding measured by numerical rating scale with extremes labelled "easy" and "impossible."; Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening in a similar amount in the fourth domain	52 weeks
Proportion of axSpA patients with a partial remission rate at week 12	Partial remission is defined by values lower than 2/10 in each 4 domains: Patient global assessment measured on a numerical rating scale with extremes labelled "none" and "severe."; Pain assessment represented by the average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."; Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by numerical rating scale with extremes labelled "easy" and "impossible."; Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours."	12 weeks
Proportion of axSpA patients with a partial remission rate at week 24	Partial remission is defined by values lower than 2/10 in each 4 domains: Patient global assessment measured on a numerical rating scale with extremes labelled "none" and "severe."; Pain assessment represented by the average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."; Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by numerical rating scale with extremes labelled "easy" and "impossible."; Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours."	24 weeks
Proportion of axSpA patients with a partial remission rate at week 52	Partial remission is defined by values lower than 2/10 in each 4 domains: Patient global assessment measured on a numerical rating scale with extremes labelled "none" and "severe."; Pain assessment represented by the average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."; Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by numerical rating scale with extremes labelled "easy" and "impossible."; Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours."	52 weeks
Proportion of axSpA patients with a ASDAS major improvement at week 12	ASDAS major improvement was defined by a variation of ASDAS-CRP≥2	12 weeks
Proportion of axSpA patients with a ASDAS major improvement at week 24	ASDAS major improvement was defined by a variation of ASDAS-CRP≥2	24 weeks
Proportion of axSpA patients with a ASDAS major improvement at week 52	ASDAS major improvement was defined by a variation of ASDAS-CRP≥2	52 weeks
Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 12	Patient with the same bDAMRs treatment at inclusion and week 12	12 weeks
Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 24	Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 24	24 weeks
Proportion of axSpA patients with bDMARDs treatment at week 52	Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 52	52 weeks
Number of adverse events	Number of adverse events	52 weeks
Correlation between concentration of antibodies to bDMARS blockers and clinical response according to treatment	Concentration of antibodies to bDMARS blockers is measured by Enzyme Linked ImmunoSorbent Assay (ELISA) low disease activity is defined by BASDAI <4 and ASDAS <2.1	From baseline to 52 weeks
Correlation between concentration of anti-drug antibodies and clinical response according to treatment	Concentration of anti-drug antibodies is measured by Enzyme Linked ImmunoSorbent Assay (ELISA) low disease activity is defined by BASDAI <4 and ASDAS <2.1	From baseline to 52 weeks

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Ministry of Health, France
• Investigators: Study Director: Hubert MAROTTE, MD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2018
• Primary Completion (Actual): September 21, 2024
• Study Completion (Actual): October 1, 2024

Study Registration Dates

• First Submitted: February 20, 2018
• First Submitted That Met QC Criteria: February 20, 2018
• First Posted (Actual): February 26, 2018

Study Record Updates

• Last Update Posted (Actual): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 15, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: TNF blocker; change of biotherapy
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Infections; Bone Diseases, Infectious; Spinal Diseases; Spondylarthropathies; Ankylosis; Axial Spondyloarthritis; Spondylitis; Spondylarthritis; Anti-Inflammatory Agents; Tumor Necrosis Factor Inhibitors
• Other Study ID Numbers: 1608185; 2017-004700-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No