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Completed

NCT Number: NCT03445845

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

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.

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Key information

Conditions

Axial Spondyloarthritis Ankylosis Arthritis Bone Diseases Joint Diseases Musculoskeletal Diseases Spinal Diseases Spondylarthritis Spondylarthropathies Spondylitis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

CHU d'Angers, Angers, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

secukinumab

Drug

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

TNF blocker

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

Biological

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

Primary outcomes

  1. Proportion of axSpA patients with a clinical response Assessments in Ankylosing Spondylitis International Society 40 (ASAS 40) at week 24

    Time frame: 24 weks

    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

Secondary outcomes

  1. Proportion of axSpA patients with a clinical response ASAS 40 at week 12

    Time frame: 12 weeks

    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

  2. Proportion of axSpA patients with a clinical response ASAS 40 at week 52

    Time frame: 52 weeks

    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

  3. Proportion of axSpA patients with a clinical response ASAS 20 at week 12

    Time frame: 52 weeks

    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

  4. Proportion of axSpA patients with a clinical response ASAS 20 at week 24

    Time frame: 24 weeks

    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

  5. Proportion of axSpA patients with a clinical response ASAS20 at week 52

    Time frame: 52 weeks

    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

  6. Proportion of axSpA patients with a partial remission rate at week 12

    Time frame: 12 weeks

    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."

  7. Proportion of axSpA patients with a partial remission rate at week 24

    Time frame: 24 weeks

    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."

  8. Proportion of axSpA patients with a partial remission rate at week 52

    Time frame: 52 weeks

    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."

  9. Proportion of axSpA patients with a ASDAS major improvement at week 12

    Time frame: 12 weeks

    ASDAS major improvement was defined by a variation of ASDAS-CRP≥2

  10. Proportion of axSpA patients with a ASDAS major improvement at week 24

    Time frame: 24 weeks

    ASDAS major improvement was defined by a variation of ASDAS-CRP≥2

  11. Proportion of axSpA patients with a ASDAS major improvement at week 52

    Time frame: 52 weeks

    ASDAS major improvement was defined by a variation of ASDAS-CRP≥2

  12. Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 12

    Time frame: 12 weeks

    Patient with the same bDAMRs treatment at inclusion and week 12

  13. Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 24

    Time frame: 24 weeks

    Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 24

  14. Proportion of axSpA patients with bDMARDs treatment at week 52

    Time frame: 52 weeks

    Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 52

  15. Number of adverse events

    Time frame: 52 weeks

    Number of adverse events

  16. Correlation between concentration of antibodies to bDMARS blockers and clinical response according to treatment

    Time frame: From baseline to 52 weeks

    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

  17. Correlation between concentration of anti-drug antibodies and clinical response according to treatment

    Time frame: From baseline to 52 weeks

    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

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Saint Etienne

Other

Collaborators

  • Ministry of Health, France

Registry information

Acronym: ROC-SPA

Important dates

Study start
2018
Primary completion
2024
Study completion
2024
First posted
Feb 26, 2018
Registry last updated
Nov 18, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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