A Pragmatic Trial of Interleukin-17 Inhibition Versus Janus Kinase Inhibition After Tumor Necrosis Factor-alpha Inhibitor Failure in Axial Spondyloarthritis

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• Axial Spondyloarthritis 201

Keywords

• comparative effectiveness
• axial spondyloarthritis
• secukinumab
• upadacitinib

Study arms

• Experimental
  Secukinumab (IL-17i )

  Drug: Secukinumab (IL-17i )

• Experimental
  Upadacitinib (JAKi)

  Drug: Upadacitinib (JAKi)

Interventions

• DrugSecukinumab (IL-17i )

  Secukinumab is a fully humanized monoclonal antibody targeting interleukin-17A. Secukinumab will be given as a prefilled syringe or autoinjector for subcutaneous administration. Dosing is 150 mg subcutaneously at weeks 0, 1, 2, 3, and 4 followed by 150mg every 4 weeks thereafter for a total of 16 weeks.

• DrugUpadacitinib (JAKi)

  Upadacitinib is an oral selective inhibitor of janus kinase 1 (JAK1). Participants will take upadacitinib 15mg orally once daily for 16 weeks.

Primary outcomes

1. Feasibility as determined by enrollment of ≥60% of eligible patients

   Time frame: end of treatment (week 16)

2. Feasibility as determined by ≥80% retention of randomized participants

   Time frame: end of treatment (week 16)

3. Feasibility as determined by ≥90% completeness of primary clinical data

   Time frame: end of treatment (week 16)

4. Change in the Ankylosing Spondylitis Disease Activity Score (ASDAS) reported as a mean (SD)

   This is a 4 item questionnaire and one lab result (CRP). The first 4 questions are scored from 0-10. The result is a single numerical score, typically ranging from about 0 to 6, with higher scores indicating more active disease.

   Time frame: Baseline, week 16

Secondary outcomes

1. Number of patients showing an improvement of ≥1.1 and ≥2.0 on the ASDAS score

   Time frame: end of treatment (week 16)

2. Percentage of patients showing an improvement of ≥1.1 and ≥2.0 on the ASDAS score

   Time frame: end of treatment (week 16)

3. Number of participants in the different categories of disease activity as assessed by the ASDAS

   The ASDAS categories are: Inactive disease (\<1.3) Low disease activity (1.3-\<2.1) High disease activity (2.1-3.5) Very high disease activity (\>3.5)

   Time frame: end of treatment (week 16)

4. Percentage of participants in the different categories of disease activity as assessed by the ASDAS

   The ASDAS categories are: Inactive disease (\<1.3) Low disease activity (1.3-\<2.1) High disease activity (2.1-3.5) Very high disease activity (\>3.5)

   Time frame: end of treatment (week 16)

5. Number of participants that have an ASDAS score of <2.1 and ≥2.1

   Time frame: end of treatment (week 16)

6. Percentage of participants that have an ASDAS score of <2.1 and ≥2.1

   Time frame: end of treatment (week 16)

7. Change in patient global disease activity measured as a mean (SD)

   Disease activity is measured using a Numerical Rating Scale (NRS) from 0 (no disease) to 10 (very severe disease)

   Time frame: Baseline, week 16

8. Change in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) measured as a mean (SD)

   The BASDAI is a self-administered 6-question instrument covering fatigue, spinal (axial) pain, peripheral joint pain/swelling, localized tenderness (enthesitis), and the severity and duration of morning stiffness. Each question is scored 0-10. The final result is a single numerical score ranging from 0 to 10, with higher scores indicating more active disease

   Time frame: Baseline, Week 16

9. Change in fatigue as assessed by BASDAI Q1 measured as a mean (SD)

   Fatigue will be assessed using Question 1of the BASDAI and this will be scored on a 0-10 numerical rating scale, where 0 = none and 10 = very severe. The outcome will be reported as the mean (SD). A negative change indicates improvement (reduction in fatigue), while a positive change indicates worsening fatigue

   Time frame: Baseline, week 16

10. Change in total back pain as assessed by BASDAI Q2 measured as a mean (SD)

    Total back pain will be assessed using Question 2 of the BASDAI and this will be scored on a 0-10 numerical rating scale, where 0 = none and 10 = very severe. The outcome will be reported as the mean (SD). A negative change indicates improvement (reduction in pain), while a positive change indicates worsening pain

    Time frame: Baseline, week 16

11. Change in mean stiffness severity as assessed by BASDAI Q5 measured as a mean (SD)

    Stiffness severity will be assessed using Question 5 of the BASDAI and this will be scored on a 0-10 numerical rating scale, where 0 = no stiffness and 10 = most severe stiffness. The outcome will be reported as the mean (SD). A negative change indicates improvement (reduction in stiffness)while a positive change indicates worsening stiffness

    Time frame: Baseline, week 16

12. Change in physical functioning as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) measured as a mean (SD)

    The Bath Ankylosing Spondylitis Functional Index (BASFI) is a self-administered 10-item questionnaire. It comprises 8 questions on function specific to axSpA and 2 questions on the patient's ability to cope with everyday life, each scored 0-10 on a visual analog scale. The final BASFI score is the mean of the 10 items, ranging from 0 (good function) to 10 (poor function), with higher scores indicating worse physical function.

    Time frame: Baseline, week 16

13. Number of participants who met the Assessment of SpondyloArthritis International Society 20% response (ASAS20) criteria

    A participant achieves an ASAS20 response if they have: ≥20% improvement and an absolute improvement of ≥1 unit (on a 0-10 scale) in at least 3 of the following 4 domains, with no worsening (≥20% and ≥1 unit) in the remaining domain. The four domains are: Patient global assessment Spinal pain Physical function (measured by BASFI) Inflammation (average of the two BASDAI morning stiffness questions) Higher percentages indicate a greater proportion of patients experienced clinically meaningful improvement.

    Time frame: end of treatment (week 16 )

14. Percentage (%) of participants who met the ASAS20 response criteria

    A participant achieves an ASAS20 response if they have: ≥20% improvement and an absolute improvement of ≥1 unit (on a 0-10 scale) in at least 3 of the following 4 domains, with no worsening (≥20% and ≥1 unit) in the remaining domain. The four domains are: Patient global assessment Spinal pain Physical function (measured by BASFI) Inflammation (average of the two BASDAI morning stiffness questions) Higher percentages indicate a greater proportion of patients experienced clinically meaningful improvement.

    Time frame: end of treatment (week 16)

15. Number of participants who met the Assessment of SpondyloArthritis International Society 40% response (ASAS40) criteria

    A participant achieves an ASAS40 response if they have: ≥40% improvement and an absolute improvement of ≥2 units in at least 3 of the 4 domains, with No worsening in the remaining domain. Higher percentages indicate a greater proportion of patients experienced clinically meaningful improvement.

    Time frame: end of treatment (week 16)

16. Percentage of participants who met the ASAS40 response criteria

    A participant achieves an ASAS40 response if they have: ≥40% improvement and an absolute improvement of ≥2 units in at least 3 of the 4 domains, with No worsening in the remaining domain. Higher percentages indicate a greater proportion of patients experienced clinically meaningful improvement.

    Time frame: end of treatment (week 16)

17. Change in the impact of axSpA on health and functioning as assessed by the ASAS Health Index (ASAS HI) measured as a mean (SD)

    The ASAS Health Index is a self-reported 17-item questionnaire assessing functioning, disability, and overall health in spondyloarthritis. Each item is answered dichotomously and scored 1 (agree) or 0 (do not agree), producing a summed total score ranging from 0 to 17, with higher scores indicating worse health/greater impairment.

    Time frame: Baseline, week 16

18. Number of patients with improvement ≥3 on the ASAS HI score

    Time frame: end of treatment (week 16)

19. Percentage of patients with improvement ≥3 on the ASAS HI score

    Time frame: end of treatment (week 16)

20. Change in peripheral joint inflammation as assessed by the 44 Tender Joint Count (TJC44) measured as a mean(SD)

    Tender Joint Count (TJC44); each of the 44 joints are scored as 0(not tender) or 1(tender) . The total score ranges from 0-44. Higher scored indicate more active peripheral arthritis.

    Time frame: Baseline, week 16

21. Change in peripheral joint inflammation as assessed by the 44 Swollen Joint Count (SJC44) measured as a mean(SD)

    Swollen Joint Count (SJC44): each of the 44 joints are scored as 0(Not swollen) or 1(Swollen). The total score ranges from 0-44. Higher scored indicate more active peripheral arthritis.

    Time frame: Baseline, week 16

22. Change in peripheral joint inflammation assessed by the Disease Activity Index for Psoriatic Arthritis (DAPSA44) measured as a mean (SD)

    The DAPSA44 is calculated as the simple sum of five components: the 44 Tender Joint Count (TJC44, 0-44), the 44 Swollen Joint Count (SJC44, 0-44), the patient's assessment of peripheral pain (0-10 numeric scale, using BASDAI Q3), the patient's global assessment of disease activity (0-10 numeric scale), and C-reactive protein (mg/dL). The result is a single continuous score, with higher scores indicating greater peripheral disease activity

    Time frame: Baseline, week 16

23. Change in severity of enthesitis as assessed by the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) measured as a mean (SD)

    The Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) is an enthesitis index, in which 13 entheseal sites are examined for tenderness and each scored as 0 (no tenderness) or 1 (tenderness present). The total score ranges from 0 to 13, with higher scores indicating greater entheseal involvement.

    Time frame: Baseline, week 16

24. Change in number of digits with active dactylitis as assessed by the Dactylitis Count measured as a mean(SD)

    The simple dactylitis count assesses each of the 20 digits (10 fingers and 10 toes), scoring each as present (1) or absent (0) for dactylitis. The total score ranges from 0 to 20, with higher scores indicating a greater number of involved digits.

    Time frame: Baseline, week 16

25. Number of patients who developed psoriasis after starting treatment

    Time frame: Baseline to week 16

26. Percentage of patients who developed psoriasis after starting treatment

    Time frame: Baseline to week 16

27. Number of patients who had an occurrence of acute anterior uveitis (AAU) episode since starting treatment

    Time frame: Baseline to week 16

28. Percentage of patients who had an occurrence of acute anterior uveitis (AAU) since starting treatment

    Time frame: Baseline to week 16

29. Number of patients who developed Inflammatory Bowel Disease (IBD) during treatment

    Time frame: Baseline to week 16

30. Percentage of patients who developed Inflammatory Bowel Disease (IBD) during treatment

    Time frame: Baseline to week 16

31. Number of patients who had an adverse event by category during treatment

    Adverse event categories include: 1. Blood and lymphatic system disorders 2. Cardiac disorders 3. Ear and labyrinth disorders 4. Endocrine disorders 5. Eye disorders 6. Gastrointestinal disorders 7. General disorders and administration site conditions 8. Hepatobiliary disorders 9. Immune system disorders 10. Infections and infestation 11. Injury, poisoning and procedural complications 12. Lab abnormalities 13. Metabolism and nutrition disorders 14. Musculoskeletal and connective tissue disorders 15. Neoplasms benign, malignant and unspecified (incl cysts and polyps) 16. Nervous system disorders 17. Psychiatric disorders 18. Renal and urinary disorders 19. Reproductive system and breast disorders 20. Respiratory, thoracic and mediastinal disorders 21. Skin and subcutaneous tissue disorders 22. Vascular disorders

    Time frame: Baseline to week 16

32. Percentage of patients who had an adverse event by category during treatment

    Adverse event categories include: 1. Blood and lymphatic system disorders 2. Cardiac disorders 3. Ear and labyrinth disorders 4. Endocrine disorders 5. Eye disorders 6. Gastrointestinal disorders 7. General disorders and administration site conditions 8. Hepatobiliary disorders 9. Immune system disorders 10. Infections and infestation 11. Injury, poisoning and procedural complications 12. Lab abnormalities 13. Metabolism and nutrition disorders 14. Musculoskeletal and connective tissue disorders 15. Neoplasms benign, malignant and unspecified (incl cysts and polyps) 16. Nervous system disorders 17. Psychiatric disorders 18. Renal and urinary disorders 19. Reproductive system and breast disorders 20. Respiratory, thoracic and mediastinal disorders 21. Skin and subcutaneous tissue disorders 22. Vascular disorders

    Time frame: from baseline to week 16

33. Change in Erythrocyte Sedimentation Rate (ESR) measured as a mean(SD)

    Higher values generally indicate greater systemic inflammation.

    Time frame: Baseline, week 16

34. Change in C-reactive Protein (CRP) measured as a mean(SD)

    Higher values generally indicate greater inflammatory activity..

    Time frame: Baseline, week 16

35. Treatment persistence at week 16

    Treatment persistence is defined as a patient who remains on randomized therapy at week 16.

    Time frame: Week 16

36. Treatment persistence at week 52

    Treatment persistence at week 52 is defined as patients who remain on randomized therapy at week 52

    Time frame: End of study (week 52)

Individual participant data

Plan to share: No