Nonradiographic Axial Spondylitis, Ankylosing
Conditions
Keywords
Nonradiographic Axial Spondylitis, Ankylosing, Ustekinumab
Brief summary
The purpose of this study is to assess the efficacy and safety of ustekinumab in adult participants with active nonradiographic axial spondyloarthritis (nr-AxSpA) measured by the reduction in signs and symptoms of nonradiographic axial spondyloarthritis (nr-AxSpA).
Detailed description
This is a phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of ustekinumab in the treatment of participants with active non-radiographic axial spondylo arthritis. Participants will receive either placebo or ustekinumab 45 or 90 milligram (mg). Participants will primarily be assessed for Assessment of Spondylo Arthritis (ASAS) International Society criteria 20 at Week 24. Safety will be monitored throughout the study.
Interventions
DRUGGroup 1: Placebo
Participants will receive placebo SC at Weeks 0, 4, 16, and 20. At Week 24, all participants (except those who early escaped) will crossover to receive ustekinumab 45 or 90 mg SC at Weeks 24 and 28 followed by every 12 weeks up to Week 52. At Week 16, participants in placebo group with \< 10% improvement from baseline in both total back pain and morning stiffness measures at Week 12 and 16 will enter early escape to receive ustekinumab 45 mg or 90 mg at Weeks 16, 20, and 28 followed by every 12 weeks up to Week 52. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and 52 will be re-randomized to receive placebo or ustekinumab every 12 weeks up to Week 88. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or 52 will continue with ustekinumab every 12 weeks up to Week 88.
DRUGGroup 2: Ustekinumab 45 mg
Participants will receive ustekinumab 45 mg subcutaneously at Weeks 0 and 4, followed by every 12 weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and Week 52 will be re-randomized to receive either placebo or ustekinumab 45 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or Week 52 will continue receiving ustekinumab 45 mg every 12 weeks through Week 88.
DRUGGroup 3: Ustekinumab 90 mg
Participants will receive ustekinumab 90 mg subcutaneously at Weeks 0 and 4, followed by every four weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and Week 52 will receive either placebo or ustekinumab 90 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or Week 52 will continue receiving ustekinumab 90 mg every 12 weeks through Week 88.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Participants must be classified as having nonradiographic axial spondyloarthritis (nr-AxSpA) based on 2009 Assessment of SpondyloArthritis International Society (ASAS) criteria * Must have an age at nr-AxSpA onset of \<= 45 years * Must have at screening or active inflammation on magnetic resonance imaging (MRI) as evidenced by the central readers and no radiographic sacroiliitis that fulfills the 1984 modified New York Criteria * Must have symptoms of active disease at screening and at baseline, as evidenced by both a BASDAI score of \>= 4 and a visual analogue scale (VAS) score for total back pain of more than or equal to (\>=) 4, each on a scale of 0 to 10
Exclusion criteria
* Have radiographic sacroiliitis fulfilling the 1984 modified New York Criteria * Have other inflammatory diseases that might confound the evaluations of benefit from the ustekinumab therapy * Have received any systemic immunosuppressives or disease-modifying anti-rheumatic drug (DMARDs) other than methotrexate (MTX), sulfasalazine (SSZ), or hydroxychloroquine (HCQ) within 4 weeks prior to first administration of study agent * Have received epidural, intra-articular, intramuscular (IM), or intravenous (IV) corticosteroids, including adrenocorticotropic hormone during the 4 weeks prior to first administration of study agent * Have received prior biologic therapy other than anti-TNFα * Have received more than 1 prior anti-TNFα agent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Assessment of SpondyloArthritis International Society (ASAS) 20 Response at Week 24 | Week 24 | ASAS 20 defined as improvement of greater than or equal to (\>=) 20 % from baseline and absolute improvement from baseline of 1 on a 0 to 10 centimeter(cm) scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor), total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 to participant's ability to cope with everyday life), Inflammation (0 to 10 cm;0=none,10=very severe); absence of deterioration (\>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in remaining domain. ASAS20 response based on imputed data using treatment failure (consider non-responders at and after treatment failure),early escape rules (consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 | Week 24 | The BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness (2 questions: duration and severity). Each question is an easy to answer 10 centimeter (cm) visual analog scale (VAS), with 0 being none, and 10 being very severe. In order to give each of the 5 symptoms equal weight, the mean of the 2 questions about morning stiffness were added to the total of the remaining 4 scores, and the final BASDAI score (ranging 0-10) is the average of the overall total score. Higher BASDAI score indicates more severe AS symptom. 50% improvement in response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder). |
| Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 | Baseline, Week 24 | The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of ankylosing spondylitis participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10. Higher BASFI score indicates more severe functional limitations of the participant due to AS. Early escape rule was applied (measurement value at Week 20 and Week 24 was set as missing). |
| Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive Protein (CRP) Inactive Disease (<1.3) at Week 24 | Week 24 | ASDAS includes CRP milligram per liter (mg/L); four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale \[NRS\]) included total back pain(TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment(PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121\*total back pain)+ (0.110\*PGA)+ (0.073\*peripheral pain/swelling)+ (0.058\* DMS)+ (0.579\*Ln(CRP+1)). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 representing a duration of =\>2 hours). Inactive disease is defined as an ASDAS score \<1.3. ASDAS (CRP) Inactive Disease is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI (missing responses at post baseline visit imputed as non-responder). |
| Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Baseline, Week 4, 8, 12, 16, 20 and 24 | Change from baseline in hsCRP levels was reported. hsCRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. Early escape rule was applied (measurement value at Week 20 and Week 24 was set as missing). Here 'n' signifies the number of participants who were analyzed at each specified timepoints, for each arm, respectively. |
| Percentage of Participants With ASAS 20 Components at Week 24 | Week 24 | ASAS 20 defined as \>= 20% improvement from baseline in 4 individual components of ASAS20: Patient's global assessment (PGA) of disease activity (0 to 10cm; 0=very well,10=very poor), total back pain(0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean(0 to10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to functional anatomy and 2 relate to participant's ability to cope with life) and Inflammation (0 to 10cm;0=none,10=very severe). |
| Percentage of Participants Who Achieved an ASAS 40 Response at Week 24 | Week 24 | ASAS 40 defined as improvement of \>= 40% from baseline and absolute improvement from baseline of at least 2 on 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor),total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10 cm; 0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder). |
| Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 4, 8, 12, 16 and 20 | ASAS 20 defined as improvement of \>= 20 % from baseline and absolute improvement from baseline of 1 on a 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor), total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 to participant's ability to cope with everyday life), Inflammation (0 to 10 cm;0=none,10=very severe); absence of deterioration (\>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in remaining domain. ASAS20 response based on imputed data using treatment failure (consider non-responders at and after treatment failure),early escape rules (consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder). |
| Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 4, 8, 12, 16, and 20 | The BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness (2 questions: duration and severity). Each question is an easy to answer 10 centimeter (cm) visual analog scale (VAS), with 0 being none, and 10 being very severe. In order to give each of the 5 symptoms equal weight, the mean of the 2 questions about morning stiffness will be added to the total of the remaining 4 scores, and the final BASDAI score (ranging 0-10) is the average of the overall total score. Higher BASDAI score indicates more severe AS symptom. 50% improvement in BASDAI based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non-responders). |
| Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Baseline, Week 4, 8, 12, 16 and 20 | The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10. Higher BASFI score indicates more severe functional limitations of the participant due to AS. Missing data were imputed using early escape rule (measurement value at Week 20 and 24 was set as missing). Here 'n' defined as number of participants who were analyzed at each specified timepoint, for each arm, respectively. |
| Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 4, 8, 12, 16, and 20 | ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale \[NRS\]) included total back pain(TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment(PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121\*total back pain)+ (0.110\*PGA)+ (0.073\*peripheral pain/swelling)+ (0.058\* DMS)+ (0.579\*Ln(CRP+1)). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 representing a duration of =\>2 hours). Inactive disease is defined as an ASDAS score \<1.3. ASDAS (CRP) Inactive Disease is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI (missing responses at post baseline visit imputed as non-responder). |
| Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 4, 8, 12, 16 and 20 | ASAS 40 defined as improvement of \>= 40% from baseline and absolute improvement from baseline of at least 2 on 0 to10cm scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 response based on imputed data using treatment failure (consider non-responders at and after treatment failure), early escape rules(consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder). |
Countries
Argentina, Australia, Belgium, Czechia, France, Germany, Hungary, Mexico, Poland, Russia, South Korea, Taiwan, Ukraine, United Kingdom
Participant flow
Pre-assignment details
A total of 356 participants were randomized and received treatment (116 participants to placebo, 118 participants to ustekinumab 45 milligram \[mg\], and 122 participants to ustekinumab 90 mg).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo subcutaneous (SC) at Week 0,4,16 and 20. At Week 16, participants in placebo group who qualified for early escape (EE) criteria (with \<10 % improvement from baseline in both total back pain and morning stiffness measures at Week 12 and 16) re-randomized to receive ustekinumab 45mg or 90mg at Week 16,20,28 followed by every 12 Weeks (q12w) through Week 52. Participants received placebo SC at Week 24 to maintain blind. At Week 24, remaining participants in placebo group who did not meet EE criteria, re-randomized to receive ustekinumab 45mg or 90mg at Week 24, 28 followed by q12w through Week 52. At Week 52, participants who achieved inactive disease ASDAS \[ESR\]\<1.3 at Week 40, 52 underwent re-randomization to either ustekinumab or placebo. Participants who did not achieve inactive disease either at Week 40 or 52 received previously assigned ustekinumab dose at scheduled visits. Last dose was scheduled for Week 88 and last study visit for Week 100. | 116 |
| Ustekinumab 45mg Participants received ustekinumab 45 mg SC at Weeks 0 and 4, followed by every 12 weeks through Week 52. At Weeks 20 and 24, participants received placebo subcutaneously to maintain the blind. At Week 52, all participants who achieved inactive disease (Ankylosing Spondylitis Disease Activity Score \[ASDAS\] erythrocyte sedimentation rate \[ESR\] less than \[\<\] 1.3) at both Week 40 and 52 underwent re-randomization to either Ustekinumab or placebo. Participants who did not achieve inactive disease at either Week 40 or 52 received previously assigned ustekinumab dose at their scheduled visits. Last dose was scheduled for Week 88 and last study visit for Week 100. | 118 |
| Ustekinumab 90mg Participants received ustekinumab 90 mg SC at Weeks 0 and 4, followed by every 12 weeks through Week 52. At Weeks 20 and 24, participants received placebo subcutaneously to maintain the blind. At Week 52, all participants who achieved inactive disease (ASDAS ESR\<1.3) at both Week 40 and 52 underwent re-randomization to either Ustekinumab or placebo. Participants who did not achieve inactive disease at either Week 40 or 52 received previously assigned ustekinumab dose at their scheduled visits. Last dose was scheduled for Week 88 and last study visit for Week 100. | 122 |
| Total | 356 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 6 | 6 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 | 2 |
| Overall Study | Other | 29 | 27 | 25 |
| Overall Study | Study Terminated by Sponsor | 77 | 80 | 86 |
| Overall Study | Subject Refused Further Study Treatment | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo | Total | Ustekinumab 90mg | Ustekinumab 45mg |
|---|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 8.75 | 34.3 years STANDARD_DEVIATION 8.73 | 34.9 years STANDARD_DEVIATION 9.06 | 33.9 years STANDARD_DEVIATION 8.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 37 Participants | 13 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 105 Participants | 318 Participants | 109 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants | 35 Participants | 13 Participants | 10 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 36 Participants | 12 Participants | 14 Participants |
| Race/Ethnicity, Customized White Non-Hispanic | 94 Participants | 282 Participants | 97 Participants | 91 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 35 Participants | 13 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 16 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) White | 98 Participants | 301 Participants | 104 Participants | 99 Participants |
| Region of Enrollment ARGENTINA | 2 Participants | 6 Participants | 4 Participants | 0 Participants |
| Region of Enrollment AUSTRALIA | 8 Participants | 22 Participants | 6 Participants | 8 Participants |
| Region of Enrollment BELGIUM | 8 Participants | 27 Participants | 9 Participants | 10 Participants |
| Region of Enrollment CZECH REPUBLIC | 11 Participants | 27 Participants | 8 Participants | 8 Participants |
| Region of Enrollment FRANCE | 6 Participants | 14 Participants | 3 Participants | 5 Participants |
| Region of Enrollment GERMANY | 2 Participants | 18 Participants | 7 Participants | 9 Participants |
| Region of Enrollment HUNGARY | 1 Participants | 10 Participants | 4 Participants | 5 Participants |
| Region of Enrollment MEXICO | 8 Participants | 24 Participants | 7 Participants | 9 Participants |
| Region of Enrollment POLAND | 18 Participants | 45 Participants | 16 Participants | 11 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 18 Participants | 62 Participants | 22 Participants | 22 Participants |
| Region of Enrollment SOUTH KOREA | 6 Participants | 12 Participants | 5 Participants | 1 Participants |
| Region of Enrollment TAIWAN | 6 Participants | 23 Participants | 8 Participants | 9 Participants |
| Region of Enrollment UKRAINE | 18 Participants | 57 Participants | 20 Participants | 19 Participants |
| Region of Enrollment UNITED KINGDOM | 4 Participants | 9 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 52 Participants | 176 Participants | 59 Participants | 65 Participants |
| Sex: Female, Male Male | 64 Participants | 180 Participants | 63 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 116 | 0 / 42 | 0 / 40 | 0 / 118 | 0 / 122 |
| other Total, other adverse events | 19 / 116 | 4 / 42 | 12 / 40 | 27 / 118 | 27 / 122 |
| serious Total, serious adverse events | 2 / 116 | 0 / 42 | 2 / 40 | 2 / 118 | 6 / 122 |
Outcome results
Primary
Percentage of Participants Who Achieved Assessment of SpondyloArthritis International Society (ASAS) 20 Response at Week 24
ASAS 20 defined as improvement of greater than or equal to (\>=) 20 % from baseline and absolute improvement from baseline of 1 on a 0 to 10 centimeter(cm) scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor), total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 to participant's ability to cope with everyday life), Inflammation (0 to 10 cm;0=none,10=very severe); absence of deterioration (\>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in remaining domain. ASAS20 response based on imputed data using treatment failure (consider non-responders at and after treatment failure),early escape rules (consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder).
Time frame: Week 24
Population: Modified Full Analysis Set (MFAS)-participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Assessment of SpondyloArthritis International Society (ASAS) 20 Response at Week 24 | 47.6 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved Assessment of SpondyloArthritis International Society (ASAS) 20 Response at Week 24 | 55.4 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved Assessment of SpondyloArthritis International Society (ASAS) 20 Response at Week 24 | 49.4 Percentage of participants |
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24
The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of ankylosing spondylitis participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10. Higher BASFI score indicates more severe functional limitations of the participant due to AS. Early escape rule was applied (measurement value at Week 20 and Week 24 was set as missing).
Time frame: Baseline, Week 24
Population: MFAS population was included. Participants were analyzed per assigned treatment regardless of actual treatment received. 'N' (number of participants analyzed) signifies number of participants who were evaluable for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 | -2.11 Units on a scale | Standard Deviation 2.371 |
| Ustekinumab 45 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 | -2.28 Units on a scale | Standard Deviation 2.625 |
| Ustekinumab 90 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 | -1.90 Units on a scale | Standard Deviation 2.731 |
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20
The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10. Higher BASFI score indicates more severe functional limitations of the participant due to AS. Missing data were imputed using early escape rule (measurement value at Week 20 and 24 was set as missing). Here 'n' defined as number of participants who were analyzed at each specified timepoint, for each arm, respectively.
Time frame: Baseline, Week 4, 8, 12, 16 and 20
Population: MFAS-participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 16 | -1.05 Units on a scale | Standard Deviation 2.162 |
| Placebo | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 12 | -1.00 Units on a scale | Standard Deviation 2.064 |
| Placebo | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 4 | -0.60 Units on a scale | Standard Deviation 1.582 |
| Placebo | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 8 | -0.82 Units on a scale | Standard Deviation 1.997 |
| Placebo | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 20 | -1.70 Units on a scale | Standard Deviation 2.339 |
| Ustekinumab 45 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 12 | -1.69 Units on a scale | Standard Deviation 2.079 |
| Ustekinumab 45 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 4 | -1.15 Units on a scale | Standard Deviation 1.748 |
| Ustekinumab 45 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 8 | -1.54 Units on a scale | Standard Deviation 2.177 |
| Ustekinumab 45 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 16 | -1.75 Units on a scale | Standard Deviation 2.312 |
| Ustekinumab 45 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 20 | -2.11 Units on a scale | Standard Deviation 2.394 |
| Ustekinumab 90 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 20 | -1.64 Units on a scale | Standard Deviation 2.794 |
| Ustekinumab 90 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 16 | -1.17 Units on a scale | Standard Deviation 2.747 |
| Ustekinumab 90 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 4 | -0.79 Units on a scale | Standard Deviation 1.6 |
| Ustekinumab 90 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 12 | -1.35 Units on a scale | Standard Deviation 2.458 |
| Ustekinumab 90 mg | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 | Change at Week 8 | -1.05 Units on a scale | Standard Deviation 2.095 |
Secondary
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24
Change from baseline in hsCRP levels was reported. hsCRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. Early escape rule was applied (measurement value at Week 20 and Week 24 was set as missing). Here 'n' signifies the number of participants who were analyzed at each specified timepoints, for each arm, respectively.
Time frame: Baseline, Week 4, 8, 12, 16, 20 and 24
Population: MFAS-participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 4 | -0.08 Milligrams per deciliter (mg/dL) | Standard Deviation 1.567 |
| Placebo | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 8 | -0.23 Milligrams per deciliter (mg/dL) | Standard Deviation 1.49 |
| Placebo | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 12 | -0.23 Milligrams per deciliter (mg/dL) | Standard Deviation 1.661 |
| Placebo | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 16 | -0.49 Milligrams per deciliter (mg/dL) | Standard Deviation 1.725 |
| Placebo | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 20 | -0.36 Milligrams per deciliter (mg/dL) | Standard Deviation 1.951 |
| Placebo | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 24 | -0.42 Milligrams per deciliter (mg/dL) | Standard Deviation 2.145 |
| Ustekinumab 45 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 24 | -0.63 Milligrams per deciliter (mg/dL) | Standard Deviation 2.402 |
| Ustekinumab 45 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 4 | -0.10 Milligrams per deciliter (mg/dL) | Standard Deviation 2.574 |
| Ustekinumab 45 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 16 | -0.63 Milligrams per deciliter (mg/dL) | Standard Deviation 2.211 |
| Ustekinumab 45 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 20 | -0.78 Milligrams per deciliter (mg/dL) | Standard Deviation 2.353 |
| Ustekinumab 45 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 8 | -0.53 Milligrams per deciliter (mg/dL) | Standard Deviation 2.084 |
| Ustekinumab 45 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 12 | -0.71 Milligrams per deciliter (mg/dL) | Standard Deviation 2.392 |
| Ustekinumab 90 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 8 | -0.57 Milligrams per deciliter (mg/dL) | Standard Deviation 2.209 |
| Ustekinumab 90 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 12 | -0.61 Milligrams per deciliter (mg/dL) | Standard Deviation 2.534 |
| Ustekinumab 90 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 24 | -0.78 Milligrams per deciliter (mg/dL) | Standard Deviation 2.413 |
| Ustekinumab 90 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 16 | -0.61 Milligrams per deciliter (mg/dL) | Standard Deviation 2.539 |
| Ustekinumab 90 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 4 | -0.39 Milligrams per deciliter (mg/dL) | Standard Deviation 1.601 |
| Ustekinumab 90 mg | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 | Change at Week 20 | -0.76 Milligrams per deciliter (mg/dL) | Standard Deviation 2.383 |
Secondary
Percentage of Participants Who Achieved an ASAS 40 Response at Week 24
ASAS 40 defined as improvement of \>= 40% from baseline and absolute improvement from baseline of at least 2 on 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor),total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10 cm; 0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder).
Time frame: Week 24
Population: MFAS- participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved an ASAS 40 Response at Week 24 | 25.6 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved an ASAS 40 Response at Week 24 | 33.7 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved an ASAS 40 Response at Week 24 | 28.2 Percentage of participants |
Secondary
Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive Protein (CRP) Inactive Disease (<1.3) at Week 24
ASDAS includes CRP milligram per liter (mg/L); four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale \[NRS\]) included total back pain(TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment(PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121\*total back pain)+ (0.110\*PGA)+ (0.073\*peripheral pain/swelling)+ (0.058\* DMS)+ (0.579\*Ln(CRP+1)). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 representing a duration of =\>2 hours). Inactive disease is defined as an ASDAS score \<1.3. ASDAS (CRP) Inactive Disease is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI (missing responses at post baseline visit imputed as non-responder).
Time frame: Week 24
Population: MFAS- participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive Protein (CRP) Inactive Disease (<1.3) at Week 24 | 7.3 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive Protein (CRP) Inactive Disease (<1.3) at Week 24 | 14.5 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive Protein (CRP) Inactive Disease (<1.3) at Week 24 | 12.9 Percentage of participants |
Secondary
Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20
ASAS 20 defined as improvement of \>= 20 % from baseline and absolute improvement from baseline of 1 on a 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor), total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 to participant's ability to cope with everyday life), Inflammation (0 to 10 cm;0=none,10=very severe); absence of deterioration (\>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in remaining domain. ASAS20 response based on imputed data using treatment failure (consider non-responders at and after treatment failure),early escape rules (consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder).
Time frame: Week 4, 8, 12, 16 and 20
Population: MFAS- participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 16 | 40.2 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 12 | 34.1 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 4 | 23.2 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 8 | 31.7 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 20 | 45.1 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 12 | 48.2 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 4 | 26.5 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 8 | 41.0 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 16 | 49.4 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 20 | 59.0 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 20 | 44.7 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 16 | 35.3 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 4 | 32.9 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 12 | 41.2 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 | Week 8 | 36.5 Percentage of participants |
Secondary
Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20
ASAS 40 defined as improvement of \>= 40% from baseline and absolute improvement from baseline of at least 2 on 0 to10cm scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 response based on imputed data using treatment failure (consider non-responders at and after treatment failure), early escape rules(consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder).
Time frame: Week 4, 8, 12, 16 and 20
Population: MFAS- participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 16 | 19.5 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 12 | 17.1 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 4 | 3.7 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 8 | 18.3 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 20 | 24.4 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 12 | 27.7 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 4 | 8.4 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 8 | 19.3 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 16 | 27.7 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 20 | 38.6 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 20 | 32.9 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 16 | 24.7 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 4 | 11.8 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 12 | 24.7 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 | Week 8 | 18.8 Percentage of participants |
Secondary
Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20
The BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness (2 questions: duration and severity). Each question is an easy to answer 10 centimeter (cm) visual analog scale (VAS), with 0 being none, and 10 being very severe. In order to give each of the 5 symptoms equal weight, the mean of the 2 questions about morning stiffness will be added to the total of the remaining 4 scores, and the final BASDAI score (ranging 0-10) is the average of the overall total score. Higher BASDAI score indicates more severe AS symptom. 50% improvement in BASDAI based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non-responders).
Time frame: Week 4, 8, 12, 16, and 20
Population: MFAS- participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 16 | 19.5 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 12 | 18.3 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 4 | 4.9 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 8 | 9.8 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 20 | 15.9 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 12 | 16.9 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 4 | 8.4 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 8 | 15.7 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 16 | 21.7 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 20 | 28.9 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 20 | 32.9 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 16 | 24.7 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 4 | 8.2 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 12 | 28.2 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 | Week 8 | 17.6 Percentage of participants |
Secondary
Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24
The BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness (2 questions: duration and severity). Each question is an easy to answer 10 centimeter (cm) visual analog scale (VAS), with 0 being none, and 10 being very severe. In order to give each of the 5 symptoms equal weight, the mean of the 2 questions about morning stiffness were added to the total of the remaining 4 scores, and the final BASDAI score (ranging 0-10) is the average of the overall total score. Higher BASDAI score indicates more severe AS symptom. 50% improvement in response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder).
Time frame: Week 24
Population: MFAS- participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 | 23.2 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 | 32.5 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 | 25.9 Percentage of participants |
Secondary
Percentage of Participants With ASAS 20 Components at Week 24
ASAS 20 defined as \>= 20% improvement from baseline in 4 individual components of ASAS20: Patient's global assessment (PGA) of disease activity (0 to 10cm; 0=very well,10=very poor), total back pain(0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean(0 to10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to functional anatomy and 2 relate to participant's ability to cope with life) and Inflammation (0 to 10cm;0=none,10=very severe).
Time frame: Week 24
Population: MFAS- participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received. 'N' signifies number of participants who were evaluable for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in PGA score | 64.1 Percentage of participants |
| Placebo | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in total back pain | 62.8 Percentage of participants |
| Placebo | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in BASFI | 53.8 Percentage of participants |
| Placebo | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in inflammation | 64.1 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in inflammation | 66.3 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in PGA score | 61.3 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in BASFI | 57.5 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in total back pain | 60.0 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in inflammation | 65.0 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in total back pain | 60.0 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in BASFI | 56.3 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With ASAS 20 Components at Week 24 | >=20% improvement from baseline in PGA score | 58.8 Percentage of participants |
Secondary
Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20
ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale \[NRS\]) included total back pain(TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment(PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121\*total back pain)+ (0.110\*PGA)+ (0.073\*peripheral pain/swelling)+ (0.058\* DMS)+ (0.579\*Ln(CRP+1)). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 representing a duration of =\>2 hours). Inactive disease is defined as an ASDAS score \<1.3. ASDAS (CRP) Inactive Disease is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI (missing responses at post baseline visit imputed as non-responder).
Time frame: Week 4, 8, 12, 16, and 20
Population: MFAS- participants who were randomized (those participants who would have been able to complete Week 24 at time of study discontinuation) and received at least 1 dose of study drug. Participants were analyzed per assigned treatment regardless of actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 16 | 6.1 Percentage of participants |
| Placebo | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 12 | 4.9 Percentage of participants |
| Placebo | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 4 | 2.4 Percentage of participants |
| Placebo | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 8 | 6.1 Percentage of participants |
| Placebo | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 20 | 3.7 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 12 | 4.8 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 4 | 3.6 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 8 | 7.2 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 16 | 7.2 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 20 | 13.3 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 20 | 15.3 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 16 | 11.8 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 4 | 1.2 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 12 | 10.6 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 | Week 8 | 9.4 Percentage of participants |