Spondyloarthritis
Conditions
Brief summary
The purpose of this study is to evaluate the effect of treatment withdrawal compared to continued treatment with golimumab (GLM) administered by subcutaneous (SC) injection on the incidence of a flare in non-radiographic axial spondyloarthritis over up to 12 months. The primary hypothesis is that continued treatment with golimumab is superior to treatment withdrawal, based on the percentage of subjects without a flare during up to 12 months of blinded therapy.
Interventions
BIOLOGICALGolimumab
Injections of 50 mg golimumab. At the investigator's discretion, participants with a body weight of more than 100 kg could receive 100 mg injections with golimumab.
BIOLOGICALPlacebo
Injections of matching placebo for golimumab.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
To evaluate the effect of treatment withdrawal compared to continued treatment with golimumab (either every month \[QM\] or every 2 months \[Q2M\]) on the incidence of a flare during up to 12 months in Period 2 (blinded therapy).
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Is not of reproductive potential, or is of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner while receiving trial medication or within 6 months after the last dose of trial medication * Has chronic back pain of ≥3 months duration by history * Has physician-diagnosed active non-radiographic axial spondyloarthritis (nr-axSpA) with disease duration \<= 5 years * Meets one of the following criteria: 1. Has active inflammation on magnetic resonance imaging (MRI) highly suggestive of sacroiliitis associated with spondyloarthropathy and 1 or more of the following spondyloarthritis (SpA) characteristics: * Inflammatory back pain * Arthritis (physician-diagnosed) * Enthesitis (heel) physician-diagnosed (spontaneous pain or tenderness at examination of the site of the insertion of the Achilles tendon or plantar fascia) * Dactylitis (physician-diagnosed) * Psoriasis (physician-diagnosed) * History of physician-diagnosed inflammatory bowel disease (IBD) * History of uveitis confirmed by an ophthalmologist * Good response to nonsteroidal anti-inflammatory drugs (NSAID) * Family history of SpA (presence of ankylosing spondylitis, psoriasis, acute uveitis, reactive arthritis, or IBD) * Elevated C-reactive protein (CRP) * Human leukocyte antigen B27 (HLA-B27)+ gene OR 2. Has a HLA-B27+ gene and 2 or more of the following SpA characteristics: * Inflammatory back pain * Arthritis (physician-diagnosed) * Enthesitis (heel) physician-diagnosed (spontaneous pain or tenderness at examination of the site of the insertion of the Achilles tendon or plantar fascia) * Dactylitis (physician-diagnosed) * Psoriasis (physician-diagnosed) * History of physician-diagnosed inflammatory bowel disease (IBD) * History of uveitis confirmed by an ophthalmologist * Good response to nonsteroidal anti-inflammatory drugs (NSAID) * Family history of SpA (presence of ankylosing spondylitis, psoriasis, acute uveitis, reactive arthritis, or IBD) * Elevated C-reactive protein (CRP) * Has elevated CRP at Screening or evidence of active inflammation in the sacroiliac joints on MRI * Has an Ankylosing Spondylitis Disease Activity Score (ASDAS) \>= 2.1 at Screening * Shows high disease activity at Screening and Baseline of both a Total Back Pain score of ≥4 and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of \>= 4 * Has an acceptable history of NSAID use * Has no history of untreated latent or active tuberculosis (TB) prior to Screening * Has had no recent close contact with a person with active TB or, if there has been such contact, will undergo additional evaluations and receive appropriate treatment for latent TB * Agrees to undergo screening for hepatitis B virus (HBV) and demonstrates negative results for hepatitis B surface antigen (HBsAg) and HBV deoxyribonucleic acid (DNA)
Exclusion criteria
* Has bilateral sacroiliitis Grade 2 or unilateral sacroiliitis Grade 3 or Grade 4 on conventional x-rays * Is a nursing or pregnant female, or intends to become pregnant within 6 months after receiving trial medication * Intends to donate eggs (female participants) or sperm (male participants) while receiving trial medication or within 6 months after trial medication * Has any clinically significant condition or situation that would interfere with the trial evaluations or participation in the trial * Has ever received any cytotoxic drugs, including chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents * Has received any treatment listed below more recently than the indicated off-drug period prior to Screening * • Disease-modifying anti-rheumatic drugs (30 days off drug) * • Live vaccinations (3 months off drug) * • Investigational medications (30 days or 5 half-lives off drug, whichever is longer) * • Bacille Calmette-Guerin (BCG) vaccination (12 months off drug) * Has any systemic inflammatory condition, including psoriatic arthritis, active Lyme disease, systemic lupus erythematosus, infectious arthritis, vasculitis, parvovirus infection, rheumatoid arthritis, active uveitis, or active IBD * Has a history of latent or active granulomatous infection prior to Screening * Had a nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to Screening * Has a history of an infected joint prosthesis, or has received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced * Had a serious infection, has been hospitalized for an infection, or has been treated with IV antibiotics for an infection within 2 months prior to Baseline * Had a history of, or ongoing, chronic or recurrent infectious disease * Is known to be infected with human immunodeficiency virus (HIV) or seropositive for hepatitis C virus (HCV) * Has had a chest x-ray within 2 months prior to Screening that shows an abnormality suggestive of a current active infection or malignancy * Has a history of lymphoproliferative disease * Has had a malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of cervix that has been surgically cured) * Has a history of known demyelinating diseases such as multiple sclerosis or optic neuritis * Has a history of or concurrent congestive heart failure of any grade * Has a transplanted organ (with the exception of a corneal transplant performed \>= 3 months prior to baseline) * Has current signs or symptoms of significant medical illness which could interfere with the trial, or require treatment that might interfere with the trial * Is a user of recreational or illicit drugs or has or had a substance abuse (drug or alcohol) problem within the previous 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Without a Disease Activity Flare During Period 2 | Up to 12 months | Disease flare is defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1 relative to baseline prior to the first dose of double-blind treatment in Period 2. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Flare Who Show a Clinical Response Within 3 Months of Open-Label Golimumab Retreatment | Up to 3 months following start of retreatment | Clinical response is defined as Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score improvement of ≥2.0 or ≥50% improvement within 3 months of the start of retreatment, relative to the mean of the two consecutive BASDAI scores that defined the flare. Sustained clinical response refers to participants who attained clinical response and maintained BASDAI criteria throughout the 3-month retreatment period. Response data was collected throughout Period 2 (12 months) and censored to include only the first 3 months after retreatment for a disease flare. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness \[0 (zero) to 10 (2 or more hours)\]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity. |
| Time to First Disease Flare | Month 3, Month 6, Month 9, and Month 12 | The Kaplan-Meier analysis of time to first flare in Period 2 is represented by the percentage of participants who experienced a disease flare relative to baseline prior to the first dose of double-blind treatment in Period 2. Disease flare is defined as ASDAS at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1. |
| Percentage of Participants Achieving ASAS20 (Assessment in SpondyloArthritis International Society) Response (Double-blind Treatment) | Up to 12 months | ASAS20 is a 20% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥20% from Baseline and an absolute improvement from Baseline of ≥1.0 in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a ≥20% worsening and an absolute worsening of ≥1.0) in the potential remaining domain. Baseline for ASAS20 analysis is defined as the last ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. |
| Percentage of Participants Achieving ASAS20 Response (Open-label Retreatment) | Up to 12 months | ASAS20 is a 20% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥20% from Baseline and an absolute improvement from Baseline of ≥1.0 in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a ≥20% worsening and an absolute worsening of ≥1.0) in the potential remaining domain. Baseline for ASAS20 analysis is defined as the last ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. |
| Percentage of Participants Achieving ASAS40 Response (Double-blind Treatment) | Up to 12 months | ASAS40 is a 40% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥40% from Baseline and an absolute improvement from Baseline of ≥2.0 in at least 3 of 4 domains, and 2) No deterioration from Baseline in the potential remaining domain. Baseline for ASAS40 analysis is defined as the last ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. |
| Percentage of Participants Achieving ASAS40 Response (Open-label Retreatment) | Up to 12 months | ASAS40 is a 40% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥40% from Baseline and an absolute improvement from Baseline of ≥2.0 in at least 3 of 4 domains, and 2) No deterioration from Baseline in the potential remaining domain. Baseline for ASAS40 analysis is defined as the last ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. |
| Percentage of Participants Achieving ASAS Partial Remission (Double-blind Treatment) | Up to 12 months | ASAS partial remission is defined as a score of ≤2 in all 4 ASAS domains. Baseline for this analysis is defined as the ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. |
| Percentage of Participants Who Experienced an Adverse Event (AE) in Period 2 | Up to approximately 15 months | This endpoint evaluated the safety and tolerability of withdrawing from or continuing treatment with golimumab in Period 2. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE. The analysis includes AEs that occurred through 90 days after the last dose of study treatment. |
| Percentage of Participants Who Discontinued Study Treatment Due to an AE in Period 2 | Up to approximately 12 months | This endpoint evaluated the safety and tolerability of withdrawing from or continuing treatment with golimumab in Period 2. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE. |
| Percentage of Participants Achieving ASAS Partial Remission (Open-label Retreatment) | Up to 12 months | ASAS partial remission is defined as a score of ≤2 in all 4 ASAS domains. Baseline for this analysis is defined as the ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. |
| Percentage of Participants Achieving BASDAI50 Response (Double-blind Treatment) | Up to 12 months | BASDAI50 is defined as ≥50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score. Baseline for BASDAI50 analysis is defined as the last BASDAI score prior to the first dose of double-blind treatment in Period 2. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness \[0 (zero) to 10 (2 or more hours)\]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity. |
| Percentage of Participants Achieving BASDAI50 Response (Open-label Retreatment) | Up to 12 months | BASDAI50 is defined as ≥50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score. Baseline for BASDAI50 analysis is defined as the last BASDAI score prior to the first dose of open-label retreatment in Period 2. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness \[0 (zero) to 10 (2 or more hours)\]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity. |
| Percentage of Participants Achieving Inactive Disease Status (Double-Blind Treatment) | Up to 12 months | Inactive disease status is defined as an ASDAS score \<1.3. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity. |
| Percentage of Participants Achieving Inactive Disease Status (Open-label Retreatment) | Up to 12 months | Inactive disease status is defined as an ASDAS score \<1.3. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Withdrawal Regimens) | Up to 12 months | Disease flare is defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1 relative to baseline prior to the first dose of double-blind treatment in Period 2. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity. |
| Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Reduced Treatment Regimen) | Up to 12 months | Disease flare is defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1 relative to baseline prior to the first dose of double-blind treatment in Period 2. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity. |
Countries
Czechia, Germany, Netherlands, Poland, Romania, Russia, Spain, Turkey (Türkiye), Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-Label Run-In Golimumab QM Participants were treated with open-label subcutaneous (SC) injections of 50 mg golimumab once a month (QM) for up to 10 months. Participants with a body weight greater than 100 kg may have received 100 mg injections of golimumab at the discretion of the investigator. | 323 |
| Golimumab QM (Full Treatment Regimen) Participants were treated with double-blinded SC injections of 50 mg golimumab QM for up to 12 months. Participants with a body weight greater than 100 kg who had received 100 mg injections of golimumab in Period 1 continued to receive this dosage for the duration of the study. Participants who experienced a disease flare during double-blinded treatment in Period 2 discontinued blinded treatment and were retreated with open-label golimumab. | 63 |
| Golimumab Q2M (Reduced Treatment Regimen) Participants were treated with double-blinded SC injections of 50 mg golimumab every other month (Q2M) alternating with matching placebo to golimumab every other month for up to 12 months. Participants with a body weight greater than 100 kg who had received 100 mg injections of golimumab in Period 1 continued to receive this dosage for the duration of the study. Participants who experienced a disease flare during double-blinded treatment in Period 2 discontinued blinded treatment and were retreated with open-label golimumab. | 64 |
| Placebo (Treatment Withdrawal Regimen) Participants were treated with double-blinded SC injections of placebo for up to 12 months. Participants who experienced a disease flare during double-blinded treatment in Period 2 discontinued blinded treatment and were retreated with open-label golimumab. | 62 |
| Open-Label Retreatment Participants who experienced a disease flare were treated with open-label SC injections of 50 mg golimumab QM for up to 12 months. Participants with a body weight greater than 100 kg who had received 100 mg injections of golimumab in Period 1 continued to receive this dosage for the duration of the study. | 63 |
| Total | 575 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 1: Run-In | Adverse Event | 4 | 0 | 0 | 0 | 0 |
| Period 1: Run-In | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 |
| Period 1: Run-In | Lack of Qualifying Event | 98 | 0 | 0 | 0 | 0 |
| Period 1: Run-In | Protocol Violation | 5 | 0 | 0 | 0 | 0 |
| Period 1: Run-In | Withdrawal by Subject | 8 | 0 | 0 | 0 | 0 |
| Period 2: Open-Label Retreatment | Withdrawal by Subject | 0 | 0 | 0 | 0 | 5 |
| Period 2: Withdrawal vs Continued Tx | Adverse Event | 0 | 0 | 2 | 0 | 0 |
| Period 2: Withdrawal vs Continued Tx | Did not attain inactive disease in Period 1 | 0 | 0 | 1 | 0 | 0 |
| Period 2: Withdrawal vs Continued Tx | Disease Flare, transitioned to Open-label retreatment | 0 | 10 | 15 | 38 | 0 |
| Period 2: Withdrawal vs Continued Tx | Physician Decision | 0 | 0 | 1 | 0 | 0 |
| Period 2: Withdrawal vs Continued Tx | Withdrawal by Subject | 0 | 0 | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Open-Label Run-In Golimumab QM | Total | Open-Label Retreatment | Placebo (Treatment Withdrawal Regimen) | Golimumab Q2M (Reduced Treatment Regimen) | Golimumab QM (Full Treatment Regimen) |
|---|---|---|---|---|---|---|
| Age, Continuous Period 1: Open-Label Run-In | 32.5 Years STANDARD_DEVIATION 7.2 | 32.5 Years STANDARD_DEVIATION 7.2 | — | — | — | — |
| Age, Continuous Period 2: Open-Label Retreatment | — | 33.4 Years STANDARD_DEVIATION 6.7 | 33.4 Years STANDARD_DEVIATION 6.7 | — | — | — |
| Age, Continuous Period 2: Withdrawal vs Continued Tx | — | 31.7 Years STANDARD_DEVIATION 7.2 | — | 32.9 Years STANDARD_DEVIATION 6.8 | 30.8 Years STANDARD_DEVIATION 6.7 | 31.4 Years STANDARD_DEVIATION 8 |
| C-Reactive Protein (CRP) Category at Enrollment Period 1: Open-Label Run-In ≤ 6 mg/L | 127 Participants | 127 Participants | — | — | — | — |
| C-Reactive Protein (CRP) Category at Enrollment Period 1: Open-Label Run-In > 6 mg/L | 196 Participants | 196 Participants | — | — | — | — |
| C-Reactive Protein (CRP) Category at Enrollment Period 2: Open-Label Retreatment ≤ 6 mg/L | — | 25 Participants | 25 Participants | — | — | — |
| C-Reactive Protein (CRP) Category at Enrollment Period 2: Open-Label Retreatment > 6 mg/L | — | 38 Participants | 38 Participants | — | — | — |
| C-Reactive Protein (CRP) Category at Enrollment Period 2: Withdrawal vs Continued Tx ≤ 6 mg/L | — | 70 Participants | — | 23 Participants | 24 Participants | 23 Participants |
| C-Reactive Protein (CRP) Category at Enrollment Period 2: Withdrawal vs Continued Tx > 6 mg/L | — | 119 Participants | — | 39 Participants | 40 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Period 1: Open-Label Run-In Hispanic or Latino | 2 Participants | 2 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Period 1: Open-Label Run-In Not Hispanic or Latino | 321 Participants | 321 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Period 1: Open-Label Run-In Unknown or Not Reported | 0 Participants | 0 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Period 2: Open-Label Retreatment Hispanic or Latino | — | 0 Participants | 0 Participants | — | — | — |
| Ethnicity (NIH/OMB) Period 2: Open-Label Retreatment Not Hispanic or Latino | — | 63 Participants | 63 Participants | — | — | — |
| Ethnicity (NIH/OMB) Period 2: Open-Label Retreatment Unknown or Not Reported | — | 0 Participants | 0 Participants | — | — | — |
| Ethnicity (NIH/OMB) Period 2: Withdrawal vs Continued Tx Hispanic or Latino | — | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Period 2: Withdrawal vs Continued Tx Not Hispanic or Latino | — | 189 Participants | — | 62 Participants | 64 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Period 2: Withdrawal vs Continued Tx Unknown or Not Reported | — | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 1: Open-Label Run-In American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 1: Open-Label Run-In Asian | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Period 1: Open-Label Run-In Black or African American | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Period 1: Open-Label Run-In More than one race | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Period 1: Open-Label Run-In Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Period 1: Open-Label Run-In Unknown or Not Reported | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Period 1: Open-Label Run-In White | 323 Participants | 323 Participants | — | — | — | — |
| Race (NIH/OMB) Period 2: Open-Label Retreatment American Indian or Alaska Native | — | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Period 2: Open-Label Retreatment Asian | — | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Period 2: Open-Label Retreatment Black or African American | — | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Period 2: Open-Label Retreatment More than one race | — | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Period 2: Open-Label Retreatment Native Hawaiian or Other Pacific Islander | — | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Period 2: Open-Label Retreatment Unknown or Not Reported | — | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Period 2: Open-Label Retreatment White | — | 63 Participants | 63 Participants | — | — | — |
| Race (NIH/OMB) Period 2: Withdrawal vs Continued Tx American Indian or Alaska Native | — | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 2: Withdrawal vs Continued Tx Asian | — | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 2: Withdrawal vs Continued Tx Black or African American | — | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 2: Withdrawal vs Continued Tx More than one race | — | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 2: Withdrawal vs Continued Tx Native Hawaiian or Other Pacific Islander | — | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 2: Withdrawal vs Continued Tx Unknown or Not Reported | — | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Period 2: Withdrawal vs Continued Tx White | — | 189 Participants | — | 62 Participants | 64 Participants | 63 Participants |
| Sex: Female, Male Period 1: Open-Label Run-In Female | 109 Participants | 109 Participants | — | — | — | — |
| Sex: Female, Male Period 1: Open-Label Run-In Male | 214 Participants | 214 Participants | — | — | — | — |
| Sex: Female, Male Period 2: Open-Label Retreatment Female | — | 20 Participants | 20 Participants | — | — | — |
| Sex: Female, Male Period 2: Open-Label Retreatment Male | — | 43 Participants | 43 Participants | — | — | — |
| Sex: Female, Male Period 2: Withdrawal vs Continued Tx Female | — | 56 Participants | — | 16 Participants | 21 Participants | 19 Participants |
| Sex: Female, Male Period 2: Withdrawal vs Continued Tx Male | — | 133 Participants | — | 46 Participants | 43 Participants | 44 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 / 323 | 0 / 63 | 0 / 64 | 0 / 62 | 0 / 63 |
| other Total, other adverse events | 79 / 323 | 13 / 63 | 17 / 64 | 11 / 62 | 11 / 63 |
| serious Total, serious adverse events | 7 / 323 | 1 / 63 | 1 / 64 | 1 / 62 | 0 / 63 |
Outcome results
Primary
Percentage of Participants Without a Disease Activity Flare During Period 2
Disease flare is defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1 relative to baseline prior to the first dose of double-blind treatment in Period 2. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized in Period 2, and received at least one dose of double-blind study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Without a Disease Activity Flare During Period 2 | 84.1 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Without a Disease Activity Flare During Period 2 | 68.3 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Percentage of Participants Without a Disease Activity Flare During Period 2 | 33.9 Percentage of participants |
p-value: <0.00195% CI: [34.1, 63.6]Miettinen and Nurminen
p-value: <0.00195% CI: [17, 49.7]Meittinen and Nurminen
Secondary
Percentage of Participants Achieving ASAS20 (Assessment in SpondyloArthritis International Society) Response (Double-blind Treatment)
ASAS20 is a 20% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥20% from Baseline and an absolute improvement from Baseline of ≥1.0 in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a ≥20% worsening and an absolute worsening of ≥1.0) in the potential remaining domain. Baseline for ASAS20 analysis is defined as the last ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized in Period 2, and received at least one dose of double-blind study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving ASAS20 (Assessment in SpondyloArthritis International Society) Response (Double-blind Treatment) | 9.5 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Achieving ASAS20 (Assessment in SpondyloArthritis International Society) Response (Double-blind Treatment) | 3.2 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Percentage of Participants Achieving ASAS20 (Assessment in SpondyloArthritis International Society) Response (Double-blind Treatment) | 0.0 Percentage of participants |
95% CI: [3.3, 19.4]
95% CI: [-2.8, 10.9]
Secondary
Percentage of Participants Achieving ASAS20 Response (Open-label Retreatment)
ASAS20 is a 20% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥20% from Baseline and an absolute improvement from Baseline of ≥1.0 in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a ≥20% worsening and an absolute worsening of ≥1.0) in the potential remaining domain. Baseline for ASAS20 analysis is defined as the last ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized to the reduced-treatment regimen or placebo in Period 2, received at least one dose of double-blind study intervention, and experienced a disease flare during Period 2. Per protocol, participants randomized to the Full Treatment Regimen were not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving ASAS20 Response (Open-label Retreatment) | 94.3 Percentage of participants |
Secondary
Percentage of Participants Achieving ASAS40 Response (Double-blind Treatment)
ASAS40 is a 40% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥40% from Baseline and an absolute improvement from Baseline of ≥2.0 in at least 3 of 4 domains, and 2) No deterioration from Baseline in the potential remaining domain. Baseline for ASAS40 analysis is defined as the last ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized in Period 2, and received at least one dose of double-blind study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving ASAS40 Response (Double-blind Treatment) | 0 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Achieving ASAS40 Response (Double-blind Treatment) | 0 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Percentage of Participants Achieving ASAS40 Response (Double-blind Treatment) | 0 Percentage of participants |
95% CI: [-5.9, 5.8]
95% CI: [-5.9, 5.8]
Secondary
Percentage of Participants Achieving ASAS40 Response (Open-label Retreatment)
ASAS40 is a 40% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥40% from Baseline and an absolute improvement from Baseline of ≥2.0 in at least 3 of 4 domains, and 2) No deterioration from Baseline in the potential remaining domain. Baseline for ASAS40 analysis is defined as the last ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized to the reduced-treatment regimen or placebo in Period 2, received at least one dose of double-blind study intervention, and experienced a disease flare during Period 2. Per protocol, participants randomized to the Full Treatment Regimen were not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving ASAS40 Response (Open-label Retreatment) | 90.6 Percentage of participants |
Secondary
Percentage of Participants Achieving ASAS Partial Remission (Double-blind Treatment)
ASAS partial remission is defined as a score of ≤2 in all 4 ASAS domains. Baseline for this analysis is defined as the ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized in Period 2, and received at least one dose of double-blind study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving ASAS Partial Remission (Double-blind Treatment) | 85.7 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Achieving ASAS Partial Remission (Double-blind Treatment) | 85.7 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Percentage of Participants Achieving ASAS Partial Remission (Double-blind Treatment) | 71.0 Percentage of participants |
95% CI: [0.2, 29]
95% CI: [0.2, 29.1]
Secondary
Percentage of Participants Achieving ASAS Partial Remission (Open-label Retreatment)
ASAS partial remission is defined as a score of ≤2 in all 4 ASAS domains. Baseline for this analysis is defined as the ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized to the reduced-treatment regimen or placebo in Period 2, received at least one dose of double-blind study intervention, and experienced a disease flare during Period 2. Per protocol, participants randomized to the Full Treatment Regimen were not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving ASAS Partial Remission (Open-label Retreatment) | 92.5 Percentage of participants |
Secondary
Percentage of Participants Achieving BASDAI50 Response (Double-blind Treatment)
BASDAI50 is defined as ≥50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score. Baseline for BASDAI50 analysis is defined as the last BASDAI score prior to the first dose of double-blind treatment in Period 2. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness \[0 (zero) to 10 (2 or more hours)\]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized in Period 2, and received at least one dose of double-blind study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving BASDAI50 Response (Double-blind Treatment) | 49.2 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Achieving BASDAI50 Response (Double-blind Treatment) | 30.2 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Percentage of Participants Achieving BASDAI50 Response (Double-blind Treatment) | 24.2 Percentage of participants |
95% CI: [8.5, 40.3]
95% CI: [-9.9, 21.3]
Secondary
Percentage of Participants Achieving BASDAI50 Response (Open-label Retreatment)
BASDAI50 is defined as ≥50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score. Baseline for BASDAI50 analysis is defined as the last BASDAI score prior to the first dose of open-label retreatment in Period 2. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness \[0 (zero) to 10 (2 or more hours)\]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized to the reduced-treatment regimen or placebo in Period 2, received at least one dose of double-blind study intervention, and experienced a disease flare during Period 2. Per protocol, participants randomized to the Full Treatment Regimen were not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving BASDAI50 Response (Open-label Retreatment) | 98.1 Percentage of participants |
Secondary
Percentage of Participants Achieving Inactive Disease Status (Double-Blind Treatment)
Inactive disease status is defined as an ASDAS score \<1.3. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized in Period 2, and received at least one dose of double-blind study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving Inactive Disease Status (Double-Blind Treatment) | 85.7 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Achieving Inactive Disease Status (Double-Blind Treatment) | 84.1 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Percentage of Participants Achieving Inactive Disease Status (Double-Blind Treatment) | 61.3 Percentage of participants |
95% CI: [9.1, 39]
95% CI: [7.3, 37.7]
Secondary
Percentage of Participants Achieving Inactive Disease Status (Open-label Retreatment)
Inactive disease status is defined as an ASDAS score \<1.3. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized to the reduced-treatment regimen or placebo in Period 2, received at least one dose of double-blind study intervention, and experienced a disease flare during Period 2. Per protocol, participants randomized to the Full Treatment Regimen were not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Achieving Inactive Disease Status (Open-label Retreatment) | 90.6 Percentage of participants |
Secondary
Percentage of Participants Who Discontinued Study Treatment Due to an AE in Period 2
This endpoint evaluated the safety and tolerability of withdrawing from or continuing treatment with golimumab in Period 2. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE.
Time frame: Up to approximately 12 months
Population: The analysis population consists of all participants who received at least one dose of study intervention in Period 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Who Discontinued Study Treatment Due to an AE in Period 2 | 0.0 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Who Discontinued Study Treatment Due to an AE in Period 2 | 4.7 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Percentage of Participants Who Discontinued Study Treatment Due to an AE in Period 2 | 1.6 Percentage of participants |
| Open-Label Retreatment | Percentage of Participants Who Discontinued Study Treatment Due to an AE in Period 2 | 0.0 Percentage of participants |
Secondary
Percentage of Participants Who Experienced an Adverse Event (AE) in Period 2
This endpoint evaluated the safety and tolerability of withdrawing from or continuing treatment with golimumab in Period 2. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE. The analysis includes AEs that occurred through 90 days after the last dose of study treatment.
Time frame: Up to approximately 15 months
Population: The analysis population consists of all participants who received at least one dose of study intervention in Period 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Who Experienced an Adverse Event (AE) in Period 2 | 46.0 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Who Experienced an Adverse Event (AE) in Period 2 | 46.9 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Percentage of Participants Who Experienced an Adverse Event (AE) in Period 2 | 32.3 Percentage of participants |
| Open-Label Retreatment | Percentage of Participants Who Experienced an Adverse Event (AE) in Period 2 | 41.3 Percentage of participants |
Secondary
Percentage of Participants With a Flare Who Show a Clinical Response Within 3 Months of Open-Label Golimumab Retreatment
Clinical response is defined as Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score improvement of ≥2.0 or ≥50% improvement within 3 months of the start of retreatment, relative to the mean of the two consecutive BASDAI scores that defined the flare. Sustained clinical response refers to participants who attained clinical response and maintained BASDAI criteria throughout the 3-month retreatment period. Response data was collected throughout Period 2 (12 months) and censored to include only the first 3 months after retreatment for a disease flare. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness \[0 (zero) to 10 (2 or more hours)\]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity.
Time frame: Up to 3 months following start of retreatment
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized to the reduced-treatment regimen or placebo in Period 2, received at least one dose of double-blind study intervention, and experienced a disease flare during Period 2. Per protocol, participants randomized to the Full Treatment Regimen were not included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants With a Flare Who Show a Clinical Response Within 3 Months of Open-Label Golimumab Retreatment | Within 1 month of retreatment | 90.6 Percentage of participants |
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants With a Flare Who Show a Clinical Response Within 3 Months of Open-Label Golimumab Retreatment | Within 3 months of retreatment | 96.2 Percentage of participants |
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants With a Flare Who Show a Clinical Response Within 3 Months of Open-Label Golimumab Retreatment | Within 2 months of retreatment | 96.2 Percentage of participants |
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants With a Flare Who Show a Clinical Response Within 3 Months of Open-Label Golimumab Retreatment | Sustained clinical response | 71.7 Percentage of participants |
Secondary
Time to First Disease Flare
The Kaplan-Meier analysis of time to first flare in Period 2 is represented by the percentage of participants who experienced a disease flare relative to baseline prior to the first dose of double-blind treatment in Period 2. Disease flare is defined as ASDAS at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1.
Time frame: Month 3, Month 6, Month 9, and Month 12
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized in Period 2, and received at least one dose of double-blind study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Time to First Disease Flare | Month 12 | 15.9 Percentage of participants |
| Golimumab QM (Full Treatment Regimen) | Time to First Disease Flare | Month 9 | 14.3 Percentage of participants |
| Golimumab QM (Full Treatment Regimen) | Time to First Disease Flare | Month 6 | 14.3 Percentage of participants |
| Golimumab QM (Full Treatment Regimen) | Time to First Disease Flare | Month 3 | 14.3 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Time to First Disease Flare | Month 3 | 7.9 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Time to First Disease Flare | Month 6 | 17.5 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Time to First Disease Flare | Month 9 | 20.6 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Time to First Disease Flare | Month 12 | 23.8 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Time to First Disease Flare | Month 6 | 58.1 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Time to First Disease Flare | Month 3 | 41.9 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Time to First Disease Flare | Month 12 | 61.3 Percentage of participants |
| Placebo (Treatment Withdrawal Regimen) | Time to First Disease Flare | Month 9 | 61.3 Percentage of participants |
Other Pre-specified
Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Reduced Treatment Regimen)
Disease flare is defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1 relative to baseline prior to the first dose of double-blind treatment in Period 2. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized to receive golimumab in Period 2, and received at least one dose of double-blind study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Reduced Treatment Regimen) | 84.1 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Reduced Treatment Regimen) | 68.3 Percentage of participants |
p-value: 0.03795% CI: [0.9, 30.5]Miettinen and Nurminen
Other Pre-specified
Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Withdrawal Regimens)
Disease flare is defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1 relative to baseline prior to the first dose of double-blind treatment in Period 2. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity.
Time frame: Up to 12 months
Population: The analysis population consists of all participants who attained inactive disease in Period 1, were randomized in Period 2, and received at least one dose of double-blind study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Golimumab QM (Full Treatment Regimen) | Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Withdrawal Regimens) | 84.1 Percentage of participants |
| Golimumab Q2M (Reduced Treatment Regimen) | Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Withdrawal Regimens) | 51.2 Percentage of participants |
p-value: <0.00195% CI: [19.2, 44.5]Miettinen and Nurminen