Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis, Golimumab, Methotrexate, Tumor Necrosis Factor-alpha, Immunology
Brief summary
The purpose of this study is to assess the clinical effectiveness and safety of golimumab intravenous (IV) infusions every 12 weeks with or without Methotrexate (MTX), compared with MTX alone, in patients with active rheumatoid arthritis (RA) despite concurrent MTX treatment. In addition, the safety of subcutaneous (SC) golimumab injections following transition from IV golimumab infusions will also be evaluated.
Detailed description
This is a Phase III, double blind (neither investigator nor participant knows the treatment received), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), multicenter, 5-arm (treatment groups) study of golimumab at 2 doses (given with or without MTX over a period of 30 minutes) for at least 48 weeks in patients with active RA despite concurrent MTX therapy. The study consists of a treatment period of golimumab IV infusions (IV Period) which ranges from 48 weeks to approximately 140 weeks, assuming an enrollment period of approximately 92 weeks, and a long-term optional extension period (Extension Study) in which golimumab SC injections will be given for 24 weeks. The end of study will be the time the last participant completes the Week E-40 visit (Extension Study) for safety follow-up assessments. For the IV Period, participants will be randomly assigned to 1 of the 5 treatment groups in a 1:1:1:1:1 ratio (approximately 125 patients per group). At Week 16 and Week 24, joint assessment results will be used to allow participants to enter early escape and dose regimen adjustment, respectively, in a blinded fashion. Treatment will be unblinded after the 48-week database lock and participants will be given the option to participate in the Extension Study and receive SC injections of 50mg golimumab (with or without MTX) every 4 weeks for an additional 24 weeks. Safety will be monitored throughout the study. The entire study duration (IV Period plus Extension Study) for each participant will range from 88 weeks up to 192 weeks, assuming an enrollment period of approximately 92 weeks.
Interventions
DRUGGolimumab
2mg/kg or 4mg/kg will be administered as an IV infusion over 30 minutes
DRUGMethotrexate
Active MTX capsules, filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg MTX tablet, will be administered at the same dose as before the study entry.
DRUGPlacebo
Placebo solution will be administered through IV infusion in Group V and oral placebo capsules (sham MTX) filled with microcrystalline cellulose (Avicel PH 102) will be administered in Group II and IV.
Sponsors
Schering-Plough
Centocor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- Must have a diagnosis of active rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ARA (American Rheumatism Association) with at least 4 swollen and 4 tender joints for at least 3 months prior to screening - Have been treated with and tolerated methotrexate (MTX) at a dose of at least 15 mg per week for at least 3 months prior to screening - Have been on a stable MTX dose of greater than or equal to 15 mg per week and less than or eual to 25 mg per week for at least 4 weeks prior to screening - If using non steroidal anti-inflammatory agents (such as naproxen) or other pain relievers for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent
Exclusion criteria
\- Participants having known hypersensitivity (severe allergy) to human immunoglobulin proteins or other components of golimumab - Having known clinically serious adverse reaction to a biologic anti-TNF agent - Have had history of latent or active granulomatous infection, including tuberculosis, histoplasmosis, or coccidioidomycosis, prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14 | Week 0 to Week 14 | An ACR 50 response is defined as a greater than or equal to 50 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b. Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | Week 0 to Week 24 | ACR 50 response is an improvement of greater than or equal to 50 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity (based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities) and CRP blood test to measure inflammation). |
| Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14 | Week 0 to Week 14 | ACR 20 response is an improvement of greater than or equal to 20 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity \[based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities\] and CRP blood test to measure inflammation). |
| Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14 | Week 0 to Week 14 | DAS28 using CRP is a measure of tender and swollen joints (28 joints each) and the patient's assessment of disease activity. Values range from 0 (best) to 10 (worst). A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity. A Good response is defined as a patient with a DAS28 score of \<= 3.2 at Week 14 with improvement from Baseline in DAS28 score of \> 1.2. A Moderate response is defined as a patient with DAS28 score of \>3.2-5.1 at Week 14 with improvement from baseline in DAS28 score of \>1.2 or a DAS28 score of \<= 5.1 and improvement from baseline in DAS28 score of \>0.6 to 1.2 |
| Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14 | Weeks 0 to Week 14 | The SF-36 consists of 8 multi-item scales: limitations in physical functioning due to health problems, usual role activities due to physical health problems, bodily pain, usual role activities due to personal or emotional problems, social functioning due to physical or mental health problems, general mental health (psychological distress and well-being), vitality and general health perception. The values are 100=best to 0=worst. |
Countries
Argentina, Australia, Colombia, Germany, Hungary, Latvia, Lithuania, Malaysia, Malta, Mexico, New Zealand, Peru, Poland, Ukraine, United States
Participant flow
Recruitment details
The study was conducted at 86 investigational sites. The study population included 643 randomized participants from 15 countries.
Pre-assignment details
A total of 643 participants were randomized in the IV Period (Main Study). A total of 508 participants were randomized in the SC Period (Extension Study); participation in the SC Period was optional.
Participants by arm
| Arm | Count |
|---|---|
| 2mg/kg Golimumab+ MTX Participants received intravenous (IV) infusions of 2mg/kg golimumab at Week 0 and every 12 weeks for a minimum of 48 weeks followed by the option of subcutaneous (SC) injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, participants received methotrexate (MTX) at the same dose as before study entry. | 129 |
| 2mg/kg Golimumab Only Participants received IV infusions of 2mg/kg golimumab at Week 0 and every 12 weeks thereafter for a minimum of 48 weeks followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, participants received placebo (sham MTX) capsules during the IV Period only. | 128 |
| 4mg/kg Golimumab + MTX Participants received IV infusions of 4mg/kg golimumab at Week 0 and every 12 weeks for a minimum of 48 weeks followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, participants received MTX at the same dose as before study entry. | 128 |
| 4mg/kg Golimumab Only Participants received IV infusions of 4mg/kg golimumab at Week 0 and every 12 weeks for a minimum of 48 weeks followed by the option of SC injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition, participants received placebo (sham MTX) capsules during the IV Period only. | 129 |
| IV Placebo + MTX Participants received IV infusions of placebo at Week 0 and Week 12. At Week 24, depending on joint assessment results (dose regimen adjustment), participants were switched to IV infusions of 4mg/kg golimumab every 12 weeks for a minimum combined treatment period (placebo plus golimumab) of 48 weeks. This was followed by the option of subcutaneous (SC) injections of 50mg golimumab every 4 weeks for a further 24 weeks (Extension Study). In addition participants received MTX at the same dose as before study entry. Participants still receiving placebo infusions at Week 48 were not eligible to enter the Extension Study. | 129 |
| Total | 643 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| IV Period: Baseline to E0 | Adverse Event | 9 | 4 | 5 | 9 | 8 | 0 | 0 |
| IV Period: Baseline to E0 | Death | 1 | 1 | 1 | 1 | 0 | 0 | 0 |
| IV Period: Baseline to E0 | Discontinued oral study agent | 2 | 1 | 1 | 1 | 2 | 0 | 0 |
| IV Period: Baseline to E0 | Lack of Efficacy | 5 | 9 | 3 | 7 | 8 | 0 | 0 |
| IV Period: Baseline to E0 | Lost to Follow-up | 1 | 0 | 0 | 2 | 2 | 0 | 0 |
| IV Period: Baseline to E0 | Other | 2 | 9 | 9 | 3 | 2 | 0 | 0 |
| IV Period: Baseline to E0 | Protocol-prohibited medications | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| IV Period: Baseline to E0 | Worsening of RA | 0 | 5 | 1 | 4 | 2 | 0 | 0 |
| SC Period: Week E0 to Week E24 | Adverse Event | 0 | 2 | 1 | 2 | 0 | 0 | 2 |
| SC Period: Week E0 to Week E24 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| SC Period: Week E0 to Week E24 | Lack of Efficacy | 0 | 0 | 2 | 0 | 0 | 0 | 3 |
| SC Period: Week E0 to Week E24 | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 | 0 | 1 |
| SC Period: Week E0 to Week E24 | Other | 1 | 0 | 0 | 1 | 0 | 1 | 2 |
| SC Period: Week E0 to Week E24 | Worsening of RA | 0 | 1 | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 2mg/kg Golimumab+ MTX | 2mg/kg Golimumab Only | 4mg/kg Golimumab + MTX | 4mg/kg Golimumab Only | IV Placebo + MTX | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 49.7 years STANDARD_DEVIATION 11.1 | 49.9 years STANDARD_DEVIATION 11.86 | 49.6 years STANDARD_DEVIATION 10.96 | 48.4 years STANDARD_DEVIATION 12.66 | 50.2 years STANDARD_DEVIATION 11.28 | 49.4 years STANDARD_DEVIATION 11.65 |
| Sex: Female, Male Female | 99 Participants | 107 Participants | 103 Participants | 105 Participants | 103 Participants | 517 Participants |
| Sex: Female, Male Male | 30 Participants | 21 Participants | 25 Participants | 24 Participants | 26 Participants | 126 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 109 / 182 | 71 / 128 | 190 / 336 | 70 / 127 | 65 / 129 | 94 / 419 | 26 / 117 |
| serious Total, serious adverse events | 25 / 182 | 17 / 128 | 47 / 336 | 8 / 127 | 7 / 129 | 38 / 419 | 8 / 117 |
Outcome results
Primary
Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14
An ACR 50 response is defined as a greater than or equal to 50 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b. Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).
Time frame: Week 0 to Week 14
Population: Intent to treat (ITT). Patients considered non-responder if used any pre-specified prohibited medications or discontinued subcutaneous (SC) study agent due to lack of efficacy. Missing ACR components were imputed by Last Observation Carried Forward (LOCF) unless all ACR components are missing in which case considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: 2mg/kg Golimumab+ MTX | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14 | 28 Participants |
| Group II: 2mg/kg Golimumab Only | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14 | 16 Participants |
| Group III: 4mg/kg Golimumab + MTX | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14 | 27 Participants |
| Group IV: 4mg/kg Golimumab Only | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14 | 25 Participants |
| Group V: IV Placebo + MTX | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14 | 17 Participants |
| Group VI: Combined Groups I and III | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14 | 55 Participants |
| Group VII: Combined Groups II and IV | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 14 | 41 Participants |
Comparison: Hypothesis: Null hypothesis: No difference in ACR 50 response at Wk 14 comparing Groups V vs VI at 0.05 level of significance. Sample size: The sample size of 125 patients in each of the 5 randomized groups will provide at least 90 percentage power to detect a difference in the ACR 50 response rates between groups assuming 13 percentage response in Group V and \~29-31 percentage response in the Group VI at α = 0.05.p-value: 0.0512-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in ACR 50 response at Wk 14 comparing Groups I vs V at 0.05 level of significance. Sample size: The sample size of 125 patients in each of the 5 randomized groups will provide at least 90 percentage power to detect a difference in the ACR 50 response rates between groups assuming 13 percentage response in Group V and \~29-31% response in the Group I at α = 0.05.p-value: 0.0732-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in ACR 50 response at Wk 14 comparing Groups III vs V at 0.05 level of significance. Sample size: The sample size of 125 patients in each of the 5 randomized groups will provide at least 90 percentage power to detect a difference in the ACR 50 response rates between groups assuming 13 percentage response in Group V and \~29-31 percentage response in the Group III at α = 0.05.p-value: 0.0932-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in ACR 50 response at Wk 14 comparing Groups VII vs V at 0.05 level of significance. Sample size: The sample size of 125 patients in each of the 5 randomized groups will provide at least 90 percentage power to detect a difference in the ACR 50 response rates between groups assuming 13 percentage response in Group V and \~29-31 percentage response in the Group VII at α = 0.05.p-value: 0.4652-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in ACR 50 response at Wk 14 comparing Groups II vs V at 0.05 level of significance. Sample size: The sample size of 125 patients in each of the 5 randomized groups will provide at least 90 percentage power to detect a difference in the ACR 50 response rates between groups assuming 13 percentage response in Group V and \~29-31 percentage response in the Group II at α = 0.05.p-value: 0.8722-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in ACR 50 response at Wk 14 comparing Groups V vs I, V vs III, V vs II, and V vs IV at 0.05 level of significance. Sample size: The sample size of 125 patients in each of the 5 randomized groups will provide at least 90 percentage power to detect a difference in the ACR 50 response rates between groups assuming 13 percentage response in Group V and \~29-31 percentage response in the combined group (I and III) at α = 0.05.p-value: 0.1752-sided Cochran-Mantel-Haenszel
Secondary
Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14
DAS28 using CRP is a measure of tender and swollen joints (28 joints each) and the patient's assessment of disease activity. Values range from 0 (best) to 10 (worst). A score of higher than 5.1 indicates high disease activity, and a score below 3.2 indicates low disease activity. A Good response is defined as a patient with a DAS28 score of \<= 3.2 at Week 14 with improvement from Baseline in DAS28 score of \> 1.2. A Moderate response is defined as a patient with DAS28 score of \>3.2-5.1 at Week 14 with improvement from baseline in DAS28 score of \>1.2 or a DAS28 score of \<= 5.1 and improvement from baseline in DAS28 score of \>0.6 to 1.2
Time frame: Week 0 to Week 14
Population: Intent to treat. Patients considered non-responder if used any pre-specified prohibited medications or discontinued subcutaneous (SC) study agent due to lack of efficacy. Missing components were imputed by the median component value of all patients in the same stratum unless all components are missing in which case considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: 2mg/kg Golimumab+ MTX | Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14 | 89 Participants |
| Group II: 2mg/kg Golimumab Only | Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14 | 80 Participants |
| Group III: 4mg/kg Golimumab + MTX | Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14 | 94 Participants |
| Group IV: 4mg/kg Golimumab Only | Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14 | 83 Participants |
| Group V: IV Placebo + MTX | Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14 | 57 Participants |
| Group VI: Combined Groups I and III | Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14 | 183 Participants |
| Group VII: Combined Groups II and IV | Number of Participants With a Disease Activity Index Score 28 (Using C-reactive Protein)Moderate or Good Response at Week 14 | 163 Participants |
Comparison: Hypothesis: Null hypothesis: No difference in DAS28 response using CRP at Wk 14 comparing Groups V vs VI at 0.05 level of significance.p-value: <0.0012-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in DAS28 response using CRP at Wk 14 comparing Groups I vs V at 0.05 level of significance.p-value: <0.0012-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in DAS28 response using CRP at Wk 14 comparing Groups III vs V at 0.05 level of significance.p-value: <0.0012-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in DAS28 response using CRP at Wk 14 comparing Groups V vs VII at 0.05 level of significance.p-value: <0.0012-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in DAS28 response using CRP at Wk 14 comparing Groups II vs V at 0.05 level of significance.p-value: 0.0032-sided Cochran-Mantel-Haenszel
Comparison: Hypothesis: Null hypothesis: No difference in DAS28 response using CRP at Wk 14 comparing Groups V vs I, V vs III, V vs II, and V vs IV at 0.05 level of significance.p-value: 0.0012-sided Cochran-Mantel-Haenszel
Secondary
Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
ACR 20 response is an improvement of greater than or equal to 20 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity \[based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities\] and CRP blood test to measure inflammation).
Time frame: Week 0 to Week 14
Population: Intent to treat (ITT). Patients considered non-responder if used any pre-specified prohibited medications or discontinued subcutaneous (SC) study agent due to lack of efficacy. Missing ACR components were imputed by Last Observation Carried Forward (LOCF) unless all ACR components are missing in which case considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: 2mg/kg Golimumab+ MTX | Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14 | 71 Participants |
| Group II: 2mg/kg Golimumab Only | Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14 | 51 Participants |
| Group III: 4mg/kg Golimumab + MTX | Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14 | 66 Participants |
| Group IV: 4mg/kg Golimumab Only | Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14 | 62 Participants |
| Group V: IV Placebo + MTX | Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14 | 36 Participants |
| Group VI: Combined Groups I and III | Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14 | 137 Participants |
| Group VII: Combined Groups II and IV | Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14 | 113 Participants |
Comparison: Null hypothesis: No difference in ACR 20 response at Wk 14 comparing Groups V vs VI at 0.05 level of significance.p-value: <0.0012-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 20 response at Wk 14 comparing Groups I vs V at 0.05 level of significance.p-value: <0.0012-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 20 response at Wk 14 comparing Groups III vs V at 0.05 level of significance.p-value: <0.0012-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 20 response at Wk 14 comparing Groups V vs VII at 0.05 level of significance.p-value: 0.0022-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 20 response at Wk 14 comparing Groups II vs V at 0.05 level of significance.p-value: 0.0432-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 20 response at Wk 14 comparing Groups V vs I, V vs III, V vs II, and V vs IV at 0.05 level of significance.p-value: <0.0012-sided Cochran-Mantel-Haenszel
Secondary
Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24
ACR 50 response is an improvement of greater than or equal to 50 percentage from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments (patient's assessment of pain, patient's global assessemnt of disease activity, Physician's global assessment of disease activity (based on a scale of 0=no disease to 10=severe disease), HAQ (20 questions on life activities) and CRP blood test to measure inflammation).
Time frame: Week 0 to Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: 2mg/kg Golimumab+ MTX | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | 24 Participants |
| Group II: 2mg/kg Golimumab Only | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | 11 Participants |
| Group III: 4mg/kg Golimumab + MTX | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | 32 Participants |
| Group IV: 4mg/kg Golimumab Only | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | 15 Participants |
| Group V: IV Placebo + MTX | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | 12 Participants |
| Group VI: Combined Groups I and III | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | 56 Participants |
| Group VII: Combined Groups II and IV | Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24 | 26 Participants |
Comparison: Null hypothesis: No difference in ACR 50 response at Week 24 comparing Groups V vs VI at 0.05 level of significance.p-value: 0.0022-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 50 response at Week 24 comparing Groups I vs V at 0.05 level of significance.p-value: 0.0322-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 50 response at Week 24 comparing Groups III vs V at 0.05 level of significance.p-value: <0.0012-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 50 response at Week 24 comparing Groups V vs VII at 0.05 level of significance.p-value: 0.7952-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 50 response at Week 24 comparing Groups II vs V at 0.05 level of significance.p-value: 0.8442-sided Cochran-Mantel-Haenszel
Comparison: Null hypothesis: No difference in ACR 50 response at Week 24 comparing Groups V vs I, V vs III, V vs II, and V vs IV at 0.05 level of significance.p-value: 0.542-sided Cochran-Mantel-Haenszel
Secondary
Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14
The SF-36 consists of 8 multi-item scales: limitations in physical functioning due to health problems, usual role activities due to physical health problems, bodily pain, usual role activities due to personal or emotional problems, social functioning due to physical or mental health problems, general mental health (psychological distress and well-being), vitality and general health perception. The values are 100=best to 0=worst.
Time frame: Weeks 0 to Week 14
Population: Intent to treat (ITT). Missing components were imputed by the median component value of all patients in the same Stratum at baseline, and last observation carried forward (LOCF) at Week 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I: 2mg/kg Golimumab+ MTX | Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14 | 6.92 Units on a scale | Standard Deviation 9.175 |
| Group II: 2mg/kg Golimumab Only | Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14 | 4.03 Units on a scale | Standard Deviation 7.462 |
| Group III: 4mg/kg Golimumab + MTX | Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14 | 6.76 Units on a scale | Standard Deviation 8.252 |
| Group IV: 4mg/kg Golimumab Only | Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14 | 5.14 Units on a scale | Standard Deviation 9.674 |
| Group V: IV Placebo + MTX | Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14 | 4.27 Units on a scale | Standard Deviation 7.216 |
| Group VI: Combined Groups I and III | Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14 | 6.84 Units on a scale | Standard Deviation 8.702 |
| Group VII: Combined Groups II and IV | Physical Component Summary (PCS) Score of the Short Form-36 (SF-36) at Week 14 | 4.58 Units on a scale | Standard Deviation 8.644 |
Comparison: Hypothesis: Null hypothesis: No difference in change from baseline in PCS score of SF-36 at Wk 14 comparing Groups V vs VI at 0.05 level of significance.p-value: 0.0052-sided ANOVA on van der Waerden
Comparison: Hypothesis: Null hypothesis: No difference in change from baseline in PCS score of SF-36 at Wk 14 comparing Groups I vs V at 0.05 level of significance.p-value: 0.0142-sided ANOVA on van der Waerden
Comparison: Hypothesis: Null hypothesis: No difference in change from baseline in PCS score of SF-36 at Wk 14 comparing Groups III vs V at 0.05 level of significance.p-value: 0.0142-sided ANOVA on van der Waerden
Comparison: Hypothesis: Null hypothesis: No difference in change from baseline in PCS score of SF-36 at Wk 14 comparing Groups I and VII at 0.05 level of significance.p-value: 0.9962-sided ANOVA on van der Waerden
Comparison: Hypothesis: Null hypothesis: No difference in change from baseline in PCS score of SF-36 at Wk 14 comparing Groups II vs V at 0.05 level of significance.p-value: 0.7382-sided ANOVA on van der Waerden
Comparison: Hypothesis: Null hypothesis: No difference in change from baseline in PCS score of SF-36 at Wk 14 comparing Groups V vs I, V vs III, V vs II, and V vs IV at 0.05 level of significance.p-value: 0.7882-sided ANOVA on van der Waerden