The purpose of this exploratory sub-study was to evaluate from a clinical perspective the impact on disease activity of lowering the dose of abatacept from 10 mg/kg to 5 mg/kg in subjects who had achieved remission (Disease Activity Score 28 \[DAS 28\]-erythrocyte sedimentation rate \[ESR\] \< 2.6) at Day 701 of study IM101023.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
108
Time to Disease Relapse Through Month 12 (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse)
An event of disease relapse was defined as additional Disease-modifying antirheumatic drug (DMARD) therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 C-reactive protein (CRP) score \>=3.2 at 2 consecutive visits. Time to disease relapse was evaluated using life tables (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse).
Time frame: Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Number of Participants Experiencing Disease Relapse
Disease relapse is defined as additional DMARD therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 CRP score \>= 3.2 at 2 consecutive visits.
Time frame: After 12 Months of treatment
Mean Time-Matched Baseline DAS28 CRP Scores
Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (\>5.1=high disease activity; \<3.2=low disease activity; \<2.6=remission).
Time frame: Baseline
Adjusted Mean Change From Baseline in DAS28 CRP During Double-Blind Treatment
Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (\>5.1=high disease activity; \<3.2=low disease activity; \<2.6=remission).
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Time frame: Baseline, Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
Percentage of Participants With 2 Consecutive DAS 28 CRP Scores ≥ 3.2 (Loss of Low Disease Activity Status)
DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (\>5.1=high disease activity; \<3.2=low disease activity; \<2.6=remission).
Time frame: After 12 months of treatment
Percentage of Participants Given Additional DMARD Therapy During Double-Blind Treatment
Additional DMARD therapy is defined as a re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD.
Time frame: After 12 months of treatment
Percentage of Participants Who at Any Time During Double-Blind Treatment Were Given 2 or More Courses of High-Dose Steroids
A course of high dose steroids is defined as a course of intramuscular, intravenous, or high dose oral corticosteroids (use of \> 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals).
Time frame: After 12 months of treatment
Percentage of Participants Given Rescue Medication Therapy During Double-Blind Treatment
All subjects in the sub-study randomized to receive double-blind abatacept 5 mg/kg or 10 mg/kg. Subjects rescued to open-label treatment received abatacept 10 mg/kg.
Time frame: After 12 months of treatment
Percentage of Participants Who Modified Therapy During Double-Blind Treatment
Modified therapy=additional DMARD therapy, 2 or more courses of high dose steroids or rescue medication. Additional DMARD therapy=re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD. A course of high dose steroids=a course of intramuscular, intravenous, or high dose oral corticosteroids (use of \> 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals). Rescue medication=abatacept 10 mg/kg.
Time frame: After 12 months of treatment
Percentage of Participants Who Lost Remission Status
Loss of remission is defined as DAS 28 CRP \>=2.6.
Time frame: After 12 months of treatment
Steady-state Trough Serum Concentration (Cmin) of Abatacept During Double-Blind Treatment
Time frame: Day 701 of the main study; sub-study Days 1, 85, 169, 253
Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations During Double-Blind Treatment
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time frame: From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)
Percentage of Participants With Infection and Infestation AEs Reported During Double-Blind Treatment
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Infection and Infestation AEs = any AE within the System Organ Class Infection and Infestation.
Time frame: From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)
Percentage of Participants With Malignant Neoplasms Reported During Double-Blind Treatment
All neoplasms were assessed by medical review as to whether or not the event was malignant.
Time frame: From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)
Percentage of Participants With Prespecified Acute Infusional Adverse Events (AIAEs) During Double-Blind Treatment, by Intensity
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Acute Infusional AE= a subset of the peri-infusional AEs with onset during the first hour after the start of the study drug infusion. A total of 105 infusional events were prespecified in the protocol.
Time frame: From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)
Percentage of Participants With Prespecified Peri-Infusional Adverse Events (PAIAEs) During Double-Blind Treatment, by Intensity
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Peri-infusional AE=a pre-specified infusional AE occuring during the first 24 hours after the start of study drug infusion.A total of 105 infusional events were prespecified in the protocol. GDASC=General Disorders and Administration Site Conditions, RTMD=Respiratory, Thoracic and Mediastinal Disorders.
Time frame: From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)
Percentage of Participants With Pre-specified Autoimmune Disorders (ADs) Reported During Double-Blind Treatment, by Intensity
A total of 127 autoimmune disorders were prespecified in the protocol. MCTD=Musculoskeletal and Connective Tissue Disorders
Time frame: From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)
Percentage of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During Double-Blind Treatment
Not evaluated: high hemoglobin,high hematocrit,high erythrocytes,high neutrophils+bands(N+B),low monocytes,low basophils,low eosinophils,low alkaline phosphatase(ALP),low aspartate aminotransferase(AST),low alanine aminotransferase(ALT),low G-Glutamyl transferase(GGT),low total bilirubin,low blood urea nitrogen,low creatinine,high albumin,low uric acid,low urine protein,low urine glucose,low urine blood,low urine leukocyte esterase,low urine white blood cells,low red blood cells.Pre Rx=pretreatment,(\*)Lymphocytes(c/uL):Low\<.750x10\^3,High\>7.50x10\^3.(\*)Eosinophils:\>.750x10\^3 c/uL.
Time frame: From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)
Clinically Significant Changes in Vital Signs and Physical Findings
Clinical significance was determined by investigator. Parameters include blood pressure, heart rate, respiration rate, and temperature.
Time frame: From start of substudy up to 56 days post last dose in the double-blind period or start of the open-label rescue period, whichever occurred first until end of study (study duration was 115 weeks)
Participants With Positive Antibody Responses to Abatacept (Electrochemiluminescence [ECL] Method) During Double-Blind Treatment
A positive antibody response to Abatacept (measured by the ECL assay) is further classified as a positive response for either Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Possibly immunoglobulin (Ig)' or 'Ig and/or Junction Region'
Time frame: After 12 months of treatment