Trial Outcomes & Findings for A Study of Adalimumab When Added to Inadequate Standard Anti-rheumatic Therapy in Patients With Active Rheumatoid Arthritis (NCT NCT01231321)

Last Updated: 2011-04-26

Results Overview

Serious adverse events were collected from the time of informed consent, and nonserious adverse events were collected from the time of first dose of adalimumab, until 70 days after the last injection of adalimumab. Refer to the Reported Adverse Events section of this results disclosure for specific adverse events reported. Note: Severe events considerably interfered in patients' usual activities and may have been life-threatening. Serious events were life-threatening; resulted in hospitalization, congenital anomalies, or disability; or required intervention to prevent seriousness.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

100 participants

Primary outcome timeframe

Up to 34 weeks (24 week study treatment plus 70-day follow-up period)

Results posted on

2011-04-26

Participant Flow

Participant milestones

Participant milestones
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.
Overall Study STARTED	100
Overall Study COMPLETED	95
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.
Overall Study Adverse Event	3
Overall Study Lack of Efficacy	2

Baseline Characteristics

A Study of Adalimumab When Added to Inadequate Standard Anti-rheumatic Therapy in Patients With Active Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL n=100 Participants Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	90 Participants n=99 Participants
Age, Categorical >=65 years	10 Participants n=99 Participants
Age Continuous	50.9 years STANDARD_DEVIATION 11.1 • n=99 Participants
Sex: Female, Male Female	89 Participants n=99 Participants
Sex: Female, Male Male	11 Participants n=99 Participants
Region of Enrollment Russian Federation	100 participants n=99 Participants

PRIMARY outcome

Timeframe: Up to 34 weeks (24 week study treatment plus 70-day follow-up period)

Population: All enrolled subjects were included in this intent-to-treat (ITT) analysis.

Outcome measures

Outcome measures
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL n=100 Participants Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.	Change From Abnormal to Normal Subjects whose physical examination findings for the categories below were abnormal at Baseline and normal at 24 weeks
Frequency of Adverse Events Adverse events	38 participants	—
Frequency of Adverse Events Serious adverse events	1 participants	—
Frequency of Adverse Events Severe adverse events	1 participants	—
Frequency of Adverse Events Possibly or probably related to adalimumab	24 participants	—
Frequency of Adverse Events Adverse events leading to discontinuation	3 participants	—
Frequency of Adverse Events Fatal adverse events	0 participants	—

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: All enrolled subjects with available data were included in this intent-to-treat (ITT) analysis.

Physical examination findings were compared between Baseline and Week 24, and changes were recorded (Normal at Baseline to Abnormal at Week 24; or Abnormal at Baseline to Normal at Week 24). Physical examination criteria (normal vs. abnormal) were at the clinical judgement of the examining physician. Significant changes in physical examination from Baseline were considered to be adverse events.

Outcome measures

Outcome measures
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL n=99 Participants Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.	Change From Abnormal to Normal n=99 Participants Subjects whose physical examination findings for the categories below were abnormal at Baseline and normal at 24 weeks
Changes of Physical Examination General Appearance	0 participants	0 participants
Changes of Physical Examination Head	0 participants	0 participants
Changes of Physical Examination Ears	0 participants	0 participants
Changes of Physical Examination Eyes	1 participants	0 participants
Changes of Physical Examination Nose	0 participants	0 participants
Changes of Physical Examination Throat	0 participants	0 participants
Changes of Physical Examination Neck	0 participants	0 participants
Changes of Physical Examination Thyroid	0 participants	0 participants
Changes of Physical Examination Lungs/Chest	0 participants	0 participants
Changes of Physical Examination Cardiovascular	1 participants	0 participants
Changes of Physical Examination Abdomen	0 participants	0 participants
Changes of Physical Examination Musculoskeletal	0 participants	0 participants
Changes of Physical Examination Extremities	0 participants	0 participants
Changes of Physical Examination Skin	0 participants	1 participants
Changes of Physical Examination Lymph nodes	1 participants	1 participants
Changes of Physical Examination Neurological	0 participants	0 participants
Changes of Physical Examination Genitourinary	0 participants	0 participants
Changes of Physical Examination Other	0 participants	0 participants

PRIMARY outcome

Timeframe: 24 weeks

Population: All subjects with available data were included in this intent-to-treat (ITT) analysis. The number of subjects with available data is indicated for each laboratory assessment.

Laboratory values were assessed for values above and below the normal (reference) ranges used by the central laboratory. Note abbreviations used in table: Alk. phosphatase = alkaline phosphatase, ALT = alanine aminotransferase, AST = aspartate aminotransferase, ESR = erythrocyte sedimentation rate

Outcome measures

Outcome measures
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL n=100 Participants Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.	Change From Abnormal to Normal n=100 Participants Subjects whose physical examination findings for the categories below were abnormal at Baseline and normal at 24 weeks
Deviation From Normal Laboratory Ranges AST (ref. range 0 - 31 U/L) (n = 97)	0 participants	6 participants
Deviation From Normal Laboratory Ranges Calcium (ref. range 2 - 3 mmol/L) (n = 97)	1 participants	0 participants
Deviation From Normal Laboratory Ranges Chloride (ref. range 98 - 107 mEq/L) (n = 96)	0 participants	0 participants
Deviation From Normal Laboratory Ranges Creatine kinase (ref. range 0 - 167 U/L) (n = 97)	0 participants	2 participants
Deviation From Normal Laboratory Ranges Creatinine (ref. range 53 - 97 mcmol/L) (n = 97)	1 participants	1 participants
Deviation From Normal Laboratory Ranges C-reactive protein (ref. range 0-5 mg/L) (n = 97)	0 participants	45 participants
Deviation From Normal Laboratory Ranges Glucose (ref. range 4- 6 mmol/L) (n = 97)	4 participants	10 participants
Deviation From Normal Laboratory Ranges Potassium (ref. range 4 - 6 mmol/L) (n = 97)	21 participants	0 participants
Deviation From Normal Laboratory Ranges Sodium (ref. range 136 - 145 mmol/L) (n = 97)	2 participants	0 participants
Deviation From Normal Laboratory Ranges Total bilirubin (ref. range 3-20 mcmol/L) (n = 97)	0 participants	5 participants
Deviation From Normal Laboratory Ranges Total cholesterol (ref. range 4-8 mmol/L) (n = 97)	5 participants	4 participants
Deviation From Normal Laboratory Ranges Total protein (ref. range 64-83 g/L) (n = 97)	3 participants	2 participants
Deviation From Normal Laboratory Ranges Urea (ref. range 2 - 6 mmol/L) (n = 96)	0 participants	30 participants
Deviation From Normal Laboratory Ranges Urea nitrogen (ref. range 6 - 20 mg/dL) (n = 97)	0 participants	11 participants
Deviation From Normal Laboratory Ranges Uric acid (ref. range 150 - 350 mcmol/L) (n = 97)	11 participants	6 participants
Deviation From Normal Laboratory Ranges Urine pH (ref. range 5 - 8) (n = 98)	0 participants	1 participants
Deviation From Normal Laboratory Ranges Basophils (%) (ref. range: 0% - 1%) (n = 95)	0 participants	0 participants
Deviation From Normal Laboratory Ranges Basophils (ref. range 0 - 2 x 10^9/L) (n = 94)	0 participants	0 participants
Deviation From Normal Laboratory Ranges Eosinophils (%) (ref. range 1% - 5%) (n = 95)	17 participants	11 participants
Deviation From Normal Laboratory Ranges Eosinophils (ref. range 0 - 1 x 10^9/L) (n = 94)	0 participants	0 participants
Deviation From Normal Laboratory Ranges Erythrocytes (ref. range 4 - 5 x 10^12/L) (n = 95)	15 participants	9 participants
Deviation From Normal Laboratory Ranges ESR (ref. range 0 - 30 mm/h) (n = 75)	0 participants	14 participants
Deviation From Normal Laboratory Ranges Hematocrit (ref. range 35% - 47%) (n = 95)	15 participants	2 participants
Deviation From Normal Laboratory Ranges Hemoglobin (ref. range 12 - 16 g/dL) (n = 95)	33 participants	1 participants
Deviation From Normal Laboratory Ranges Leucocytes (ref. range 4 - 11 x 10^3/L) (n = 95)	3 participants	10 participants
Deviation From Normal Laboratory Ranges Lymphocytes (%) (ref. range 19% - 37%) (n = 95)	15 participants	24 participants
Deviation From Normal Laboratory Ranges Lymphocytes (ref. range 2 - 4 x 10^9/L) (n = 94)	44 participants	6 participants
Deviation From Normal Laboratory Ranges Monocytes (%) (ref. range 3% - 11%) (n = 95)	1 participants	12 participants
Deviation From Normal Laboratory Ranges Monocytes (ref. range 0 - 1 x 10^9/L) (n = 94)	0 participants	6 participants
Deviation From Normal Laboratory Ranges Neutrophils (%) (ref. range 48% - 78%) (n = 95)	20 participants	6 participants
Deviation From Normal Laboratory Ranges Neutrophils (ref. range 2 - 9 x 10^9/L) (n = 95)	5 participants	3 participants
Deviation From Normal Laboratory Ranges Platelets (ref. range 150-400 x 10^3/mcL) (n = 95)	0 participants	9 participants
Deviation From Normal Laboratory Ranges Albumin (ref. range 35 - 50 g/L) (n = 97)	0 participants	14 participants
Deviation From Normal Laboratory Ranges Alk. phosphatase (ref. range 40-150 U/L) (n = 97)	1 participants	2 participants
Deviation From Normal Laboratory Ranges ALT (ref. range 0 - 31 U/L) (n = 97)	0 participants	9 participants

PRIMARY outcome

Timeframe: 24 weeks

Population: All subjects with available data were included in this intent-to-treat (ITT) analysis.

Vital signs values were assessed for values above and below the normal (reference) ranges used by the central laboratory. Note, in table, BP = blood pressure.

Outcome measures

Outcome measures
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL n=99 Participants Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.	Change From Abnormal to Normal n=99 Participants Subjects whose physical examination findings for the categories below were abnormal at Baseline and normal at 24 weeks
Vital Sign Values Body temperature (ref. range 36 - 37 degrees C)	1 participants	0 participants
Vital Sign Values Systolic BP (ref. range 100 - 140 mm Hg)	1 participants	2 participants
Vital Sign Values Diastolic BP (ref. range 60 - 100 mm Hg)	0 participants	0 participants
Vital Sign Values Pulse (ref. range 50 - 90 beats/min)	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: All subjects with data available from both Baseline and Week 24 were included in this intent-to-treat (ITT) analysis.

The DAS28 is validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health (patient's global assessment of disease activity) were included in the DAS28 score. Scores on the DAS28 range from 1 (inactive disease) to 10 (very active disease).

Outcome measures

Outcome measures
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL n=96 Participants Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.	Change From Abnormal to Normal Subjects whose physical examination findings for the categories below were abnormal at Baseline and normal at 24 weeks
Change in Disease Activity Score (DAS28) Compared With Baseline	-2.74 units on a scale Standard Deviation 1.18	—

Adverse Events

Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL n=100 participants at risk Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.
Infections and infestations Pyogenic arthritis	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.

Other adverse events

Other adverse events
Measure	Adalimumab/ Pre-filled Syringe 40 mg/0.8 mL n=100 participants at risk Adalimumab 40 mg in 0.8 ml in pre-filled syringe for under the skin of the abdomen or the thigh injection every other week.
General disorders Adverse drug reaction	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Skin and subcutaneous tissue disorders Angioedema	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Arthritis bacterial	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
General disorders Asthenia	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Musculoskeletal and connective tissue disorders Back pain	2.0% 2/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Investigations Body temperature increased	2.0% 2/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Bronchitis	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Skin and subcutaneous tissue disorders Dermatitis	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Ear infection	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Reproductive system and breast disorders Endometriosis	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Blood and lymphatic system disorders Eosinophilia	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Furuncle	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Gastroenteritis	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Nervous system disorders Headache	3.0% 3/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Herpes zoster	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Herpex simplex	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
General disorders Injection site erythema	3.0% 3/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
General disorders Injection site pain	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
General disorders Injection site papule	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
General disorders Injection site pruritus	2.0% 2/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Blood and lymphatic system disorders Leukopenia	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Blood and lymphatic system disorders Lymphadenopathy	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Blood and lymphatic system disorders Lymphocytosis	2.0% 2/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Musculoskeletal and connective tissue disorders Myalgia	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Nasopharyngitis	4.0% 4/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Blood and lymphatic system disorders Neutropenia	2.0% 2/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Oral herpes	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Musculoskeletal and connective tissue disorders Osteochondrosis	3.0% 3/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
General disorders Pain	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Skin and subcutaneous tissue disorders Photosensitivity reaction	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Pneumonia	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
General disorders Pyrexia	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Skin and subcutaneous tissue disorders Rash	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	4.0% 4/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Respiratory tract infection viral	3.0% 3/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Eye disorders Retinopathy	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	3.0% 3/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Skin and subcutaneous tissue disorders Rosacea	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Vascular disorders Thrombophlebitis	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Tracheitis	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Upper respiratory tract infection	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Skin and subcutaneous tissue disorders Urticaria	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.
Infections and infestations Wound infection	1.0% 1/100 • Adverse events were collected from the time of informed consent up to 70 days after the last injection of adalimumab.

Additional Information

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