Special Investigation of Humira® (Adalimumab) on Long-term Treatment in Patients With Rheumatoid Arthritis

• Sponsor: AbbVie (prior sponsor, Abbott) (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01163318
• Collaborator: (none)
• Enrollment: 552
• Duration (Months): 53

Study Details

Study Description

Brief Summary

The purpose of this study was to collect data on the incidence of adverse drug reactions, infections and malignant tumors, as well as factors that might affect the safety and effectiveness of Humira® (adalimumab; 40mg/0.8 mL) in Japanese participants who received the drug for the treatment of rheumatoid arthritis.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis

Detailed Description

Rheumatoid arthritis is a chronic autoimmune disease which requires long-term treatment. Due to the need of long-term safety data in Japanese participants and to fulfil the conditions of approval of adalimumab by the Japanese regulatory authority, this post-marketing observational study (PMOS) was conducted. The study investigated the long-term safety of adalimumab, particularly associated with the development of infections and malignant tumors. Data was collected once every 6 months up to 3 years.

Study Design

• Study Type: Observational
• Actual Enrollment: 552 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Special Investigation (Long-term Treatment in Patients With Rheumatoid Arthritis)
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Adalimumab 40 mg/0.8 mL syringe for subcutaneous injection Participants with rheumatoid arthritis who received adalimumab, per approved label

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Drug Reactions (ADRs) [From the initiation of adalimumab treatment, every 6 months up to 3 years.]

   An ADR was any unfavourable or unintended response (adverse event) that could possibly be related to adalimumab treatment. ADRs were assessed and data are presented as percentage of participants.

Secondary Outcome Measures

1. Incidence of Infections and Malignant Tumors [From the initiation of adalimumab treatment, every 6 months up to 3 years.]

   Participants were evaluated for the presence/absence of malignant tumors and infections. Data are presented as percentage of participants.

2. Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit [Baseline (Week 0), Week 4, Week 12, Week 24, Year 1, Year 1.5, Year 2, Year 2.5, and Year 3]

   DAS28-4ESR, a combined index that measured activity of rheumatoid arthritis, was calculated based on: (1) the number of tender joints among 28 joints evaluated; (2) the number of swollen joints among 28 joints evaluated; (3) general health evaluated by a visual analog scale (VAS); and (4) ESR. DAS28-4ESR scores ranged from 0 (no disease activity) to 10 (maximal disease activity); decrease in DAS28-4ESR scores indicate improvement of disease. DAS28-4ESR score < 2.6 was defined as clinical remission of rheumatoid arthritis. Data are presented as percentage of participants.

3. Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit [Baseline (Week 0), Week 24, Year 1, Year 1.5, Year 2, Year 2.5, and Year 3]

   MHAQ was a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatic diseases. Participants assessed their ability to do each task over the past 6 months using the following response categories (score): without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score from 0 to 3, where 0 represented no disability and 3 very severe, high-dependency disability. MHAQ score ≤ 0.5 was defined as clinical remission, signifying normal physical function. Data are presented as percentage of participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Participants who received adalimumab in accordance with its indications for treatment and dosage regimens.

2. Participants who used adalimumab continuously.

3. Participants without current or past history of malignant tumors.

4. Participants evaluated for Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR).

5. Participants evaluated by Health Assessment Questionnaire (HAQ) or Modified Health Assessment Questionnaire (MHAQ) prior to the initiation of adalimumab treatment in the all-case PMOS.

Exclusion criteria:

1. Contraindications according to the package insert.

2. Participants with serious infections.

3. Participants with tuberculosis.

4. Participants with a history of hypersensitivity to any ingredient of adalimumab.

5. Participants with demyelinating disease or a history of demyelinating disease.

6. Participants with congestive cardiac failure.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie (prior sponsor, Abbott)

Investigators

• Study Director: Sarina Kurimoto, AbbVie GK.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01163318
• Other Study ID Numbers: P12-070
• First Posted: Jul 15, 2010
• Last Update Posted: Jun 10, 2015
• Last Verified: May 1, 2015

• Keywords provided by AbbVie (prior sponsor, Abbott): Rheumatoid Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Pre-assignment Detail	The primary reason for discontinuation was not collected for 224 participants listed under the category of 'multiple reasons per participant' (Insufficient effect (n=76), other reasons (n=43), economic reasons (n=2), AEs (n=41), no further visits (including change of hospital) (n=39), discontinued by the patient request (n=17), and unknown (n=8)).

Arm/Group Title	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
Arm/Group Description	Participants with rheumatoid arthritis who received adalimumab, per approved label
Period Title: Overall Study
STARTED	552
COMPLETED	284
NOT COMPLETED	268

Baseline Characteristics

Arm/Group Title	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
Arm/Group Description	Participants with rheumatoid arthritis who received adalimumab, per approved label
Overall Participants	508
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.5 (13.4)
Sex: Female, Male (Count of Participants)
Female	416 81.9%
Male	92 18.1%

Outcome Measures

1. Primary Outcome

Title	Incidence of Adverse Drug Reactions (ADRs)
Description	An ADR was any unfavourable or unintended response (adverse event) that could possibly be related to adalimumab treatment. ADRs were assessed and data are presented as percentage of participants.
Time Frame	From the initiation of adalimumab treatment, every 6 months up to 3 years.

Outcome Measure Data

Analysis Population Description

Safety analysis set, defined as participants who did not violate protocol criteria.

Arm/Group Title	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
Arm/Group Description	Participants with rheumatoid arthritis who received adalimumab, per approved label
Measure Participants	508
Number [Percentage of participants]	33.3 6.6%

2. Secondary Outcome

Title	Incidence of Infections and Malignant Tumors
Description	Participants were evaluated for the presence/absence of malignant tumors and infections. Data are presented as percentage of participants.
Time Frame	From the initiation of adalimumab treatment, every 6 months up to 3 years.

Outcome Measure Data

Analysis Population Description

Safety analysis set, defined as participants who did not violate protocol criteria.

Arm/Group Title	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
Arm/Group Description	Participants with rheumatoid arthritis who received adalimumab, per approved label
Measure Participants	508
Infections	16.1 3.2%
Malignant Tumors	1.2 0.2%

3. Secondary Outcome

Title	Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit
Description	DAS28-4ESR, a combined index that measured activity of rheumatoid arthritis, was calculated based on: (1) the number of tender joints among 28 joints evaluated; (2) the number of swollen joints among 28 joints evaluated; (3) general health evaluated by a visual analog scale (VAS); and (4) ESR. DAS28-4ESR scores ranged from 0 (no disease activity) to 10 (maximal disease activity); decrease in DAS28-4ESR scores indicate improvement of disease. DAS28-4ESR score < 2.6 was defined as clinical remission of rheumatoid arthritis. Data are presented as percentage of participants.
Time Frame	Baseline (Week 0), Week 4, Week 12, Week 24, Year 1, Year 1.5, Year 2, Year 2.5, and Year 3

Outcome Measure Data

Analysis Population Description

Efficacy analysis set, defined as safety analysis set excluding participants without evaluable DAS28-4ESR score and lack of Modified Health Assessment Questionnaire (MHAQ) data prior to drug administration.

Arm/Group Title	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
Arm/Group Description	Participants with rheumatoid arthritis who received adalimumab, per approved label
Measure Participants	429
Baseline (Week 0)	2.8 0.6%
Week 4	14.5 2.9%
Week 12	20.0 3.9%
Week 24	29.6 5.8%
Year 1	33.6 6.6%
Year 1.5	37.1 7.3%
Year 2	36.6 7.2%
Year 2.5	38.2 7.5%
Year 3	36.4 7.2%

4. Secondary Outcome

Title	Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit
Description	MHAQ was a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatic diseases. Participants assessed their ability to do each task over the past 6 months using the following response categories (score): without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score from 0 to 3, where 0 represented no disability and 3 very severe, high-dependency disability. MHAQ score ≤ 0.5 was defined as clinical remission, signifying normal physical function. Data are presented as percentage of participants.
Time Frame	Baseline (Week 0), Week 24, Year 1, Year 1.5, Year 2, Year 2.5, and Year 3

Outcome Measure Data

Analysis Population Description

Efficacy analysis set, defined as safety analysis set excluding participants without evaluable DAS28-4ESR score and lack of Modified Health Assessment Questionnaire (MHAQ) data prior to drug administration.

Arm/Group Title	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
Arm/Group Description	Participants with rheumatoid arthritis who received adalimumab, per approved label
Measure Participants	426
Baseline (Week 0)	43.4 8.5%
Week 24	53.5 10.5%
Year 1	63.6 12.5%
Year 1.5	63.6 12.5%
Year 2	66.0 13%
Year 2.5	65.7 12.9%
Year 3	66.2 13%

Adverse Events

Time Frame	From the initiation of adalimumab treatment, every 6 months up to 3 years.
Adverse Event Reporting Description	The occurrence, type of adverse events, date of onset, seriousness (reasons for serious events), outcome (type of outcome and date of evaluation), measures taken regarding adalimumab and use of symptomatic treatment, causal relationship between adalimumab and adverse events, and laboratory findings were assessed.
Arm/Group Title	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
Arm/Group Description	Participants with rheumatoid arthritis who received adalimumab, per approved label
All Cause Mortality
	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
	Affected / at Risk (%)	# Events
Total	86/508 (16.9%)
Blood and lymphatic system disorders
Anaemia	1/508 (0.2%)
Disseminated intravascular coagulation	1/508 (0.2%)
Iron deficiency anaemia	1/508 (0.2%)
Lymphadenopathy	1/508 (0.2%)
Pancytopenia	1/508 (0.2%)
Splenic lesion	1/508 (0.2%)
Cardiac disorders
Acute myocardial infarction	1/508 (0.2%)
Cardiac failure	1/508 (0.2%)
Myocardial infarction	1/508 (0.2%)
Ear and labyrinth disorders
Vertigo	1/508 (0.2%)
Gastrointestinal disorders
Enterocolitis	1/508 (0.2%)
Pancreatitis acute	1/508 (0.2%)
Diverticular perforation	1/508 (0.2%)
General disorders
Pyrexia	1/508 (0.2%)
Abasia	1/508 (0.2%)
Deformity	1/508 (0.2%)
Hepatobiliary disorders
Hepatic function abnormal	2/508 (0.4%)
Non-alcoholic steatohepatitis	1/508 (0.2%)
Immune system disorders
Amyloidosis	1/508 (0.2%)
Sarcoidosis	1/508 (0.2%)
Infections and infestations
Acute tonsillitis	1/508 (0.2%)
Atypical pneumonia	1/508 (0.2%)
Bronchitis	1/508 (0.2%)
Bronchopneumonia	1/508 (0.2%)
Epstein-Barr virus infection	1/508 (0.2%)
Erysipelas	1/508 (0.2%)
Herpes zoster	2/508 (0.4%)
Listeriosis	1/508 (0.2%)
Lung abscess	1/508 (0.2%)
Meningitis	1/508 (0.2%)
Peritonitis	1/508 (0.2%)
Pneumonia	5/508 (1%)
Pneumonia haemophilus	1/508 (0.2%)
Pneumonia mycoplasmal	1/508 (0.2%)
Pneumonia pneumococcal	1/508 (0.2%)
Pneumonia streptococcal	1/508 (0.2%)
Pulmonary mycosis	1/508 (0.2%)
Pyelonephritis	1/508 (0.2%)
Pyelonephritis acute	1/508 (0.2%)
Sepsis	2/508 (0.4%)
Skin infection	1/508 (0.2%)
Subcutaneous abscess	1/508 (0.2%)
Urinary tract infection	1/508 (0.2%)
Arthritis bacterial	1/508 (0.2%)
Enteritis infectious	2/508 (0.4%)
Pneumonia bacterial	4/508 (0.8%)
Purulence	1/508 (0.2%)
Pneumonia cryptococcal	1/508 (0.2%)
Injury, poisoning and procedural complications
Femoral neck fracture	1/508 (0.2%)
Foot fracture	1/508 (0.2%)
Fracture	1/508 (0.2%)
Radius fracture	1/508 (0.2%)
Spinal compression fracture	5/508 (1%)
Subdural haematoma	1/508 (0.2%)
Tibia fracture	1/508 (0.2%)
Ulna fracture	1/508 (0.2%)
Contusion	1/508 (0.2%)
Lower limb fracture	1/508 (0.2%)
Pubis fracture	1/508 (0.2%)
Investigations
Computerised tomogram thorax abnormal	1/508 (0.2%)
Metabolism and nutrition disorders
Decreased appetite	2/508 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/508 (0.4%)
Arthritis	2/508 (0.4%)
Lumbar spinal stenosis	1/508 (0.2%)
Rheumatoid arthritis	6/508 (1.2%)
Spinal column stenosis	1/508 (0.2%)
Spinal osteoarthritis	1/508 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	2/508 (0.4%)
Gastric cancer	1/508 (0.2%)
Neuroendocrine carcinoma of the skin	1/508 (0.2%)
Lung cancer metastatic	1/508 (0.2%)
Lung neoplasm malignant	2/508 (0.4%)
Prostate cancer	1/508 (0.2%)
Nervous system disorders
Anxiety disorder	1/508 (0.2%)
Cerebral infarction	3/508 (0.6%)
Renal and urinary disorders
Nephrolithiasis	1/508 (0.2%)
Renal failure	1/508 (0.2%)
Renal failure chronic	1/508 (0.2%)
Reproductive system and breast disorders
Ovarian cyst torsion	1/508 (0.2%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/508 (0.4%)
Interstitial lung disease	6/508 (1.2%)
Pulmonary embolism	1/508 (0.2%)
Organising pneumonia	1/508 (0.2%)
Skin and subcutaneous tissue disorders
Drug eruption	1/508 (0.2%)
Skin ulcer	1/508 (0.2%)
Vascular disorders
Aortic rupture	1/508 (0.2%)
Other (Not Including Serious) Adverse Events
	Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection
	Affected / at Risk (%)	# Events
Total	211/508 (41.5%)
Blood and lymphatic system disorders
Anaemia	5/508 (1%)
Disseminated intravascular coagulation	1/508 (0.2%)
Iron deficiency anaemia	5/508 (1%)
Lymphadenopathy	1/508 (0.2%)
Pancytopenia	1/508 (0.2%)
Splenic lesion	1/508 (0.2%)
Cardiac disorders
Acute myocardial infarction	1/508 (0.2%)
Cardiac failure	1/508 (0.2%)
Myocardial infarction	1/508 (0.2%)
Ear and labyrinth disorders
Vertigo	1/508 (0.2%)
Endocrine disorders
Hypothyroidism	1/508 (0.2%)
Eye disorders
Conjunctivitis allergic	1/508 (0.2%)
Gastrointestinal disorders
Abdominal discomfort	1/508 (0.2%)
Abdominal pain upper	2/508 (0.4%)
Constipation	2/508 (0.4%)
Diarrhoea	1/508 (0.2%)
Dry mouth	1/508 (0.2%)
Enterocolitis	1/508 (0.2%)
Gastric ulcer	2/508 (0.4%)
Gastritis	1/508 (0.2%)
Gastrooesophageal reflux disease	1/508 (0.2%)
Gingival swelling	1/508 (0.2%)
Nausea	2/508 (0.4%)
Pancreatitis acute	1/508 (0.2%)
Parotid gland enlargement	1/508 (0.2%)
Periodontal disease	1/508 (0.2%)
Stomatitis	1/508 (0.2%)
Hypoaesthesia oral	1/508 (0.2%)
Diverticular perforation	1/508 (0.2%)
General disorders
Chest discomfort	1/508 (0.2%)
Chills	1/508 (0.2%)
Influenza like illness	1/508 (0.2%)
Injection site erythema	9/508 (1.8%)
Injection site pruritus	1/508 (0.2%)
Injection site rash	3/508 (0.6%)
Injection site reaction	1/508 (0.2%)
Pyrexia	4/508 (0.8%)
Abasia	1/508 (0.2%)
Injection site swelling	1/508 (0.2%)
Deformity	1/508 (0.2%)
Hepatobiliary disorders
Chronic hepatitis	1/508 (0.2%)
Hepatic function abnormal	26/508 (5.1%)
Liver disorder	5/508 (1%)
Non-alcoholic steatohepatitis	1/508 (0.2%)
Immune system disorders
Amyloidosis	1/508 (0.2%)
Sarcoidosis	1/508 (0.2%)
Seasonal allergy	1/508 (0.2%)
Infections and infestations
Acute tonsillitis	1/508 (0.2%)
Atypical pneumonia	1/508 (0.2%)
Bronchitis	21/508 (4.1%)
Bronchopneumonia	3/508 (0.6%)
Cellulitis	4/508 (0.8%)
Chronic sinusitis	1/508 (0.2%)
Clostridium difficile colitis	1/508 (0.2%)
Conjunctivitis	1/508 (0.2%)
Cystitis	2/508 (0.4%)
Epstein-Barr virus infection	1/508 (0.2%)
Erysipelas	1/508 (0.2%)
Gastroenteritis	2/508 (0.4%)
Herpes zoster	9/508 (1.8%)
Impetigo	1/508 (0.2%)
Influenza	1/508 (0.2%)
Listeriosis	1/508 (0.2%)
Lung abscess	1/508 (0.2%)
Meningitis	1/508 (0.2%)
Nasopharyngitis	4/508 (0.8%)
Otitis media	1/508 (0.2%)
Periodontitis	1/508 (0.2%)
Peritonitis	1/508 (0.2%)
Pharyngitis	6/508 (1.2%)
Pneumonia	10/508 (2%)
Pneumonia haemophilus	1/508 (0.2%)
Pneumonia mycoplasmal	1/508 (0.2%)
Pneumonia pneumococcal	1/508 (0.2%)
Pneumonia streptococcal	1/508 (0.2%)
Pulmonary mycosis	1/508 (0.2%)
Pyelonephritis	1/508 (0.2%)
Pyelonephritis acute	1/508 (0.2%)
Sepsis	2/508 (0.4%)
Sinusitis	1/508 (0.2%)
Skin infection	2/508 (0.4%)
Subcutaneous abscess	1/508 (0.2%)
Tinea pedis	1/508 (0.2%)
Tonsillitis	1/508 (0.2%)
Upper respiratory tract infection	1/508 (0.2%)
Urinary tract infection	5/508 (1%)
Arthritis bacterial	1/508 (0.2%)
Enteritis infectious	3/508 (0.6%)
Pneumonia bacterial	4/508 (0.8%)
Atypical mycobacterial infection	1/508 (0.2%)
Purulence	2/508 (0.4%)
Oral herpes	4/508 (0.8%)
Tinea manuum	1/508 (0.2%)
Pneumonia cryptococcal	1/508 (0.2%)
Gastroenteritis norovirus	1/508 (0.2%)
Injury, poisoning and procedural complications
Arthropod sting	1/508 (0.2%)
Chillblains	1/508 (0.2%)
Femoral neck fracture	1/508 (0.2%)
Foot fracture	1/508 (0.2%)
Fracture	1/508 (0.2%)
Frostbite	1/508 (0.2%)
Radius fracture	1/508 (0.2%)
Spinal compression fracture	7/508 (1.4%)
Subdural haematoma	1/508 (0.2%)
Tibia fracture	1/508 (0.2%)
Ulna fracture	1/508 (0.2%)
Contusion	1/508 (0.2%)
Lower limb fracture	1/508 (0.2%)
Pubis fracture	1/508 (0.2%)
Investigations
Alanine aminotransferase increased	1/508 (0.2%)
Aspartate aminotransferase increased	1/508 (0.2%)
Blood creatinine increased	2/508 (0.4%)
C-reactive protein increased	1/508 (0.2%)
Eosinophil count increased	1/508 (0.2%)
Liver function test abnormal	3/508 (0.6%)
Platelet count decreased	3/508 (0.6%)
White blood cell count decreased	3/508 (0.6%)
Blood beta-D-glucan increased	2/508 (0.4%)
Computerised tomogram thorax abnormal	1/508 (0.2%)
Hepatic enzyme increased	3/508 (0.6%)
Cell marker increased	3/508 (0.6%)
Metabolism and nutrition disorders
Diabetes mellitus	3/508 (0.6%)
Hypercholesterolaemia	1/508 (0.2%)
Hyperuricaemia	1/508 (0.2%)
Hyponatraemia	1/508 (0.2%)
Decreased appetite	2/508 (0.4%)
Hyperlipidaemia	2/508 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/508 (0.4%)
Arthritis	2/508 (0.4%)
Back pain	2/508 (0.4%)
Lumbar spinal stenosis	4/508 (0.8%)
Osteoporosis	1/508 (0.2%)
Rheumatoid arthritis	6/508 (1.2%)
Spinal column stenosis	1/508 (0.2%)
Spinal osteoarthritis	2/508 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	2/508 (0.4%)
Gastric cancer	1/508 (0.2%)
Neuroendocrine carcinoma of the skin	1/508 (0.2%)
Lung cancer metastatic	1/508 (0.2%)
Lung neoplasm malignant	2/508 (0.4%)
Prostate cancer	1/508 (0.2%)
Nervous system disorders
Cerebral infarction	3/508 (0.6%)
Diabetic neuropathy	1/508 (0.2%)
Dizziness	1/508 (0.2%)
Dyslalia	1/508 (0.2%)
Headache	2/508 (0.4%)
Hypoaesthesia	1/508 (0.2%)
Migraine	1/508 (0.2%)
VIIth nerve paralysis	1/508 (0.2%)
Psychiatric disorders
Insomnia	2/508 (0.4%)
Anxiety disorder	1/508 (0.2%)
Renal and urinary disorders
Nephrolithiasis	1/508 (0.2%)
Nephrotic syndrome	1/508 (0.2%)
Neurogenic bladder	1/508 (0.2%)
Renal failure	1/508 (0.2%)
Renal failure chronic	1/508 (0.2%)
Renal impairment	1/508 (0.2%)
Reproductive system and breast disorders
Ovarian cyst torsion	1/508 (0.2%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/508 (0.4%)
Cough	3/508 (0.6%)
Dyspnoea	1/508 (0.2%)
Emphysema	1/508 (0.2%)
Interstitial lung disease	8/508 (1.6%)
Pleural effusion	1/508 (0.2%)
Productive cough	2/508 (0.4%)
Pulmonary embolism	1/508 (0.2%)
Rhinitis allergic	1/508 (0.2%)
Rhinorrhoea	1/508 (0.2%)
Upper respiratory tract inflammation	20/508 (3.9%)
Organising pneumonia	1/508 (0.2%)
Skin and subcutaneous tissue disorders
Dermatitis contact	1/508 (0.2%)
Drug eruption	2/508 (0.4%)
Eczema	4/508 (0.8%)
Erythema nodosum	1/508 (0.2%)
Pruritus	4/508 (0.8%)
Rash	10/508 (2%)
Rash erythematous	1/508 (0.2%)
Rash pruritic	2/508 (0.4%)
Skin ulcer	2/508 (0.4%)
Urticaria	6/508 (1.2%)
Vascular disorders
Hypertension	4/508 (0.8%)
Aortic rupture	1/508 (0.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.