Anakinra to Treat Patients With Neonatal Onset Multisystem Inflammatory Disease

• ClinicalTrials.gov Identifier: NCT00069329
• Recruitment Status: Terminated
• First Posted: September 23, 2003
• Results First Posted: December 1, 2016
• Last Update Posted: December 1, 2016
• Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Nervous System Malformations; Arthropathy, Neurogenic; Urticaria; Papilledema
• Intervention: Drug: anakinra
• Enrollment: 43

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	NOMID
Arm/Group Description	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Period Title: Overall Study
Started	43
Completed	41
Not Completed	2

Baseline Characteristics

Arm/Group Title		NOMID
Arm/Group Description		Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Baseline Participants		43
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	43 participants
	<=18 years	36 83.7%
	Between 18 and 65 years	7 16.3%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	43 participants
	Female	25 58.1%
	Male	18 41.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	43 participants
	Hispanic or Latino	8 18.6%
	Not Hispanic or Latino	33 76.7%
	Unknown or Not Reported	2 4.7%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	43 participants
	American Indian or Alaska Native	0 0.0%
	Asian	4 9.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	1 2.3%
	White	29 67.4%
	More than one race	1 2.3%
	Unknown or Not Reported	8 18.6%

Outcome Measures

1. Primary Outcome

Title	Diary Symptom Sum Score (DSSS) (Fever, Rash, Joint Pain, Vomiting, and Headaches)
Description	"The severity of the main symptoms of the disease were scored on a scale from 0 (no symptoms) to 4 (highest severity) on a daily basis using a diary. Five key symptoms were included in the primary variable DSSS: fever, headache, rash, joint pain, and vomiting. Each of the diary variables was evaluated as a mean value for a period preceding the visits. The baseline value was the mean value of the 5-30 last days before the first dose of Kineret. For the subsequent visits, the mean value of the last 30 days with data before each visit was used as the response variable."
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg/day per injection were made as frequently as every 2 weeks to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.75741904 (0.08370955)

2. Primary Outcome

Title	Diary Symptom Sum Score (DSSS) (Fever, Rash, Joint Pain, Vomiting, and Headaches)
Description	"The severity of the main symptoms of the disease were scored on a scale from 0 (no symptoms) to 4 (highest severity) on a daily basis using a diary. Five key symptoms were included in the primary variable DSSS: fever, headache, rash, joint pain, and vomiting. Each of the diary variables was evaluated as a mean value for a period preceding the visits. The baseline value was the mean value of the 5-30 last days before the first dose of Kineret. For the subsequent visits, the mean value of the last 30 days with data before each visit was used as the response variable."
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 4.5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.08704545 (0.02470396)

3. Primary Outcome

Title	Diary Symptom Sum Score (DSSS) (Fever, Rash, Joint Pain, Vomiting, and Headaches)
Description	"The severity of the main symptoms of the disease were scored on a scale from 0 (no symptoms) to 4 (highest severity) on a daily basis using a diary. Five key symptoms were included in the primary variable DSSS: fever, headache, rash, joint pain, and vomiting. Each of the diary variables was evaluated as a mean value for a period preceding the visits. The baseline value was the mean value of the 5-30 last days before the first dose of Kineret. For the subsequent visits, the mean value of the last 30 days with data before each visit was used as the response variable."
Time Frame	60 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 20 patients who completed their 5 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.10768421 (0.04158048)

4. Primary Outcome

Title	Patient / Parent Global Score of Overall Disease Activity
Description	Visual analog assessment of how arthritis affects the patient as rated by the patient themselves or parent. Measured on scale from very well (0 mm) to very poor (100 mm).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg/day per injection were made as frequently as every 2 weeks to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: units on a scale
	40.22381 (4.6242215)

5. Primary Outcome

Title	Patient / Parent Global Score of Overall Disease Activity
Description	Visual analog assessment of how arthritis affects the patient as rated by the patient themselves or parent. Measured on scale from very well (0 mm) to very poor (100 mm).
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 4.5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: units on a scale
	8.1923077 (2.7291978)

6. Primary Outcome

Title	Patient / Parent Global Score of Overall Disease Activity
Description	Visual analog assessment of how arthritis affects the patient as rated by the patient themselves or parent. Measured on scale from very well (0 mm) to very poor (100 mm).
Time Frame	60 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 20 patients who completed their 5 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: units on a scale
	11.1 (3.6322025)

7. Primary Outcome

Title	Parent /Patient Pain Rating
Description	Visual analog assessment of how much pain the patient experienced in past week due to illness as rated by the patient themselves or parent. Measured on scale from no pain (0 mm) to very severe pain (100 mm).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg/day per injection were made as frequently as every 2 weeks to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: units on a scale
	41.22381 (4.9988185)

8. Primary Outcome

Title	Parent /Patient Pain Rating
Description	Visual analog assessment of how much pain the patient experienced in past week due to illness as rated by the patient themselves or parent. Measured on scale from no pain (0 mm) to very severe pain (100 mm).
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 4.5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: units on a scale
	8.9423077 (2.892075)

9. Primary Outcome

Title	Parent /Patient Pain Rating
Description	Visual Analog assessment of how much pain the patient experienced in past week due to illness as rated by the patient themselves or parent. Measured on scale from no pain (0 mm) to very severe pain (100 mm).
Time Frame	60 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 20 patients who completed their 5 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: units on a scale
	9.8525 (3.1635745)

10. Primary Outcome

Title	Childhood Health Assessment Questionnaire (CHAQ)
Description	Patient self-assessment (or parent assessment) for how illness affects ability to function in daily life. Includes overall score, overall pain rating, overall global evaluation, subcategories for dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. Measured on scale of 0-3 from 'Without any difficulty' (0) to 'Unable to do' (3).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg/day per injection were made as frequently as every 2 weeks to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: units on a scale
	1.1051429 (0.21122155)

11. Primary Outcome

Title	Childhood Health Assessment Questionnaire (CHAQ)
Description	Patient self-assessment (or parent assessment) for how illness affects ability to function in daily life. Includes overall score, overall pain rating, overall global evaluation, subcategories for dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities.Measured on scale of 0-3 from 'Without any difficulty' (0) to 'Unable to do' (3).
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 4.5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.66346154 (0.15898857)

12. Primary Outcome

Title	Childhood Health Assessment Questionnaire (CHAQ)
Description	Patient self-assessment (or parent assessment) for how illness affects ability to function in daily life. Includes overall score, overall pain rating, overall global evaluation, subcategories for dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. Measured on scale of 0-3 from 'Without any difficulty' (0) to 'Unable to do' (3).
Time Frame	60 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 20 patients who completed their 5 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.590625 (0.180202)

13. Primary Outcome

Title	Serum Amyloid A (SAA) Measurement
Description	Serum Amyloid A is an inflammatory marker for NOMID measured using Rapid Automated Enzyme Immunoassay. Normal SAA values were defined as ≤ 10 mg/liter.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg/day per injection were made as frequently as every 2 weeks to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: mg/liter
	220.28077 (38.27684)

14. Primary Outcome

Title	Serum Amyloid A (SAA) Measurement
Description	Serum Amyloid A is an inflammatory marker for NOMID measured using Rapid Automated Enzyme Immunoassay. Normal SAA values were defined as ≤ 10 mg/liter.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 4.5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: mg/liter
	22.333333 (7.5122284)

15. Primary Outcome

Title	Serum Amyloid A (SAA) Measurement
Description	Serum Amyloid A is an inflammatory marker for NOMID measured using Rapid Automated Enzyme Immunoassay. Normal SAA values were defined as ≤ 10 mg/liter.
Time Frame	60 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 20 patients who completed their 5 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: mg/liter
	21.3125 (11.586169)

16. Primary Outcome

Title	C-reactive Protein (CRP) Measurement
Description	C-reactive protein (CRP) is an inflammatory marker for NOMID. Systemic inflammatory remission was defined as a normal CRP level (≤0.5mg/dl). Analyzed at the NIH Clinical Center Laboratory.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg/day per injection were made as frequently as every 2 weeks to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: mg/dl
	57.703077 (7.2213655)

17. Primary Outcome

Title	C-reactive Protein (CRP) Measurement
Description	C-reactive protein (CRP) is an inflammatory marker for NOMID. Systemic inflammatory remission was defined as a normal CRP level (≤0.5mg/dl). Analyzed at the NIH Clinical Center Laboratory.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 4.5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: mg/dl
	8.7511538 (2.2674947)

18. Primary Outcome

Title	C-reactive Protein (CRP) Measurement
Description	C-reactive protein (CRP) is an inflammatory marker for NOMID. Systemic inflammatory remission was defined as a normal CRP level (≤0.5mg/dl). Analyzed at the NIH Clinical Center Laboratory.
Time Frame	60 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 20 patients who completed their 5 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: mg/dl
	6.0585 (2.3462251)

19. Primary Outcome

Title	Erythrocyte Sedimentation Rate (ESR) Measurement
Description	Erythrocyte Sedimentation Rate (ESR) is an inflammatory marker for NOMID. Normal ESR values are defined as ≤ 25 mm/hour. Analyzed at the NIH Clinical Center Laboratory.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg/day per injection were made as frequently as every 2 weeks to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: mm/hour
	56.923077 (6.3138244)

20. Primary Outcome

Title	Erythrocyte Sedimentation Rate (ESR) Measurement
Description	Erythrocyte Sedimentation Rate (ESR) is an inflammatory marker for NOMID. Normal ESR values are defined as ≤ 25 mm/hour. Analyzed at the NIH Clinical Center Laboratory.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 4.5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	26
Mean (Standard Deviation); Unit of Measure: mm/hour
	11.576923 (1.3222045)

21. Primary Outcome

Title	Erythrocyte Sedimentation Rate (ESR) Measurement
Description	Erythrocyte Sedimentation Rate (ESR) is an inflammatory marker for NOMID. Normal ESR values are defined as ≤ 25 mm/hour. Analyzed at the NIH Clinical Center Laboratory.
Time Frame	60 months

Outcome Measure Data

Analysis Population Description

Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg per injection were made as frequently as every 2 weeks up to 5 mg/kg/day to achieve laboratory and organ inflammation remission. Data reported is on 20 patients who completed their 5 year assessment.

Arm/Group Title	NOMID
Arm/Group Description:	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: mm/hour
	11.35 (2.4355103)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	NOMID
Arm/Group Description	Patients who met the criteria for NOMID and treated with escalating doses of anakinra 1-5 mg/kg/day to achieve laboratory and organ inflammation remission.
All-Cause Mortality
	NOMID
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	NOMID
	Affected / at Risk (%)
Total	18/43 (41.86%)
Cardiac disorders
hospital admission for cardiac catheterization †	1/43 (2.33%)
Eye disorders
Uveitis †	1/43 (2.33%)
Gastrointestinal disorders
diarrhea †	1/43 (2.33%)
Gastritis †	1/43 (2.33%)
vomiting †	1/43 (2.33%)
Immune system disorders
Cytokine release syndrome †	1/43 (2.33%)
Infections and infestations
Acute Tonsillitis/tooth abscess †	1/43 (2.33%)
Appendicitis †	1/43 (2.33%)
Arthritis †	1/43 (2.33%)
Cellulitis Right lower extremity †	1/43 (2.33%)
Left cervical lymphadenitis †	1/43 (2.33%)
Lung infection †	2/43 (4.65%)
Meningitis †	1/43 (2.33%)
Pneumonitis †	1/43 (2.33%)
Right ankle cellulitis †	1/43 (2.33%)
Wound infection †	1/43 (2.33%)
Metabolism and nutrition disorders
Metabolic toxicity †	1/43 (2.33%)
Musculoskeletal and connective tissue disorders
generalized muscle weakness †	1/43 (2.33%)
Pain †	1/43 (2.33%)
Nervous system disorders
Headache †	5/43 (11.63%)
Meningitis †	1/43 (2.33%)
Pain †	1/43 (2.33%)
Seizure †	1/43 (2.33%)
Renal and urinary disorders
Renal calculi †	1/43 (2.33%)
Reproductive system and breast disorders
Double Mastectomy †	1/43 (2.33%)
Low grade focal ductal carcinoma in-situ of left breast †	1/43 (2.33%)
Right breast inflammation post surgery †	1/43 (2.33%)
Right breast scar/fibrotic tissue excised from inplant capsule †	1/43 (2.33%)
Skin and subcutaneous tissue disorders
Hospitalized for Rash †	1/43 (2.33%)
Surgical and medical procedures
Bilateral Capsulectomy with permenant implants †	1/43 (2.33%)
L ureter stent placed †	1/43 (2.33%)
Left renal stent removal †	1/43 (2.33%)
Lithotripsy †	1/43 (2.33%)
Post-Surgery Pneumonia †	1/43 (2.33%)
Suicidal ideation †	1/43 (2.33%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	NOMID
	Affected / at Risk (%)
Total	43/43 (100.00%)
Blood and lymphatic system disorders
bicarbonate †	1/43 (2.33%)
blood / Bone Marrow - Other - elevated Hematocrit †	1/43 (2.33%)
blood / Bone Marrow - Other - eosinophilia †	2/43 (4.65%)
blood / Bone Marrow - Other - low reticulocyte count †	1/43 (2.33%)
Blood bilirubin increased †	1/43 (2.33%)
Bruising †	4/43 (9.30%)
Epistaxis †	4/43 (9.30%)
hemoglobin †	1/43 (2.33%)
Hypomagnesemia †	1/43 (2.33%)
Hyponatremia †	1/43 (2.33%)
Proteinuria †	1/43 (2.33%)
Transient elevation of LFT's †	1/43 (2.33%)
Cardiac disorders
Angiodema Right ring finger †	1/43 (2.33%)
Chest wall pain †	4/43 (9.30%)
Hypertension †	1/43 (2.33%)
Palpitations †	1/43 (2.33%)
Sinus tachycardia †	1/43 (2.33%)
Vasovagal reaction †	2/43 (4.65%)
Ear and labyrinth disorders
ear drainage †	1/43 (2.33%)
ear pain †	1/43 (2.33%)
Hearing impaired †	2/43 (4.65%)
Tinnitus †	1/43 (2.33%)
Endocrine disorders
Hypothyroidism †	1/43 (2.33%)
weight gain †	2/43 (4.65%)
Eye disorders
Conjunctivitis †	16/43 (37.21%)
Dry eye †	1/43 (2.33%)
Eye infection †	1/43 (2.33%)
eye inflammation (left) †	1/43 (2.33%)
Eye pain †	4/43 (9.30%)
eye throbbing †	1/43 (2.33%)
foreign body in eye †	1/43 (2.33%)
Glaucoma †	1/43 (2.33%)
hemmorage in eye †	1/43 (2.33%)
itchy eyes †	1/43 (2.33%)
Nystagmus †	2/43 (4.65%)
Pain in extremity †	1/43 (2.33%)
sty on left eye †	1/43 (2.33%)
vision - eye twitch †	1/43 (2.33%)
Gastrointestinal disorders
Abdominal pain †	7/43 (16.28%)
Alanine aminotransferase increased †	2/43 (4.65%)
Anorexia †	1/43 (2.33%)
Aspartate aminotransferase increased †	1/43 (2.33%)
canker sore †	1/43 (2.33%)
Cold Sore on Gums †	1/43 (2.33%)
Constipation †	4/43 (9.30%)
Diarrhea †	10/43 (23.26%)
Dysphagia †	1/43 (2.33%)
Flatulence †	1/43 (2.33%)
Gastritis †	6/43 (13.95%)
Gastrointestinal pain †	6/43 (13.95%)
Increased Liver Enzymes †	1/43 (2.33%)
Nausea †	6/43 (13.95%)
Uveitis †	1/43 (2.33%)
vomiting †	9/43 (20.93%)
Weight loss †	1/43 (2.33%)
General disorders
Disease Flare †	1/43 (2.33%)
Fatigue †	7/43 (16.28%)
Flare Symptoms (pt had 1 week of no anakinra) †	1/43 (2.33%)
Flare, ran out of anakinra †	1/43 (2.33%)
Insomnia †	7/43 (16.28%)
Irritability †	1/43 (2.33%)
Malaise †	2/43 (4.65%)
NOMID Flare †	1/43 (2.33%)
Immune system disorders
Allergic reaction †	2/43 (4.65%)
Allergic rhinitis †	1/43 (2.33%)
Infections and infestations
Allergic rhinitis †	3/43 (6.98%)
Blastocystis Hominis Infection †	1/43 (2.33%)
bowel abcess †	1/43 (2.33%)
Bronchial infection †	5/43 (11.63%)
Candida on palms and soles of feet bilaterally †	1/43 (2.33%)
C-Diff Recurrence †	1/43 (2.33%)
Chest Infection (?Pneumonia) †	1/43 (2.33%)
Chest wall pain †	1/43 (2.33%)
Chills †	1/43 (2.33%)
Conjunctivitis †	4/43 (9.30%)
Croup †	1/43 (2.33%)
ear drainage †	1/43 (2.33%)
Ear pain †	1/43 (2.33%)
Eczema / Atopic Dermatitis †	1/43 (2.33%)
External ear inflammation †	14/43 (32.56%)
Fever †	16/43 (37.21%)
Flu like symptoms †	15/43 (34.88%)
Folliculitis - L-Groin †	1/43 (2.33%)
G Tube Infection †	1/43 (2.33%)
Gastritis †	7/43 (16.28%)
Gastrointestinal pain †	1/43 (2.33%)
Hand-Foot-Mouth Disease †	1/43 (2.33%)
Headache †	1/43 (2.33%)
Hearing impaired †	2/43 (4.65%)
Hypopyon - Left eye †	1/43 (2.33%)
infected finger †	1/43 (2.33%)
infection without Neutropenia †	1/43 (2.33%)
infection without Neutropenia - (yeast) †	1/43 (2.33%)
infection without Neutropenia - Left arm thrombophlebitis †	1/43 (2.33%)
infection without Neutropenia - tonsillitis with sore throat †	1/43 (2.33%)
infection without Neutropenia (tooth abcess) †	1/43 (2.33%)
itchy †	1/43 (2.33%)
Lice †	1/43 (2.33%)
Lung infection †	3/43 (6.98%)
Mouth Infection †	1/43 (2.33%)
mouth sores †	1/43 (2.33%)
Nasal congestion †	9/43 (20.93%)
Oral Ulcer †	1/43 (2.33%)
Otitis externa †	2/43 (4.65%)
Otitis media †	10/43 (23.26%)
Pharyngitis †	3/43 (6.98%)
Pneumonitis †	1/43 (2.33%)
R ear D/C †	1/43 (2.33%)
Red & burning sensation on bottom of feet †	1/43 (2.33%)
ringworm †	1/43 (2.33%)
Rotaviral Infection †	1/43 (2.33%)
RSV (Resp. Syncytial Virus) †	1/43 (2.33%)
RSV infection †	1/43 (2.33%)
Scalp Lesion (? Tinea capitis) †	1/43 (2.33%)
scarlett fever †	1/43 (2.33%)
Shingles †	1/43 (2.33%)
Sinusitis †	15/43 (34.88%)
Skin infection †	1/43 (2.33%)
sore throat †	10/43 (23.26%)
Strep throat †	2/43 (4.65%)
strep throat (2x) †	1/43 (2.33%)
Stye †	1/43 (2.33%)
Throat infection †	1/43 (2.33%)
Tooth infection (?abscess) †	1/43 (2.33%)
Upper respiratory infection †	19/43 (44.19%)
Urinary tract infection †	4/43 (9.30%)
Urinary tract pain †	5/43 (11.63%)
Viral Illness †	2/43 (4.65%)
Viral Illness Dehydration †	1/43 (2.33%)
Viral Infection †	4/43 (9.30%)
Viral Infection Fever, Lethargy †	1/43 (2.33%)
Vision loss †	1/43 (2.33%)
yeast infection †	1/43 (2.33%)
Injury, poisoning and procedural complications
Auto Accident †	1/43 (2.33%)
Fall †	7/43 (16.28%)
Physical Assault †	1/43 (2.33%)
Investigations
CPK increased †	1/43 (2.33%)
Metabolism and nutrition disorders
Weight gain †	1/43 (2.33%)
Musculoskeletal and connective tissue disorders
Anxiety †	1/43 (2.33%)
Arthralgia †	16/43 (37.21%)
Back pain †	7/43 (16.28%)
Chest wall pain †	1/43 (2.33%)
Conjunctivitis †	1/43 (2.33%)
Dysmenorrhea †	1/43 (2.33%)
Edema limbs †	1/43 (2.33%)
Fatigue †	5/43 (11.63%)
Flu like symptoms †	2/43 (4.65%)
Fracture †	3/43 (6.98%)
Gait disturbance †	4/43 (9.30%)
Malaise †	1/43 (2.33%)
Myalgia †	3/43 (6.98%)
Myositis †	1/43 (2.33%)
Neck pain †	7/43 (16.28%)
Osgood-Schlatter †	1/43 (2.33%)
pain †	6/43 (13.95%)
Pain in extremity †	14/43 (32.56%)
restless leg syndrome †	1/43 (2.33%)
S/P L Knee growth plate fixation/fever thematoma †	1/43 (2.33%)
Nervous system disorders
A.D.D. †	1/43 (2.33%)
Allergic reaction †	1/43 (2.33%)
Anxiety †	1/43 (2.33%)
Blurred vision †	2/43 (4.65%)
carpal tunnel - right †	1/43 (2.33%)
cerebrospinal fluid leakage †	1/43 (2.33%)
Dizziness †	4/43 (9.30%)
External ear pain †	1/43 (2.33%)
Fever †	1/43 (2.33%)
Generalized muscle weakness †	1/43 (2.33%)
Glaucoma †	1/43 (2.33%)
Headache †	23/43 (53.49%)
Hearing impaired †	3/43 (6.98%)
Hoarseness †	1/43 (2.33%)
Nausea †	1/43 (2.33%)
Neck pain †	1/43 (2.33%)
Pain in extremity †	1/43 (2.33%)
Paresthesia of R hand suggestive of carpel tunnel †	1/43 (2.33%)
Saccadic Pursuit Neuropathy - Cranial †	1/43 (2.33%)
Seizure †	1/43 (2.33%)
Uveitis †	1/43 (2.33%)
Vertigo †	3/43 (6.98%)
vomiting †	1/43 (2.33%)
Renal and urinary disorders
Bladder infection †	2/43 (4.65%)
Catheter related infection †	1/43 (2.33%)
Flank pain †	1/43 (2.33%)
glucosuria †	1/43 (2.33%)
Hematuria †	1/43 (2.33%)
Ketonuria †	1/43 (2.33%)
metabolic (elevated BUN) †	1/43 (2.33%)
metabolic / Laboratory - Other - elevated Blood Urea Nitrogen †	1/43 (2.33%)
Proteinuria †	1/43 (2.33%)
Renal calculi †	2/43 (4.65%)
Renal colic †	1/43 (2.33%)
Upper respiratory infection †	2/43 (4.65%)
Urinary incontinence †	1/43 (2.33%)
Urinary tract infection †	3/43 (6.98%)
Urinary tract pain †	2/43 (4.65%)
Reproductive system and breast disorders
Breakthrough bleeding (menstrual) †	1/43 (2.33%)
Phantom pain of breats bilateraly †	1/43 (2.33%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm †	1/43 (2.33%)
Cough †	9/43 (20.93%)
Dyspnea †	2/43 (4.65%)
Gait disturbance †	1/43 (2.33%)
Nasal congestion †	2/43 (4.65%)
Sinusitis †	1/43 (2.33%)
Stridor †	1/43 (2.33%)
Skin and subcutaneous tissue disorders
Allergic reaction †	2/43 (4.65%)
bug bite †	1/43 (2.33%)
cyst on Right cheek †	1/43 (2.33%)
Dry skin †	3/43 (6.98%)
Eczema (contact dermatitis) †	1/43 (2.33%)
eczematous reaction to injection †	1/43 (2.33%)
Erythema Left Foot †	1/43 (2.33%)
eye swollen †	1/43 (2.33%)
fungal rash †	1/43 (2.33%)
hive †	1/43 (2.33%)
hives †	1/43 (2.33%)
Hot/diaphoretic in summer months - rash at beltline †	1/43 (2.33%)
Ingrown toenail †	1/43 (2.33%)
Injection site reaction †	10/43 (23.26%)
Intermittent rash on body †	1/43 (2.33%)
lesion on scrotum †	1/43 (2.33%)
Oral Ulcers †	2/43 (4.65%)
Papulopustular rash †	1/43 (2.33%)
Penile pain †	1/43 (2.33%)
Perineal pain †	1/43 (2.33%)
R. 2nd toenail injury with ingrown nail †	1/43 (2.33%)
Rash †	13/43 (30.23%)
Rash - (contact dermatitis) †	1/43 (2.33%)
Rash - adhesive (IV site) †	1/43 (2.33%)
Rash - Bugbite - R ear †	1/43 (2.33%)
Rash - Lichenified rash on glutial crack †	1/43 (2.33%)
Rash - Reaction to U-bag †	1/43 (2.33%)
Rash (viral infection) †	1/43 (2.33%)
rash / desquamation †	1/43 (2.33%)
Rash arms, trunk, legs †	1/43 (2.33%)
Rash on Arms †	1/43 (2.33%)
Rash on Right Leg †	1/43 (2.33%)
rashes †	1/43 (2.33%)
red cheeks †	1/43 (2.33%)
Red Dots †	1/43 (2.33%)
red dots - rash †	1/43 (2.33%)
Red Dots on Arm †	1/43 (2.33%)
Skin infection †	1/43 (2.33%)
Surgical and medical procedures
Cesarean Section †	1/43 (2.33%)
Dental Surgery Outpatient †	1/43 (2.33%)
Elective L cochlear implant surgery †	1/43 (2.33%)
Elective Osteotomy †	1/43 (2.33%)
Endoscopy to replace G Tube †	1/43 (2.33%)
eye surgery †	1/43 (2.33%)
hand surgery - carpal tunnel †	1/43 (2.33%)
Kidney Stent removal †	1/43 (2.33%)
Lithotripsy/stent removed †	1/43 (2.33%)
Placement of BMT (tubes) †	1/43 (2.33%)
staples in knee (surgery) †	1/43 (2.33%)
Surgery Adenoidectomy, Placement of bilateral myringotomy tubes †	1/43 (2.33%)
surgery for cyst removal †	1/43 (2.33%)
surgery on right knee †	1/43 (2.33%)
surgery on wrist †	1/43 (2.33%)
Tonsillectomy †	1/43 (2.33%)
Ureteral stent for renal calculi - Right kidney †	1/43 (2.33%)
Wisdom Teeth Extraction †	1/43 (2.33%)
Vascular disorders
hypertension †	1/43 (2.33%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

Data reported is on 26 patients who completed their 3 year assessment and 20 of these patients also completed their 5 year assessment.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Goldbach-Mansky, Raphaela
• Organization: National Inst of Arthritis and Musculoskeletal and Skin Diseases
• Phone: +1 301 435 6243
• EMail: goldbacr@mail.nih.gov

Publications:

Feldmann J, Prieur AM, Quartier P, Berquin P, Certain S, Cortis E, Teillac-Hamel D, Fischer A, de Saint Basile G. Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet. 2002 Jul;71(1):198-203. Epub 2002 May 24.

Hashkes PJ, Lovell DJ. Recognition of infantile-onset multisystem inflammatory disease as a unique entity. J Pediatr. 1997 Apr;130(4):513-5.

Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet. 2001 Nov;29(3):301-5.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rodriguez-Smith J, Lin YC, Tsai WL, Kim H, Montealegre-Sanchez G, Chapelle D, Huang Y, Sibley CH, Gadina M, Wesley R, Bielekova B, Goldbach-Mansky R. Cerebrospinal Fluid Cytokines Correlate With Aseptic Meningitis and Blood-Brain Barrier Function in Neonatal-Onset Multisystem Inflammatory Disease: Central Nervous System Biomarkers in Neonatal-Onset Multisystem Inflammatory Disease Correlate With Central Nervous System Inflammation. Arthritis Rheumatol. 2017 Jun;69(6):1325-1336. doi: 10.1002/art.40055. Epub 2017 May 10.

Kullenberg T, Löfqvist M, Leinonen M, Goldbach-Mansky R, Olivecrona H. Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. Rheumatology (Oxford). 2016 Aug;55(8):1499-506. doi: 10.1093/rheumatology/kew208. Epub 2016 May 3.

Chang Z, Spong CY, Jesus AA, Davis MA, Plass N, Stone DL, Chapelle D, Hoffmann P, Kastner DL, Barron K, Goldbach-Mansky RT, Stratton P. Anakinra use during pregnancy in patients with cryopyrin-associated periodic syndromes (CAPS). Arthritis Rheumatol. 2014 Nov;66(11):3227-32.

Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, Zalewski C, Kim HJ, Bishop R, Hill S, Paul SM, Kicker P, Phillips Z, Dolan JG, Widemann B, Jayaprakash N, Pucino F, Stone DL, Chapelle D, Snyder C, Butman JA, Wesley R, Goldbach-Mansky R. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. Arthritis Rheum. 2012 Jul;64(7):2375-86. doi: 10.1002/art.34409.

Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, Kim HJ, Brewer C, Zalewski C, Wiggs E, Hill S, Turner ML, Karp BI, Aksentijevich I, Pucino F, Penzak SR, Haverkamp MH, Stein L, Adams BS, Moore TL, Fuhlbrigge RC, Shaham B, Jarvis JN, O'Neil K, Vehe RK, Beitz LO, Gardner G, Hannan WP, Warren RW, Horn W, Cole JL, Paul SM, Hawkins PN, Pham TH, Snyder C, Wesley RA, Hoffmann SC, Holland SM, Butman JA, Kastner DL. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006 Aug 10;355(6):581-92.

• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) )
• ClinicalTrials.gov Identifier: NCT00069329
• Other Study ID Numbers: 030298; ZIAAR041138-08 ( U.S. NIH Grant/Contract ); 03-AR-0298 ( Other Identifier: NIHCC )
• First Submitted: September 22, 2003
• First Posted: September 23, 2003
• Results First Submitted: May 6, 2016
• Results First Posted: December 1, 2016
• Last Update Posted: December 1, 2016