Organization of Teratology Information Services (OTIS) Autoimmune Diseases in Pregnancy Project

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00116272
First received: June 28, 2005
Last updated: August 19, 2015
Last verified: August 2015
Results First Received: May 29, 2015  
Study Type: Observational
Study Design: Observational Model: Cohort
Condition: Pregnancy
Intervention: Drug: Etanercept

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Participants were recruited concurrently from callers to Organization of Teratology Information Specialists (OTIS) centers, from health care providers and through direct to consumer marketing efforts.

A third cohort of historical controls including 296 women was also included in the study but are not included in the results of this report.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The first participant was recruited in April, 2005 and recruitment continued through March 19, 2012.

Reporting Groups
  Description
Etanercept-Exposed Pregnant women with a current diagnosis of rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis (AS), psoriatic arthritis (PsoA) or psoriasis (PsO) who used etanercept in the first trimester of pregnancy for any length of time.
Diseased Controls Pregnant women with a current diagnosis of RA, JRA, AS, PsA, or PsO who did not use etanercept or any tumor necrosis factor (TNF) antagonist during pregnancy.

Participant Flow:   Overall Study
    Etanercept-Exposed     Diseased Controls  
STARTED     370     164  
COMPLETED     359 [1]   158 [1]
NOT COMPLETED     11     6  
Lost to Follow-up                 11                 6  
[1] Indicates participants with a known outcome of pregnancy



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Etanercept-Exposed Pregnant women with a current diagnosis of rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis (AS), psoriatic arthritis (PsoA) or psoriasis (PsO) who used etanercept in the first trimester of pregnancy for any length of time.
Diseased Controls Pregnant women with a current diagnosis of RA, JRA, AS, PsA, or PsO who did not use etanercept or any tumor necrosis factor (TNF) antagonist during pregnancy.
Total Total of all reporting groups

Baseline Measures
    Etanercept-Exposed     Diseased Controls     Total  
Number of Participants  
[units: participants]
  370     164     534  
Age, Customized [1]
[units: participants]
     
< 25 years     21     7     28  
25 - 29 years     81     34     115  
30 - 34 years     132     48     180  
> 34 years     136     75     211  
Gender  
[units: participants]
     
Female     370     164     534  
Male     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
Non-Hispanic White     292     138     430  
Black     14     3     17  
Hispanic     42     13     55  
Asian/Pacific Islander     18     6     24  
Native American     3     4     7  
Other     1     0     1  
Maternal Education  
[units: participants]
     
< 12 years     9     4     13  
12 - 15 years     118     42     160  
> 15 years     243     118     361  
Hollingshead Socioeconomic Category [2]
[units: participants]
     
1     134     69     203  
2     145     67     212  
3     59     19     78  
4     23     6     29  
5     7     3     10  
Missing     2     0     2  
Pre-pregnancy Height  
[units: cm]
Mean (Standard Deviation)
  164.7  (7.1)     166.7  (7.0)     165.3  (7.1)  
Pre-pregnancy Body Weight  
[units: kg]
Mean (Standard Deviation)
  70.2  (18.14)     68.3  (16.5)     69.6  (17.8)  
Gravidity Category  
[units: participants]
     
1 pregnancy     135     62     197  
2 -3 pregnancies     163     78     241  
4 -5 pregnancies     60     21     81  
≥ 6 pregnancies     12     3     15  
Parity Category  
[units: participants]
     
0 births     193     88     281  
1 -2 births     153     69     222  
3 - 4 births     22     7     29  
≥ 5 births     2     0     2  
Previous Spontaneous Abortion  
[units: participants]
     
0     265     117     382  
1     73     30     103  
2     22     11     33  
≥ 3     10     6     16  
Previous Elective Terminations  
[units: participants]
     
0     314     150     464  
1     49     12     61  
2     5     1     6  
≥ 3     2     1     3  
Previous Preterm Delivery  
[units: participants]
     
Yes     37     6     43  
No     333     158     491  
Any Previous Child with Birth Defect  
[units: participants]
     
Yes     20     8     28  
No     350     156     506  
In Vitro Fertilization (IVF) with This Pregnancy  
[units: participants]
     
Yes     27     5     32  
No     343     159     502  
Gestational Age at Time of Enrollment  
[units: participants]
     
< 13 weeks     196     84     280  
13 - 19.9 weeks     99     58     157  
≥ 20 weeks     75     22     97  
Referral Source Category  
[units: participants]
     
Sponsor     37     1     38  
Health-care Professional (HCP)     185     53     238  
Internet     65     27     92  
Patient Support Group     0     4     4  
OTIS Member Service     29     69     98  
Other     53     10     63  
Missing     1     0     1  
Geographic Area of Residence  
[units: participants]
     
United States     338     136     474  
Canada     31     27     58  
Missing     1     1     2  
Maternal Comorbidities [3]
[units: participants]
     
Thyroid Disease     45     23     68  
Asthma     48     33     81  
Other Autoimmune Disease     43     17     60  
Antidepressant Medication Use in Any Trimester     28     14     42  
Pre-gestational Hypertension     19     10     29  
Preeclampsia     11     8     19  
Other Psychiatric Conditions     64     32     96  
Infections     274     114     388  
Prenatal Multivitamin or Folic Acid Supplements  
[units: participants]
     
Began Prior to Conception     217     114     331  
Post-conception Only     148     50     198  
Not Taken at All     5     0     5  
Alcohol Use During Pregnancy  
[units: participants]
     
Yes     177     80     257  
No     193     84     277  
Tobacco Use During Pregnancy  
[units: participants]
     
Yes     40     17     57  
No     330     147     477  
Major Known or Suspected Human Teratogens  
[units: participants]
     
Yes     14     11     25  
No     356     153     509  
Intended Pregnancy  
[units: participants]
     
Yes     264     123     387  
No     106     41     147  
Primary Disease (RA, JRA, PsA or AS)  
[units: participants]
     
Yes     311     117     428  
No     59     47     106  
Duration of Disease [4]
[units: years]
Mean (Standard Deviation)
  9.8  (7.9)     10.0  (9.1)     9.9  (8.3)  
Prednisone and/or Systemic Oral Corticosteroid  
[units: participants]
     
Yes     163     65     228  
No     207     99     306  
Disease Severity Score - RA [5]
[units: units on a scale]
Mean (Standard Deviation)
  0.5  (0.6)     0.6  (0.6)     0.5  (0.6)  
Disease Severity Score - PsO [6]
[units: units on a scale]
Mean (Standard Deviation)
  2.0  (1.5)     1.9  (1.1)     1.9  (1.4)  
Exposed to Etanercept [7]
[units: participants]
     
First Trimester     344     0     344  
Last Menstrual Period to Date of Conception     8     0     8  
2nd and/or 3rd Trimester Only     13     0     13  
Started Prior to DOC, End Date Unavailable     5     0     5  
[1] Maternal Age at Estimated Due Date
[2] Based on four-factor Hollingshead categories incorporating maternal and paternal education and occupation; highest socioeconomic status category = 1; lowest socioeconomic status category = 5.
[3] Participants could have more than one comorbidity
[4] Year was known, but month and date were not known for all cases, therefore Jan 1 of the year of diagnosis through the 1st day of the last menstrual period for the index pregnancy was used to calculate duration of disease. In cases where the woman had multiple study diseases, the earliest known year of the “primary disease” diagnosis was used to calculate duration. Five participants in the Etanercept-Exposed Group were missing year of diagnosis.
[5]

RA1 disease severity score expressed as the Health Assessment Questionnaire-Disability Index (HAQ-DI) summary score; possible score ranges from 0-3 with higher score representing higher severity/disability.

RA1 disease severity score at intake missing for 2 participants in the Etanercept-Exposed Group and 1 participant in the Diseased Controls Group.

[6] Maternal rating of overall severity of psoriasis measured using Global Assessment of Psoriasis, possible score 0-5 with higher score indicating more severe disease.
[7] the first trimester of pregnancy is defined as the period between the estimated date of conception (DOC) to the 11th week post-conception. The date of conception is defined as 14 days prior to the next expected menstrual period.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Infants With Major Birth Defects in Pregnancies Ending With Live-born Infants   [ Time Frame: From birth through 1 year of age ]

2.  Primary:   Percentage of Infants With Major Birth Defects in All Pregnancies   [ Time Frame: From birth through 1 year of age ]

3.  Secondary:   Percentage of Infants With Any 3 or More Minor Birth Defects   [ Time Frame: From birth through 1 year of age ]

4.  Secondary:   Percentage of Infants With a Specific Pattern of Any 3 or More Minor Birth Defects   [ Time Frame: From birth through 1 year of age ]

5.  Secondary:   Percentage of Pregnancies Ending in Spontaneous Abortion   [ Time Frame: 9 months ]

6.  Secondary:   Percentage of Participants With Pre-term Delivery   [ Time Frame: 9 months ]

7.  Secondary:   Gestational Age at Delivery (GAD) of Live Births   [ Time Frame: At birth ]

8.  Secondary:   Birth Weight Among Full Term Infants   [ Time Frame: At birth ]

9.  Secondary:   Birth Length Among Full Term Infants   [ Time Frame: At birth ]

10.  Secondary:   Birth Head Circumference Among Full Term Infants   [ Time Frame: At birth ]

11.  Secondary:   Percentage of Infants With Small for Gestational Age Birth Weight   [ Time Frame: At birth ]

12.  Secondary:   Percentage of Infants With Small for Gestational Age Birth Length   [ Time Frame: At birth ]

13.  Secondary:   Percentage of Infants With Small for Gestational Age Birth Head Circumference   [ Time Frame: At birth ]

14.  Secondary:   Postnatal Weight Percentile at One Year   [ Time Frame: 1 year after birth ]

15.  Secondary:   Postnatal Length Percentile at One Year   [ Time Frame: 1 year after birth ]

16.  Secondary:   Postnatal Head Circumference Percentile at One Year   [ Time Frame: 1 year after birth ]

17.  Secondary:   Percentage of Infants at One Year of Age With Small for Gestational Age Weight   [ Time Frame: 1 year after birth ]

18.  Secondary:   Percentage of Infants at One Year of Age With Small for Gestational Age Length   [ Time Frame: 1 year after birth ]

19.  Secondary:   Percentage of Infants at One Year of Age With Small for Gestational Age Head Circumference   [ Time Frame: 1 year after birth ]

20.  Secondary:   Percentage of Infants With Reported Serious or Opportunistic Infections Through One Year   [ Time Frame: From birth to 1 year ]

21.  Secondary:   Percentage of Infants Diagnosed With Any Malignancy Through One Year of Age   [ Time Frame: From birth to 1 year ]

22.  Secondary:   Percentage of Infants With Abnormal Results on Ages and Stages Questionnaire (ASQ)   [ Time Frame: 1 year after birth ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436



Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00116272     History of Changes
Obsolete Identifiers: NCT01017016
Other Study ID Numbers: 20040246
Study First Received: June 28, 2005
Results First Received: May 29, 2015
Last Updated: August 19, 2015
Health Authority: United States: Food and Drug Administration