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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
  Hide Participant Flow

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 
Overall Participants Analyzed 
[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 
[1] Maternal Age at Estimated Due Date
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 [1] 
[Units: Participants]
     
 134   69   203 
 145   67   212 
 59   19   78 
 23   6   29 
 7   3   10 
Missing   2   0   2 
[1] Based on four-factor Hollingshead categories incorporating maternal and paternal education and occupation; highest socioeconomic status category = 1; lowest socioeconomic status category = 5.
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]
     
 265   117   382 
 73   30   103 
 22   11   33 
≥ 3   10   6   16 
Previous Elective Terminations 
[Units: Participants]
     
 314   150   464 
 49   12   61 
 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 [1] 
[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 
[1] Participants could have more than one comorbidity
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 [1] 
[Units: Years]
Mean (Standard Deviation)
 9.8  (7.9)   10.0  (9.1)   9.9  (8.3) 
[1] 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.
Prednisone and/or Systemic Oral Corticosteroid 
[Units: Participants]
     
Yes   163   65   228 
No   207   99   306 
Disease Severity Score - RA [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 0.5  (0.6)   0.6  (0.6)   0.5  (0.6) 
[1]

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.

Disease Severity Score - PsO [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 2.0  (1.5)   1.9  (1.1)   1.9  (1.4) 
[1] Maternal rating of overall severity of psoriasis measured using Global Assessment of Psoriasis, possible score 0-5 with higher score indicating more severe disease.
Exposed to Etanercept [1] 
[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] 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