Delayed-Release Dimethyl Fumarate and Pregnancy: Preclinical Studies and Pregnancy Outcomes from Clinical Trials and Postmarketing Experience (P7.238)
Bibliographic record
Abstract
OBJECTIVE: Present data from animal reproductive toxicology studies and outcomes of pregnancies occurring during the delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) clinical development program and postmarketing experience. BACKGROUND: Women of childbearing age comprise a large proportion of the MS population. It is important to evaluate effects of DMF exposure on pregnancy. DESIGN/METHODS: Reproductive and developmental toxicology was evaluated in rats and rabbits. As of 26 March 2014, clinical studies included 2,898 MS patients, 320 psoriasis patients, 101 rheumatoid arthritis patients, and 813 healthy volunteers; subjects were required to use reliable contraception and immediately discontinue drug in the event of pregnancy. Outcomes as of June 30, 2014 are reported for pregnancies in clinical trials and postmarketing experience. RESULTS: There was no evidence of impaired fertility in rats or teratogenicity in rats and rabbits given DMF. Pregnancy outcomes are known for 40 of 45 pregnancies in subjects receiving DMF in clinical trials: 27 live births (60[percnt]), 3 spontaneous abortions (7[percnt]), and 10 elective terminations (22[percnt]). Information is pending for 4 subjects and 1 was lost to follow-up. The incidence of spontaneous abortion was consistent with the expected rate of early pregnancy loss in the general population (12-22[percnt]). A total of 135 pregnancies were reported in the postmarketing setting (104 spontaneous reports and 31 solicited reports); pregnancy is ongoing in 103 cases. There were 10 live births, 13 spontaneous abortions, and 5 elective terminations; 2 patients were lost to follow-up. There was one reported fetal abnormality (not considered associated with DMF). CONCLUSIONS: Based on available evidence with known gestational exposure limited to the first trimester, DMF was not associated with increased risk of fetal abnormalities or adverse pregnancy outcomes. Outcomes are being monitored through spontaneous reports in the postmarketing setting and a pregnancy registry. Study Supported by: Biogen Idec
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.010 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".