Delayed−Release Dimethyl Fumarate and Pregnancy: Preclinical Studies and Pregnancy Outcomes Reported During the Clinical Development Program (S24.006)
Bibliographic record
Abstract
OBJECTIVE: Present preclinical data from animal reproductive toxicology studies and the outcomes of pregnancies occuring during the delayed-release dimethyl fumarate (DMF) clinical development program. BACKGROUND: No formal studies of delayed-release DMF were conducted in pregnant women, but pregnancies have occurred during the clinical development program. DESIGN/METHODS: Reproductive and developmental toxicology was evaluated in rats and rabbits. Delayed-release DMF clinical studies included 2,665 MS patients, 320 psoriasis patients, 101 rheumatoid arthritis patients, and 338 healthy volunteers. Subjects were required to use reliable contraception and immediately discontinue drug in the event of pregnancy. Pregnancy outcomes as of January 2, 2013 (data cutoff) are reported in this abstract; outcomes as of January, 2014 will be presented. RESULTS: There was no evidence of impaired fertility in rats or teratogenicity in rats and rabbits given dimethyl fumarate at doses that caused reductions in maternal weight gain. As of January 2, 2013, 38 pregnancies in delayed-release DMF recipients (37 MS patients, 1 healthy volunteer) and 14 pregnancies in placebo recipients were reported in clinical studies. Information is pending for three delayed-release DMF recipients and one was lost to follow-up; hence, results for delayed-release DMF are reported for the 34 pregnancies with known outcomes. In patients exposed to delayed-release DMF, 22 live births (64.7%), 3 spontaneous abortions (8.8%), and 9 elective terminations (26.5%) were reported. In placebo recipients, 9 live births (64.3%), 3 spontaneous abortions (21.4%), and 2 elective terminations (14.3%) were reported. No fetal abnormalities were reported. The incidence of spontaneous abortion was consistent with the expected rate of early pregnancy loss in the general population (12-22%). CONCLUSIONS: Based on the available data, no increased risk of fetal abnormalities or adverse pregnancy outcomes associated with gestational exposure to delayed-release DMF during the first trimester has been observed. Further data will be collected through a pregnancy registry. Study supported by: Biogen Idec, Inc.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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".