Teriflunomide Treatment Is Not Associated With Increased Risk of Infections: Pooled Data From the Teriflunomide Development Program (P2.194)
Bibliographic record
Abstract
OBJECTIVE: To characterize infections and opportunistic infections (OIs) during teriflunomide treatment. BACKGROUND: Teriflunomide is a once-daily oral immunomodulator for the treatment of relapsing-remitting multiple sclerosis (RRMS). In clinical studies, teriflunomide has shown beneficial effects on relapse rate and disability progression. By blocking a key mitochondrial enzyme in the de novo pyrimidine pathway, teriflunomide reduces proliferation of activated lymphocytes, potentially limiting their contribution to MS disease activity. DESIGN/METHODS: Data regarding infections, serious infections, and serious OIs were pooled from four placebo-controlled studies: phase 2 (NCT01487096), TEMSO (NCT00134563), TOWER (NCT00751881), and TOPIC (NCT00622700). Patients were randomized and exposed to teriflunomide 14mg (n=1002) or 7mg (n=1045), or placebo (n=997). Pooled data from the aforementioned studies or for up to 12 years in the extensions of the phase 2 (NCT00228163) or TEMSO (NCT00803049) studies (teriflunomide 14mg, n=1134, 7mg, n=1204) are also reviewed. RESULTS: In placebo-controlled studies, duration of treatment exposure and frequency of patients with infections was similar across groups (14mg=1517 patient-years [PYs], 53.4%; 7mg=1561 PYs, 52.9%; placebo=1508 PYs, 52.7%). Rate of infections over time was similar across treatment groups. Serious infections occurred infrequently, with similar incidence across groups (14mg=2.7%; 7mg=2.2%; placebo=2.2%). Five serious OIs were reported in placebo-controlled studies: hepatitis with cytomegalovirus (CMV) and gastrointestinal tuberculosis (14mg); pulmonary tuberculosis (7mg); herpes zoster and hepatitis C with CMV (placebo). One additional serious OI was reported during extension studies (treatment exposure: 14mg=3304 PYs; 7mg=3512 PYs): oral herpes with weakness and walking difficulty leading to hospitalization (7mg; unrelated to teriflunomide per investigator assessment). All patients with serious OIs had white blood cell counts within the normal range prior to start of infection. CONCLUSIONS: The low incidence of serious infections and serious OIs seen in teriflunomide-treated patients did not differ from placebo. Furthermore, there was no notable pattern of OIs. These results demonstrate no increased risk of infection with teriflunomide in clinical trials. Study Supported by: Genzyme, a Sanofi company.
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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 | 0.012 | 0.019 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.015 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
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".