Ipsen is a French pharmaceutical company headquartered in Paris, France.[self-published source] It is specialized in oncology, neuroscience and rare diseases. It is publicly traded on the Euronext Paris as part of the SBF 120 index (2005).Ipsen, founded by Henri Beaufour in 1929, has 5,700 employees worldwide, and markets 20 drugs in 115 countries. The Beaufour family owns 57% of its shares and 73% of its voting rights,[self-published source] and two of its members, Anne Beaufour and Henri Beaufour, sit on its board of directors.
Lack of head-to-head comparative safety and efficacy data for abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) represented an important gap for informed spasticity management. This study compared the safety and efficacy of aboBoNT-A and onaBoNT-A for upper limb spasticity (ULS). DIRECTION (NCT04936542), a phase IV, randomized, double-blind, crossover study, involved 72 sites. Patients stratified by botulinum toxin A status (naïve/non-naïve) were randomized (1:1) to aboBoNT-A 900U followed by onaBoNT-A 360U (one cycle each), or vice versa. Muscles (wrist/finger flexors, biceps brachii) were injected with a fixed volume, using instrument-guided injection techniques. Participants fulfilling retreatment criteria received a second cycle at Week 12; otherwise, they were reassessed every 4 weeks (to Week 24) until requiring retreatment. Primary analyses tested non-inferiority based on treatment-emergent adverse events (TEAEs) from injection to Week 12 using a 5 Spasticity of the upper limb presents as muscle and limb stiffness that affects the arm and/or hand. It happens when parts of the brain or spinal cord that control movement are damaged. Spasticity can be painful and can make daily activities challenging. Some people with upper limb spasticity receive botulinum toxin A (BoNT-A) injections to help relax the affected muscles. BoNT-A injections work for a period, but retreatment is required when the effects start to wear off. AbobotulinumtoxinA and onabotulinumtoxinA are different types of BoNT-A. DIRECTION is the first-ever spasticity study to compare abobotulinumtoxinA and onabotulinumtoxinA directly in people with upper limb spasticity. It involved 464 people living with spasticity across the USA, France, and Canada. The study population had an average age of 57 years, two-thirds were male, and most had spasticity because of a stroke. The study found that, over the 12 weeks after BoNT-A treatment, similar numbers of patients had side-effects to abobotulinumtoxinA and onabotulinumtoxinA. In addition, it took longer for symptoms to return after treatment with abobotulinumtoxinA (99 days) compared with onabotulinumtoxinA (96 days). Longer BoNT-A treatment duration can reduce the number of days that people with upper limb spasticity have to live with symptoms before their next injection. More symptom-free days could reduce the need for patients and their caregivers to seek additional care and could reduce their overall treatment burden. These findings provide new information to help healthcare professionals make decisions about BoNT-A treatment to achieve the best outcomes for their patients with arm/hand spasticity.
Closed-source large language models (LLMs), such as ChatGPT and Gemini, are increasingly consulted for medical advice, yet their explanations may appear plausible while failing to reflect the model's underlying reasoning process. This gap poses serious risks as patients and clinicians may trust coherent but misleading explanations. We conduct a systematic black-box evaluation of faithfulness in medical reasoning among three widely used closed-source LLMs. Our study consists of three perturbation-based probes: (1) causal ablation, testing whether stated chain-of-thought (CoT) reasoning causally influences predictions; (2) positional bias, examining whether models create post-hoc justifications for answers driven by input positioning; and (3) hint injection, testing susceptibility to external suggestions. We complement these quantitative probes with a small-scale human evaluation of model responses to patient-style medical queries to examine concordance between physician assessments of explanation faithfulness and layperson perceptions of trustworthiness. We find that CoT reasoning steps often do not causally drive predictions, and models readily incorporate external hints without acknowledgment. In contrast, positional biases showed minimal impact in this setting. These results underscore that faithfulness, not just accuracy, must be central in evaluating LLMs for medicine, to ensure both public protection and safe clinical deployment.
CONTEXT:The Global Increlex® Growth Forum Database (IGFD) Registry monitors real-world effectiveness and safety of recombinant human IGF-1 (rhIGF-1; Increlex® [mecasermin]) treatment in children and adolescents with severe growth failure due to severe primary IGF-I deficiency (SPIGFD). OBJECTIVE:To report characteristics, effectiveness, and safety data from patients receiving rhIGF-1 treatment who achieved near-adult height (NAH), and determine factors that predict height gain to NAH. METHODS:Descriptive analyses of patients included in the Global IGFD Registry (NCT00903110) who achieved NAH are reported for the overall population, treatment-naïve prepubertal (NPP) patients, and patients with Laron syndrome. Linear regression analyses of height gain to NAH are also reported. RESULTS:One hundred and two patients enrolled in the Global IGFD Registry achieved NAH at data cut-off (April 20, 2023). Mean age at rhIGF-1 treatment initiation was 11.8 years; median treatment duration was 3.9 years. Mean (SD) height SD score (HtSDS) gain from rhIGF-1 initiation to NAH was 0.9 (1.1). In NPP patients, mean (SD) HtSDS gain was 1.4 (1.0). Almost half of NPP patients reached NAH within the normal range. Despite improved height in patients with Laron syndrome, only 10.5% reached NAH within the normal range; 3 patients with Laron syndrome were NPP. Treatment naivety was predictive of height gain in the overall NAH population. Safety data aligned with previous reports. CONCLUSION:In a real-world setting, despite patients with SPIGFD initiating rhIGF-1 treatment at a relatively advanced age, rhIGF-1 treatment resulted in improved NAH. The greatest improvements in height outcomes were observed in NPP patients. TRIAL REGISTRATION:NCT00903110.
