Onasemnogene Abeparvovec Administration via Peripherally Inserted Central Catheter: A Case Report.

Onasemnogene abeparvovec (OA) is the approved intravenous gene therapy for the treatment of spinal muscular atrophy (SMA). A functional copy of the human SMN1 gene was inserted into the target motor neuron cells via a viral vector, AAV9. In clinical trials, OA was infused through a peripheral venous catheter, and no data are available on central catheter use. Recently, we had a case where OA was administered directly into the right atrium via a peripherally inserted central catheter (PICC) instead of a peripheral line, as recommended. The patient was a female child aged 4 months, diagnosed as SMA type I. For practical reasons, a dose of OA according to the weight of the patient (1.1 × 1014 vectorial genomes/kg) was administered via PICC in 1 h, as the product information recommends. The drug was well tolerated, with no hypersensitivity reactions or initial elevation of transaminases or other adverse effects. To our knowledge, this is the first case reported where OA was administered via a central line. This type of administration is not contraindicated, but it is not specifically contemplated or recommended. It is unknown whether central line administration could have any implications for transduction efficiency and immunogenicity. Future studies should clarify these aspects, as each gene therapy has a specific optimal dose recorded that depends on the site and route of administration of the drug, the AAV variant and the transgene.

Serum Adalimumab Levels Predict Successful Remission and Safe Deintensification in Inflammatory Bowel Disease Patients in Clinical Practice.

BACKGROUND: Little is known about the association between the pharmacokinetic features of adalimumab (ADL) and disease outcome in patients with inflammatory bowel disease (IBD). AIMS: To assess the association between random serum ADL levels and clinical or biochemical remission with clinical decision making in daily practice according to these levels; and to determine the cutoff value for successful dose reduction in patients with IBD treated with ADL. METHODS: We conducted a prospective observational study of patients with IBD who received long-term maintenance therapy with ADL. RESULTS: Data were available for 157 serum samples from 87 patients. Serum ADL levels were associated with clinical remission: median 9.2 versus 6.0 µg/mL for patients with Crohn's disease with active disease (P = 0.009) and 14.4 versus 5.2 µg/mL in patients with ulcerative colitis with active disease (P = 0.002). Serum ADL levels were 9.2 µg/mL for patients with a normal C-reactive protein value (<5 mg/L) and 5.2 µg/mL for patients with a high C-reactive protein value (P = 0.002). ADL levels were significantly associated with normal fecal calprotectin value (<80 ng/g) (10.8 versus 7.6 µg/mL, respectively, P = 0.038). Serum ADL levels were significantly associated with successful deintensification, over a 6-month period of clinical follow-up, compared with the group in which doses remained unchanged (area under the curve 0.88; 95% confidence interval, 0.81-0.95; P < 0.001), with a cutoff value for successful deintensification of 12.2 µg/mL. CONCLUSIONS: Higher ADA levels were significantly associated with clinical and biochemical remission. Our results, which were obtained under conditions of daily clinical practice, suggest that an ADL cutoff of 12.2 µg/mL could be appropriate for successful dose reduction in patients with IBD treated with ADL.

Fetal exposure to 3,4-diaminopyridine in a pregnant woman with congenital myasthenia syndrome.

OBJECTIVE: To report a case of fetal exposure to pyridostigmine and 3,4-diaminopyridine (3,4-DAP) in a pregnant woman with congenital myasthenia syndrome (CMS). CASE SUMMARY: A 31-year-old woman with postsynaptic CMS, not genetically characterized, was being treated with pyridostigmine and 3,4-DAP. She decided to become pregnant, despite having been informed about the paucity of available information on the possible risks of these drugs for the fetus. The dose of pyridostigmine remained stable throughout the pregnancy (60 mg every 8 h), and the 3,4-DAP dose was adjusted according to the patient's level of fatigue (20 mg/day, with occasional additional doses of 5 mg). At 25 weeks' gestation, ultrasonography confirmed the presence of only one umbilical artery. The results of other tests were normal. At 38 weeks' gestation, a healthy male neonate was born. His APGAR scores were 9 and 10 at 1 and 5 minutes, respectively. Five months later, the infant was healthy and his pediatric progress had been uneventful. DISCUSSION: It was difficult to find information about the possible congenital defects related to the use of 3,4-DAP because it is a rarely used drug. This case attracted our interest because it is an uncommon disease, and we found no reports on the use of 3,4-DAP during pregnancy. To our knowledge, as of this writing, this is the first published report of the use of 3,4-DAP during pregnancy. CONCLUSIONS: A successful pregnancy with a healthy infant was achieved after fetal exposure to 3,4-DAP and pyridostigmine.