Very-early-onset inflammatory bowel disease (VEO-IBD), representing cases diagnosed before age 6 years, is increasing in prevalence. Although VEO-IBD often presents as severe, treatment-resistant disease requiring biologic agents, studies showing the effectiveness of biologics, such as ustekinumab (UST) and vedolizumab (VDZ), remain limited. We retrospectively analyzed patients with VEO-IBD treated for at least a year from 13 institutions in Japan, evaluating clinical course including effectiveness of biologics, such as infliximab (IFX), adalimumab (ADL), UST, and VDZ. Patients with monogenic IBD were excluded. Steroid-free clinical remission (SFCR) and treatment persistence were assessed separately for first-line and for second-line or subsequent biologic therapies. We studied 101 VEO-IBD patients (56
OBJECTIVE:Evaluate long-term efficacy, safety, and tolerability of once-weekly somapacitan, a long-acting growth hormone (GH) derivative, in children born small for gestational age (SGA) with short stature, including after switching from daily GH. DESIGN:REAL5 (NCT03878446) is a global, randomized, open-label, controlled phase 2 study comprising a 26-week main phase, 26-week extension I, and an ongoing 4-year extension II. METHODS:Sixty-two children born SGA with short stature were recruited at 38 clinics across 12 countries and randomized (1:1:1:1:1) to somapacitan (0.16, 0.20, or 0.24 mg/kg/week) or daily GH (0.035 or 0.067 mg/kg/day) until week 52 (inclusive main phase and extension I). Sixty participants entered extension II. Forty-eight participants switched to somapacitan 0.24 mg/kg/week from cohorts randomized to daily GH or lower somapacitan doses. Fifty-five children completed 208 weeks of treatment. Novel safety and efficacy results from week 52 to 208 are presented here. RESULTS:Across all treatment arms, continuous increases in height standard deviation scores were observed from week 52 to week 208, including after switch to somapacitan 0.24 mg/kg/week. The safety and tolerability profile for somapacitan 0.24 mg/kg/week was similar to the well-established safety and tolerability profile for daily GH in SGA. Patient preference questionnaire results indicate that most respondents (87%) prefer somapacitan over daily GH. Most respondents (80%) answered that they expect to be more adherent to treatment with somapacitan. CONCLUSIONS:These results support long-term continuous efficacy, safety, and tolerability of GH therapy with somapacitan 0.24 mg/kg/week for up to 4 years in children born SGA, including after switching from daily GH. CLINICALTRIALS.GOV:NCT03878446.
BACKGROUND:Although macrolide antibiotics are an effective first-line treatment for pertussis, the global emergence and spread of macrolide-resistant Bordetella pertussis (MRBP) presents a significant threat to antimicrobial treatment strategies. However, the current status of MRBP in Japan remains unclear due to the lack of a surveillance system. This study aimed to highlight the emergence and clinical impact of MRBP in Osaka, Japan. METHODS:We retrospectively reviewed cases of patients with pertussis whose B. pertussis strains were analyzed at the Osaka Institute of Public Health between August 2024 and January 2025. Information on the patients' clinical characteristics, therapeutic interventions, antimicrobial susceptibility, and molecular analysis of B. pertussis strains was collected. During the study period, eight B. pertussis strains were analyzed. RESULTS:Seven of the eight (87.5 %) B. pertussis strains were macrolide resistant. All of the MRBP strains were highly resistant to macrolide antibiotics and carried the A2047G mutation in domain V of the 23S rRNA gene. Seven of the patients were pediatric; four of whom had not been fully vaccinated due to their young age. One unvaccinated 31-day-old infant experienced clinical and microbiological treatment failure following macrolide administration, resulting in severe hypoxia and lymphocytosis. CONCLUSIONS:This descriptive analysis of recent pertussis cases in Osaka identified a high proportion of macrolide-resistant strains among the analyzed cases. Notably, one infant developed severe disease despite macrolide treatment. These findings support the urgent need for nationwide surveillance of macrolide resistance in Japan and the establishment of an appropriate initial antimicrobial strategy for suspected MRBP.
