ABSTRACT
BACKGROUND & AIMS: Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. AIMS: evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria. METHODS: Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n = 48) or placebo (n = 46) for 6 months (double-blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open-label extension (continuous givosiran, n = 47/48; placebo crossover, n = 46/46). Endpoints included annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events. RESULTS: Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double-blind period, 0.0 in open-label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double-blind period) and 0.0 (open-label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long-term givosiran led to sustained lowering of delta-aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double-blind period. CONCLUSIONS: Long-term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life.
Subject(s)
Porphyria, Acute Intermittent , Porphyrias, Hepatic , Acetylgalactosamine/analogs & derivatives , Humans , Porphyria, Acute Intermittent/chemically induced , Porphyria, Acute Intermittent/drug therapy , Porphyrias, Hepatic/chemically induced , Porphyrias, Hepatic/drug therapy , Pyrrolidines , Quality of LifeSubject(s)
Hydrochlorothiazide , Purpura , Humans , Hydrochlorothiazide/adverse effects , Capillaries , Sunlight , Purpura/etiologyABSTRACT
BACKGROUND: Intralesional injection of Candida antigen appears to be an effective alternative for the treatment of warts. AIM: To determine the efficacy and safety of this treatment. METHODS: We retrospectively reviewed records of all children who received intralesional injection of Candida antigen at our center from January 2008 to July 2013. RESULTS: From a total of 220 patients, 156 (70.9%) had a complete response, 37 (16.8%) had a partial response, and 27 (12.2%) had no improvement. An average of 2.73 treatments was needed. Forty-seven of the patients with more than one wart (21.3%) also noted at least partial resolution of untreated warts at distant sites. Twenty-seven of the 47 patients (57.4%) had complete resolution. All treated patients experienced some discomfort at the time of the injection, but no serious side effects were reported. DISCUSSION: We report our results using this approach in a large group of children. CONCLUSION: Intralesional injection of Candida antigen is an effective and safe therapy for children with multiple and recalcitrant cutaneous warts.