Efficacy and safety of @entity2816 for the treatment of severe XXXX in @entity1884 : results of a non-randomised, single-centre, phase 2 study.

@entity1 @entity417 @entity548 @entity1415 @entity4 @entity2816 @entity34536 @entity1884 @entity2817 @entity74 @entity1142
BACKGROUND: @entity1884 is a @entity74 that leads to multiregional @entity2817 . Severe @entity1415 is the most common presentation, frequently leading to severe @entity417 . Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results. We aimed to assess the efficacy of @entity2816 for the reduction of @entity1415 in @entity1 with @entity1884 that is refractory to standard therapy. METHODS: We recruited @entity1 aged 17 years or older with @entity1884 who had severe @entity1415 refractory to minimally invasive surgical procedures into an open-label, phase 2, non-randomised, single-centre study at IRCCS Policlinico San Matteo Foundation (Pavia, Italy). We gave @entity1 @entity2816 at a starting dose of 50 mg/day orally. If they had no response, we increased the @entity2816 dose by 50 mg/day increments every 4 weeks, until a response was seen, up to a maximum dose of 200 mg/day. After @entity1 had achieved a response, they continued treatment for 8-16 additional weeks. The primary endpoint was the efficacy of @entity2816 measured as the percentage of @entity1 who had reductions of at least one grade in the frequency, intensity, or duration of @entity1415 . We followed up @entity1 each month to assess @entity1415 severity score and transfusion need, and any adverse events were reported. We included all @entity1 who received any study drug and who participated in at least one post-baseline assessment in the primary efficacy population. The safety population consisted of all @entity1 who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01485224. FINDINGS: Between @entity34536 , 2011, and May 12, 2014, we enrolled 31 @entity1 . Median follow-up was 15  9 months (IQR 10  1-22  3). Three (10%, 95% CI 2-26) @entity1 had a complete response, with @entity548 stopped, 28 (90%, 95% CI 74-98) @entity1 had partial responses. Overall, all 31 (100%, 89-100) @entity1 responded to therapy with a significant decrease in all @entity1415 parameters (p<0  0001 for frequency, intensity, and duration). A response was achieved by 25 (81%) @entity1 at 50 mg/day of @entity2816 , five (16%) @entity1 at 100 mg/day, and one (3%) @entity1 at 150 mg/day. @entity1 had only non-serious, grade 1 adverse effects, the most common of which were @entity1142 (21 @entity1 ), drowsiness (six @entity1 ), and peripheral @entity4 (eight @entity1 ). One @entity1 died a month after the end of treatment, but this was not deemed to be related to treatment. INTERPRETATION: Low-dose @entity2816 seems to be safe and effective for the reduction of @entity1415 in @entity1 with @entity1884 . Our findings should be validated by further studies with larger @entity1 populations, longer follow-up, and that also assess the benefit for quality of life. FUNDING: Telethon Foundation.
