Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors-A retrospective analysis.

INTRODUCTION: Immune tolerance induction (ITI) is the gold standard for eradication of factor VIII inhibitors in severe haemophilia A; however, it usually requires treatment for extended periods with associated high burden on patients and healthcare resources. AIM: Review outcomes of ITI with recombinant factor VIII Fc fusion protein (rFVIIIFc) in patients with severe haemophilia A and high-titre inhibitors. METHODS: Multicentre retrospective chart review of severe haemophilia A patients treated with rFVIIIFc for ITI. RESULTS: Of 19 patients, 7 were first-time ITI and 12 were rescue ITI. Of 7 first-time patients, 6 had at least 1 high-risk feature for ITI failure. Four of 7 first-time patients were tolerized in a median of 7.8 months. The remaining 3 patients continue on rFVIIIFc ITI. Of 12 rescue patients, 7 initially achieved a negative Bethesda titre (≤0.6) in a median of 3.3 months, 1 had a decrease in Bethesda titre and continues on rFVIIIFc ITI and 4 have not demonstrated a decrease in Bethesda titre. Of these 4, 3 continue on rFVIIIFc ITI and 1 switched to bypass therapy alone. Two initially responsive patients transitioned to other factors due to recurrence. Overall, 16 of 19 patients remain on rFVIIIFc (prophylaxis or ITI). For those still undergoing ITI, longer follow-up is needed to determine final outcomes. No adverse events reported. CONCLUSIONS: Recombinant factor VIII Fc fusion protein demonstrated rapid time to tolerization in high-risk first-time ITI patients. For rescue ITI, rFVIIIFc showed therapeutic benefit in some patients who previously failed ITI with other products. These findings highlight the need to further evaluate the use of rFVIIIFc for ITI.

An observational study of glycemic control in canagliflozin treated patients.

OBJECTIVE: To evaluate changes in glycemic control following the initial canagliflozin pharmacy claim in a real-world population. RESEARCH DESIGN AND METHODS: A retrospective cohort analysis of adult patients with type 2 diabetes mellitus (T2DM) was conducted using 2013 medical, pharmacy and laboratory claims from the Inovalon MORE 2 Registry. Patients with T2DM aged ≥18 years with ≥60 days of canagliflozin supply and HbA1c test results within 120 days before and ≥60 days after initial canagliflozin claim (defined as index date) were included. The differences between HbA1c levels pre- and post-index were assessed. Changes pre- and post-index in Healthcare Effectiveness Data and Information Set (HEDIS) glycemic control criteria of HbA1c <7% and <8% and poor control of HbA1c >9% were evaluated. Subgroup analyses of patients with HbA1c >7% at baseline and patients aged ≥65 were also conducted. RESULTS: Among the 268 patients meeting the study criteria, mean HbA1c pre-index was 8.3% and post-index was 7.6%; the mean reduction in HbA1c pre-post index was 0.7% (95% CI: 0.6%, 0.9%). The proportions of patients meeting the HEDIS glycemic control measures (HbA1c <7%, <8% and poor control of >9%) improved and was significantly different pre- and post-index (all p < 0.001). Of the patients with an HbA1c >7% prior to index (81% of the cohort; mean pre-index HbA1c = 8.8%), HbA1c was reduced by 0.9% (95% CI: 0.8%, 1.1%). The aged ≥65 subgroup consisted of 15% of the cohort, with a pre-index HbA1c of 8.3%. The mean reduction in HbA1c test results pre- and post-canagliflozin index was 0.6% (95% CI: 0.4%, 0.9%). This analysis did not adjust for changes in antihyperglycemic agents during the study period. CONCLUSION: Patients with T2DM were observed to have improved glycemic control following initial canagliflozin pharmacy claim as measured by HbA1c change and attainment of specific glycemic control criteria.