Introduction Prospectively collected, real‐world data on bleeds, haemophilic treatment and safety outcomes in persons with haemophilia A (PwHA) with factor VIII (FVIII) inhibitors are limited. A prospective, global, multi‐centre, non‐interventional study (NIS; NCT02476942) collected detailed real‐world data in PwHA treated per local routine clinical practice. Aim To characterize bleeding rates, haemophilic treatment practices, prophylaxis adherence and adverse events (AEs) in adult/adolescent PwHA with inhibitors in the NIS. Methods Participants aged ≥12 years with congenital haemophilia A/documented high‐titre FVIII inhibitor history were enrolled. Participants remained on their usual treatment; no interventions were applied. Results Overall, 103 PwHA with inhibitors enrolled, (median [range] age 31 [12‐75] years) and were monitored for median (range) 26.0 (4.1‐69.6) weeks. In the episodic (n = 75) and prophylactic (n = 28) treatment groups, respectively, 1244 and 325 bleeds were reported, and 528 (42.4%) and 104 (32.0%) were not treated; annualized bleeding rates (ABRs; 95% confidence interval) were 18.6 (15.2‐22.8) and 14.9 (10.5‐21.2) for treated bleeds, and 32.7 (27.3‐39.1) and 25.0 (18.4‐34.0) for all bleeds. Coagulation products used included activated prothrombin complex concentrate (aPCC) and/or recombinant activated FVII. Among participants prescribed aPCC prophylaxis, 35.0% adhered to both prescribed frequency of aPCC administration and prescribed dose. Serious AEs of haemarthrosis and muscle haemorrhage were reported; most common AEs were arthralgia, viral upper respiratory tract infection and pyrexia. Conclusions ABRs (treated bleeds and all bleeds) remain high on standard treatment; this prospective NIS demonstrates the need for more effective treatments for PwHA with inhibitors to reduce/prevent bleeds, with potential to improve prophylaxis adherence and further improve outcomes.

Introduction Real‐world data (RWD) on health‐related outcomes in persons with haemophilia A (PwHA) provide insights into patient needs and can guide clinical study design. A global, prospective, non‐interventional study (NIS; NCT02476942) collected detailed RWD on bleeding outcomes, health‐related quality of life (HRQoL) and health status in PwHA treated per local routine clinical practice. Aim To report HRQoL and health status in the adult/adolescent PwHA with inhibitors cohort in the NIS. Methods This cohort enrolled PwHA aged ≥12 years with high‐titre factor VIII inhibitor history. Participants remained on their usual treatment (no protocol‐specified interventions). Health‐related outcomes: Haemophilia Quality of Life Questionnaire for Adults (Haem‐A‐QoL), Haemophilia‐specific Quality of Life Questionnaire for Children Short Form (Haemo‐QoL SF), EuroQol 5‐Dimensions 5‐Levels (EQ‐5D‐5L) index utility score (IUS) and visual analogue scale (EQ‐VAS). Results One hundred three participants were enrolled on episodic (n = 75) or prophylactic treatment (n = 28); median (range) age, 31 (12‐75) years; median (range) observation time, 26 (4‐70) weeks. Haem‐A‐QoL scores indicated impairments in HRQoL aspects; comparable between episodic/prophylactic regimens and relatively consistent over time. Haemo‐QoL SF scores with both regimens varied over time, and appeared poorer with episodic than prophylactic treatment. IUS and EQ‐VAS were comparable between regimens, stable over time and lower on bleeding days. Mean proportions of missed work and school days were 16% and 23%, respectively; mean (standard deviation) number of days hospitalized was 3.2 (8.8) (comparable between groups). Conclusions These RWD demonstrate that PwHA with inhibitors have impaired HRQoL, despite standard treatment, and that more effective treatment options are needed.

Young adults ages 18 to 25 have the highest percentage (5%) of cannabis use disorder (CUD) among all age groups, and are the least likely to receive treatment compared with other age groups. Because this population is in need of creative approaches for treatment engagement, we tested Peer Network Counseling-txt (PNC-txt), a 4-week, automated text-delivered cannabis treatment that focuses on close peer relations with 96 treatment seeking young adults. Participants meeting CUD criteria were randomized to PNC-txt, or assessment only control condition and followed for 3-months. At 3-months, the PNC-txt group reduced number of heavy cannabis-use days and relationship problems due to cannabis use compared with controls. Subgroup analyses were conducted with cases having more and fewer CUD symptoms than the full sample. For cases with fewer symptoms, but not for those with more, PNC-txt reduced past 30-day use, urges to use, memory problems, and relationship problems due to cannabis use compared with controls. Treatment satisfaction data from the full sample indicated that participants thought the intervention texts helped them reduce or manage their cannabis use and increased their understanding of the negative relational effects associated with ongoing cannabis use. Findings provide evidence of the efficacy of PNC-txt in treating CUD in young adults, support clinically targeting peer relations, and suggest that PNC-txt may be most helpful for those with mild to moderate CUD severity.

Introduction: Coagulation factor VIII (FVIII) deficiency in hemophilia A (HA) patients (pts) results in spontaneous bleeding events, secondary arthropathy and diminished quality of life (QoL). FVIII replacement agents, the current standard of care, may require several infusions to treat bleeding events and infusions 2-3 times a week are needed for prevention of bleeding events due to relatively short half-lives. A major challenge of current therapies is development of anti-FVIII alloantibodies (inhibitors), which occur in 15-30% of HA pts, diminish effectiveness of FVIII replacement and are associated with significant morbidity and reduced QoL. Options for pts with inhibitors are limited. Bypassing agents to prevent/treat bleeding events, and immune tolerance induction to eliminate inhibitors, require frequent dosing, are not available in all countries, and have suboptimal efficacy. Thus, a high unmet need exists for safe, more effective and less burdensome options for pts with inhibitors. Emicizumab (ACE910), a bispecific monoclonal antibody in development for the management of HA, binds to FIXa and FX to mimic FVIII cofactor function and may be able to address current treatment needs. Real world data (RWD) collected from HA pts are considered of high importance for the emicizumab clinical development program, providing the possibility of intra-patient comparison for those who may be subsequently eligible to participate in a pivotal emicizumab Phase 3 study (NCT02622321). This non-interventional study (NIS) aims to prospectively collect detailed, high-quality data on bleeding events and safety outcomes in HA pts treated according to local routine clinical practice. In the first cohort (Cohort A), data from adult/adolescents with inhibitors were collected. Methods: This prospective NIS (NCT02476942) was approved by local Ethics review groups, and all pts and/or legal guardians signed informed consent/assent prior to study entry. In Cohort A, eligible pts were ≥12 years old and had congenital HA of any severity; documented history of high-titer FVIII inhibitors (≥5 Bethesda Units/mL); documented treatment with bypassing agents for ≥6 months; and, ≥6 or ≥2 bleeds in the last 6 months on episodic or prophylactic treatment, respectively. Primary objective was to characterize the number of bleeding events over time. Bleeding/bypassing agent data were collected through a bleed and medication questionnaire (BMQ) developed by the Sponsor, as no standard questionnaire is available. BMQ was completed by the pt/legal guardian via an electronic handheld device. Demographic data and medical history were collected from pts' medical records on an electronic Case Report Form. Throughout the study, investigators recorded adverse events (AEs), concomitant medication, and routine laboratory assessment data. At least monthly interactions of pts/legal guardian with a professional from their treatment center were requested to confirm self-reported bleed/medication information. Results: 103 HA pts with inhibitors (75 on episodic and 28 on prophylactic regimens with bypassing agents) from 33 centers and 12 countries were enrolled in Cohort A. As of 7/21/16, 54 pts had rolled over to the emicizumab Phase 3 study in adults/adolescents with inhibitors. The following Cohort A data will be presented: pt demographics/characteristics; global distribution of pts by country; summary of hemophilia medical history, concomitant medications and surgeries; pts' self-reported information on bleeding events and treatment (all, and by episodic and prophylactic treatment), including bleeding rates, types and locations, reason for coagulation product use, product type used, dose; and, safety. Conclusion: The NIS will provide high quality documentation of bleeding events and safety outcomes in adult/adolescent HA pts with inhibitors treated with bypassing agents according to local clinical practice. For those participating in the ongoing Phase 3 emicizumab study, these data will provide the opportunity to perform robust intra-patient comparisons of prospectively collected bleeding event/medication data before and during emicizumab treatment. This is the first report of prospective RWD being collected for use as a valid historical control for a pivotal Phase 3 study in HA pts with inhibitors, and a novel and unique approach to bolster data reported in the clinical development of emicizumab. Disclosures Mahlangu: Bayer: Research Funding, Speakers Bureau; Biogen: Consultancy, Research Funding, Speakers Bureau; CSL: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding; Amgen: Speakers Bureau; Biotest: Speakers Bureau; Baxalta: Consultancy. Callaghan:Grifols: Honoraria; Bayer: Honoraria; Baxalta: Honoraria, Research Funding; Roche: Honoraria, Research Funding; CSL Behring: Honoraria; Biogen: Honoraria. Shima:F. Hoffmann-La Roche Ltd.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Sysmex Corporation: Patents & Royalties, Research Funding. Santagostino:Bayer: Consultancy; Grifols: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Octapharma: Consultancy; CSL Behring: Consultancy; Baxalta: Consultancy; Pfizer: Consultancy; Biogen Idec: Consultancy; Sobi: Consultancy; Roche: Consultancy. Lehle:Roche: Employment. Uguen:Roche: Employment. Hirst:F. Hoffmann La-Roche Ltd: Employment; AstraZeneca: Other: Previous employment . Recht:Novo Nordisk: Consultancy, Research Funding; Biogen Idec: Research Funding; Baxalta: Research Funding; Kedrion: Consultancy. Kruse-Jarres:Pfizer: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Baxalta: Consultancy, Honoraria; Bayer: Consultancy, Honoraria.

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