Examination and Validation of a Patient-Centric Joint Metric: "Problem Joint"; Empirical Evidence from the CHESS US Dataset

Introduction Severe hemophilia (FVIII/FIX level <1%) is characterized by spontaneous hemarthrosis leading to progressive joint deterioration and chronic pain in the affected individual. Unless these recurrent hemarthroses can be prevented, e.g. with the use of prophylactic factor replacement therapy, these patients will develop chronic synovitis, pain, and eventually destruction of the joint. Current metrics such as 'Target joint' and other clinical measures of joint morbidity are prevalent and widely accepted. Measures focused solely on bleeding activity, such as the 'Target joint' metric, are arguably becoming less sensitive as current treatment strategies look to significantly reduce or eradicate joint bleeds, though they maintain clinically relevant and complementary to delivery of comprehensive hemophilia care. Key opinion leaders in the haemophilia field have debated the need for a more patient relevant measure of haemophilia-related joint morbidity. 'Problem Joint' (PJ), which is defined as having chronic joint pain and/or limited range of movement due to compromised joint integrity (chronic synovitis and/or haemophilic arthropathy), with or without persistent bleeding was derived through consensus. The objectives of this working group are to examine the usefulness and validity of the PJ metric. Initial research presented here was used to test the sensitivity of PJ as a patient relevant metric with respect to key outcomes for US haemophilia patients. Methods Data on PJs, as well as demographic, clinical and socio-economic variables was captured within the 'Cost of Haemophilia Across Europe: A Socioeconomic Survey' datasets (CHESS: I, II, Paediatric, and US studies). These data contain a total of 992 paediatric (age 1-17) and 2,437 adults (age 18+) with haemophilia from eight European countries and the US. Statistical analysis explored the association of PJ count and location with respect to two key outcomes: quality of life, as measured by an EQ-5D score, and overall work impairment, measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). Those with current inhibitors were excluded from the analysis, and the US cohort comprised the focus of this initial research into the topic. Results The US cohort contained information on 345 people with haemophilia (PwH) and captured adults only, with a mean age of 35 years. Approximately, 43% of PwH had one or more PJs. Lower body PJs were more prevalent than upper body: 40% had one or more lower body PJs vs. 27% upper body. The majority of PJs were located in the ankles, knees and elbows. The relationship between EQ-5D and number of PJs showed a negative trend (see Figure 1): the average EQ-5D score was: 0.81 for those with zero PJs (N=197); 0.79 for those with one PJ (N=24); 0.70 for two PJs (N=29); 0.68 for three PJs (N=24) and 0.49 for those patients with four of more PJs (N=59). Similarly, an increase in number of PJs meant greater work productivity impairment versus no PJs recorded: 30.08% (N=102) vs. 19.51% (N=137), respectively. Discussion Results from the US cohort found that an increase in the number of PJs was associated with an increasing humanistic burden in PwH. The proposed Problem Joint definition takes a holistic viewpoint and provides a patient relevant perspective. Further work is planned to evaluate the appropriateness of the measure, and test the sensitivity in European and pediatric cohorts. Disclosures Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Rodriguez Santana:HCD Economics: Current Employment. Chowdary:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Shire (Baxalta): Membership on an entity's Board of Directors or advisory committees; Spark: Membership on an entity's Board of Directors or advisory committees; BioMarin: Honoraria; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Freeline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Curtis:Bayer: Consultancy; Novo Nordisk: Consultancy; Patient Reported Outcomes, Burdens and Experiences: Consultancy; USC Hemophilia Utilization Group Study (HUGS): Consultancy. Khair:Haemnet: Membership on an entity's Board of Directors or advisory committees; Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau. Laffan:Shire: Consultancy; LFB: Consultancy; Roche: Consultancy; Sobi: Consultancy; Pfizer: Consultancy; CSL: Consultancy; Pfizer: Speakers Bureau; Bayer: Speakers Bureau; Roche-Chugai: Speakers Bureau; Takeda: Speakers Bureau; Leo-Pharma: Speakers Bureau; Octapharma: Consultancy. McLaughlin:BioMarin: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Roche/Chugai: Speakers Bureau; Takeda: Speakers Bureau. Noone:European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees; Research Investigator PROBE: Research Funding; Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees. O'Mahony:Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees; Freeline: Honoraria; UniQure: Honoraria. Pasi:BioMarin: Consultancy, Honoraria, Other: Grants, personal fees, and nonfinancial support; honoraria as member of scientific advisory boards and symposia; uniQure: Other: Grants and nonfinancial support , Research Funding; ApcinteX: Consultancy, Other: Personal fees ; Octapharma: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia , Speakers Bureau; Novo Nordisk: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia ; Catalyst Biosciences: Consultancy, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Biotest: Consultancy, Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Alnylam (Sanofi): Other: Personal fees and nonfinancial support ; Takeda: Consultancy, Honoraria, Other: Personal fees; honoraria as member of scientific advisory boards and symposia ; Sanofi: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; Sigilon: Research Funding; Tremeau: Research Funding; Sobi: Consultancy, Honoraria, Other; Roche: Honoraria, Other; Pfizer: Other. Skinner:Genentech: Consultancy, Honoraria; Spark Therapeutics: Other, Speakers Bureau; Pfizer: Other, Speakers Bureau; Takeda: Honoraria, Research Funding; uniQure: Research Funding; Biomarin: Consultancy, Research Funding; CSL Behring: Research Funding; Freeline Therapeutics: Research Funding; Novo Nordisk: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Sobi: Research Funding; Bayer: Consultancy, Research Funding. O'Hara:HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy.

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