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Gaucher Disease: Overview and Therapeutic Goals. Gaucher Disease: Overview  The most common lysosomal storage disease 1 Incidence: approximately 1 in.

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Presentation on theme: "Gaucher Disease: Overview and Therapeutic Goals. Gaucher Disease: Overview  The most common lysosomal storage disease 1 Incidence: approximately 1 in."— Presentation transcript:

1 Gaucher Disease: Overview and Therapeutic Goals

2 Gaucher Disease: Overview  The most common lysosomal storage disease 1 Incidence: approximately 1 in 40,000 for non-Jewish populations 3  Caused by a deficiency of the enzyme glucocerebrosidase 1,2  The glycolipid glucocerebroside accumulates in lysosomes of macrophages 1,2  Lipid-filled Gaucher cells displace normal cells in 3 Bone marrow Spleen Liver Lungs CNS* * In neuronopathic subtypes only. 1. Grabowski GA. Lancet. 2008;372:1263– Futerman AH, et al. Nat Rev Mol Cell Biol. 2004;5:554– Sidransky E, et al. Emedicine Web site. Accessed February 12, CNS = central nervous system. © 2009 Rector and Visitors of the University of Virginia. Charles E. Hess, MD, and Lindsey Krstic, BA, RN (arrow indicates Gaucher cell)

3 Assessment of Disease Severity and Development of Treatment Goals in Type 1 Gaucher Disease

4 Gaucher Disease: Clinical Signs and Symptoms Grabowski GA. Lancet. 2008;372:1263–1271. Pulmonary involvement Progressive neurologic symptoms* Hepatosplenomegaly Skeletal involvement Thrombocytopenia and anemia * In neuronopathic subtypes only.

5 Assessing Disease Severity DomainAssessmentDisease Severity Score Index Skeletal DomainBMIabsent/minimalmildintermediatesevere Mineral componentabsent/minimalmildintermediatesevere Osteonecrosisnonemedullary infarctionosteonecrosisprosthesis Fractureabsent+ Hematological DomainHemoglobin > 12 g/dL (male) > 11.5 g/dL (female)10–12 g/dL8–9.9 g/dL < 8 g/dL* (*) or need for blood transfusion WBC count> 4 x 10 9 /L2.5–4 x 10 9 /L< 2.5 x 10 9 /L< 1.9 x 10 9 /L Platelet count> 150 x 10 9 /L101–150 x 10 9 /L60–100 x 10 9 /L< 60 x 10 9 /L Bleeding time< 8 min> 8 min Biomarker DomainChitotriosidase< 600 nmol/mL x h 600–4,000 nmol/mL x h 4,001–15,000 nmol/mL x h> 15,000 nmol/mL x h CCL 18< 72 ng/mL72–236 ng/mL237–1,000 ng/mL> 1,000 ng/mL Visceral DomainSpleen no MR/US lesions no splenectomy volume < 5 N volume between 5–9 N splenectomy volume between 10–15 N MR/US lesions volume > 15 N Liver no hepatic disease volume < 1.25 N volume between 1.25–2.5 Nvolume > 2.5 Nhepatic disease Lung DomainPulmonary hypertensionabsentmoderatesevere Respiratory failureabsentmoderatesevere Neurological Domainno signs/symptoms peripheral neuropathy Parkinson’s disease/Parkinsonism Total

6 Therapeutic Goals  Developed by a group of physicians from around the world with clinical expertise in treating Gaucher patients (ICGG)  Areas targeted for treatment goal development Visceral organs  Liver volume  Spleen volume Hematological  Anemia  Thrombocytopenia Pulmonary  Interstitial lung disease  Pulmonary vascular disease  Time frames that are described are based on past experience with alglucerase/imiglucerase  These goals may be useful as benchmarks when evaluating treatment regimens Pastores GM, et al. Semin Hematol. 2004;41(4Suppl 5):4–14. Skeletal pathology  Bone pain/bone crises  Osteonecrosis and subchondral joint collapse  Bone mineral density Growth (pediatric population)  Growth patterns/puberty Functional health and well-being  Normal daily activities

7 Therapeutic Goals: Hepatosplenomegaly Hepatomegaly* Splenomegaly* Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14. PatientsGoal Time Frame All patients  Reduce liver volume to 1–1.5 times normal and maintain All patients  Reduce liver volume by 20–30%  Reduce liver volume by 30–40% Years 1 to 2 Years 3 to 5 PatientsGoalTime Frame All patients  Reduce spleen volume to ≤ 2 to 8 times normal and maintain All patients  Reduce spleen volume by 30–50%  Reduce spleen volume by 50–60% Year 1 Years 2 to 5 All patients  Alleviate symptoms due to splenomegaly: abdominal distension, early satiety, new splenic infarction  Eliminate hypersplenism *Please note regular assessments will be conducted.

8 Therapeutic Goals: Anemia* PatientsGoalTime Frame Adult female patients and children Hb ≥ 11.0 g/dLYears 1 to 2 Male patients > 12 years Hb ≥ 12.0 g/dLYears 1 to 2 All patients  Eliminate blood transfusion  Reduce fatigue  Maintain improved Hb levels Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14. *Please note regular assessments will be conducted.

9 Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14. PatientsGoalTime Frame All patients  Sufficient platelets to reduce bleedingYear 1 Splenectomized patients  Normalization of platelet countsYear 1 Intact spleen Moderate thrombocytopenia (> 60,000–< 120,000/mm 3 ) Severe thrombocytopenia (< 60,000/mm 3 )  Low-normal platelet counts  Continued increases but no normalization Year 2 Therapeutic Goals: Thrombocytopenia* *Please note regular assessments will be conducted.

10 Therapeutic Goals: Pulmonary Involvement* Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14. PatientsGoal Patients with overt, symptomatic pulmonary involvement**  Reverse hepatopulmonary syndrome and dependency on oxygen  Ameliorate pulmonary hypertension  Improve functional status and quality of life  Prevent rapid deterioration of pulmonary disease and sudden death All patients  Prevent pulmonary disease by timely initiation of treatment and avoidance of splenectomy ** Most patients in this group have had spleen removed. *Please note regular assessments will be conducted.

11 Therapeutic Goals: Bone Disease* Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14. PatientsGoalTime Frame All patients  Lessen or eliminate bone pain  Prevent bone crises  Prevent osteonecrosis and subchondral joint collapse 1 to 2 years Pediatric patients  Improve BMD  Attain normal or ideal peak skeletal mass  Increase cortical and trabecular BMD  Improve BMD  Increase trabecular BMD 2 years Adult patients *Please note regular assessments will be conducted. 3–5 years

12 Therapeutic Goals: Pediatric Growth and Functional Health and Well-being* Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14. Pediatric Growth PatientsGoalTime Frame Pediatric patients  Normalize growth such that patient achieves a normal height according to population standards Within 3 years Pediatric patients  Achieve normal onset of puberty Functional Health and Well-being Patients GoalTime Frame All patients  Improve or restore physical function for carrying out normal daily activities and fulfilling functional roles All patients  Improve scores from baseline of a validated quality-of-life instrument 2–3 years or less (depending on disease burden) *Please note regular assessments will be conducted.

13 A Comprehensive Management Plan  Defined specific management goals Act as a guide for managing physicians, consulting specialists, allied health personnel Educate patients and families Establish reasonable expectations  Most patients will have multiple therapeutic goals To be completed within an expected timeframe Maintained for life  Success depends on Comprehensive initial assessment of all potentially affected organs and systems Regular monitoring Pastores GM, et al. Semin Hematol. 2004;41(4 suppl 5):4–14.

14 Recommendations for Monitoring: Achieved vs Not Achieved Therapeutic Goals  Patients on Therapy: For those who are receiving therapy, the frequency of recommended evaluations is dependent on whether or not a particular patient has achieved his or her therapeutic goals Not Achieved Therapeutic Goals: Until the therapeutic goals have been met, it is advisable to have hemoglobin levels, platelet counts, and biochemical markers checked at least every 3 months. A thorough physical examination, as well as visceral and skeletal evaluations, should be completed annually Achieved Therapeutic Goals: Once a clear and sustainable response to treatment has been established, the recommended frequency for checking lab values, visceral response, and skeletal disease diminishes, allowing for routine monitoring every 12–24 months (at a minimum). However, a thorough physical examination should be conducted annually Weinreb NJ, et al. Semin Hematol. 2004;41(suppl 5):15–22.

15 The Therapeutic Goals MAP Tool   Designed as a point-of-care management tool by an international taskforce Provides a visual representation of patient status and therapeutic outcomes over time  The MAP tool can be adapted for different patient populations For pediatric patients, growth will be displayed as an additional domain For splenectomized patients, the splenomegaly domain is omitted  A biomarker domain can also be incorporated for chitotriosidase (CHITO) and chemokine (C-C motif) ligand 18 (CCL18)  Hard copy and electronic versions have been developed

16 Therapeutic Goals MAP Tool  (electronic) – Adult and Pediatric Version © Shire Pharmaceuticals Group, AdultPediatric

17 Therapeutic Goals MAP

18 Expanding Adoption of Therapeutic Goals May Assist With Benefit Patient Care Encourage and facilitate use of therapeutic goals in day-to-day clinical practice Novel, user-friendly, visual point-of-care assessment Many patients do not currently achieve all the guideline therapeutic goals 1 Standardize a goal-oriented approach, in tandem with regular monitoring, to optimize patient care 1. Weinreb NJ, et al. Am J Hematol. 2008;83:890–895. Help in the building of partnerships between physicians and patients

19 Therapeutic Goals MAP Tool – Summary  Allows physicians to collate clinical data over time and help guide management by tracking patient progress using therapeutic goal domains  Allows other specialists and allied healthcare professionals to closely follow patients’ progress  Importantly, by further engaging patients and families in the management process and enhancing their understanding of clinical outcomes, use of the MAP tool may create create a partnership in caring  For more information, please visit or also contact a Shire Global Medical Affairs representativewww.therapeuticgoalsmap.com


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