1. Characteristics of a Swedish Patient Registry and Its Application On Unmet Needs Analysis Dr. Dan Mellström 1, Arun Krishna 2, Zhyi Li 3, Chun-Po Steve Fan 3, Stina Salomonsson 2, Dr. Ewa Waern 1 1 Centre for Bone and Arthritis Research at Sahlgrenska Academy, University of Gothenburg, Sweden; 2 Merck & Co., Inc.; 3 AsclepiusJT LLC Characteristics of a Swedish Patient Registry and Its Application On Unmet Needs Analysis Dr. Dan Mellström 1, Arun Krishna 2, Zhyi Li 3, Chun-Po Steve Fan 3, Stina Salomonsson 2, Dr. Ewa Waern 1 1 Centre for Bone and Arthritis Research at Sahlgrenska Academy, University of Gothenburg, Sweden; 2 Merck & Co., Inc.; 3 AsclepiusJT LLC Objective To provide an overview of a Swedish osteoporosis patient registry - describe characteristics, treatment patterns and quality of life among subjects enrolled in the registry. To utilize this registry for analyzing unmet needs of osteoporosis – those remaining at a high risk of fractures despite benefit from prior treatment. Background Establishment of registry The registry was established at the osteoporosis clinic at Sahlgrenska University hospital, Göteborg, in the West region of Sweden encompassing about 2 million inhabitants. Patients were referred to enter the registry by GPs, gynecologists, etc for dual- energy X-ray absorptiometry (DXA) for bone mineral density (BMD) assessment and diagnosis of osteoporosis (OP) A follow-up visit would be scheduled in every other year if low BMD and/or OP diagnosis was indicated in the prior visit. If the follow-up visit was cancelled, then the patient would no longer be followed. Data availability:1991 to 2009. Information collected at each visit Clinical assessments: o Patient’s info (age, gender, height, and weight) o BMD scan results (lumbar/spine, total hip and total body) o T-score (lumbar/spine, total hip and total body), o Diagnosis (Normal, Osteopenia, established OP, OP, Male OP) o Type of referrals (GPs, gynecologists, orthopedists, rheumatologists, or other) o Comorbid conditions (secondary OP, rheumatoid arthritis etc) Self-reported outcomes (through self-completing questionnaire): o Fractures after age 40 o Patient characteristics (smoking status, alcohol, back pain, family history of fractures, history of falls) o Current and previous use of OP treatment and glucocorticoids o History of chronic diseases o Quality of life using EQ-5D (collected after 2004) Presented at The American Society for Bone and Mineral Research (ASBMR) 2013 Annual Meeting, Baltimore, MD, October 4 – 7, 2013 Plenary Poster FR 0404 / Poster session 1 SA 0404 Advantage of the Swedish Registry Contains critical variables of interest Fracture infoBMD (T-score)OP treatment OP diagnosisEQ-5D Longitudinal data over time ~4,000 (45%) patients with 2 or more visits Collection Period:1999 - 2009 Patient entered registry 2004 Started collecting EQ-5D in questionnaire Year 0 1) Received BMD test 2) Diagnosed for OP 3) Completed questionnaire Low BMD and/or OP diagnosis 1) Received BMD test 2) Diagnosed for OP 3) Completed questionnaire Continued follow- up every 2 years if Low BMD and/or OP diagnosis Normal BMD or no OP diagnosis Patient exit registry Year 2 Normal BMD Or No OP diagnosis Patient exit registry Follow-up visit Subjects were invited for a follow-up visit every 2 years if the prior visit showed low BMD/OP diagnosis Summary of the Registry High level summary 9,312 subjects were enrolled in the registry, 38.5% (3,587) were diagnosed with OP and 43.3% (4,031) with osteopenia at enrollment (Table 1) CharacteristicsTypePatient CountPercentage Patient At enrollment9,312100.0% 2 visits4,08043.8% > 2 visits1,82119.6% BMD At enrollment9,22899.1% 2 measurements2,23424.0% > 2 measurements1,78019.1% EQ-5D* With measurement**3,24034.8% At enrollment1,57016.9% No measurement6,07265.2% OP treatment at enrollment Currently treated1,80419.4% Previously treated8459.1% Both8759.4% Neither5,78862.2% Diagnosis at enrollment Normal BMD1,68818.1% Osteopenia4,03143.3% Osteoporosis3,58738.5% Other***60.1% Fracture (after age 40) at enrollment No7,17377.0% Yes2,13923.0% * Only those with complete response to all EQ-5D questions ** EQ-5D started on 2004, therefore the first measurement was not necessary recorded at enrollment *** Including “Fibrous dysplasia”, “Skeletal fluorosis”, “other bone disorder” Table 1. High level summary counts of the registry Patient characteristics at enrollment 91% were female, with average age of 64.1 [SD=11.8] years. Average weight and height were 66.1 [SD=20.6] kg and 161.4 [SD=22.3] cm, respectively. (Table 2) 23% of patients reported prior history of fracture after age 40, 35% had family history of fractures, 28% had back pain, and 33% were currently smokers. (Table 2) From the first DXA scan at enrollment, 36% (3,292) patients had a T-score (either hip or lumbar spine) ≤ -2.5 and 42% (3,897) between -1 and -2.5. (Table 2) Among 2,101 diagnosed with OP at enrollment and having ≥1 follow-up visit, 55% (1,146) received bisphosphonates (BIS) (alendronate, optinate, and etidronate), 12% (259) received non-BIS (raloxifene and teriparatide), 79% (1,651) received calcium+vitamin D, and 26% (542) received estrogen. EQ-5D was available for 1,570 patients whose first visit was post-2004. The average scores were as follow: mobility: 1.37 [SD=0.49], self-care: 1.11 [SD=0.35], usual activities: 1.34 [SD=0.56], pain/discomfort: 1.91 [SD=0.60], and anxiety/depression: 1.52 [SD=0.57]. (Table 3) Table 2. Patient characteristics at enrollment Conclusion The Swedish patient registry presents opportunities to understand various unmet needs among OP patients as a result of extensive information collected overtime. Examples of analyses include: o Estimation of patients remained at “high risk” of fracture despite benefit of prior treatment o Analysis of Quality of life of OP patients o Analysis of under-treatment and reasons for non-adherence Application of Swedish Registry: N%N responded Patient characteristics Female8,48191%9,312 Age (mean, std)64.111.89,312 Weight [kg] (mean, std)66.120.68,970 Height [cm] (mean, std)161.422.38,965 Current smoker3,04233%9,312 Fractures after age>402,14123%9,312 Family history of fractures1,29014%9,312 Suffered daily back pain2,63228%9,312 T-score Total hip 9,150 -2.5< T-score < -14,20046% T-score≤ -2.51,66118% Lumbar spine 9,196 -2.5< T-score < -13,46038% T-score≤ -2.52,72430% Total hip or lumbar spine 9,228 -2.5< T-score < -13,89742% T-score≤ -2.53,29236% Table 3. EQ-5D (N=1,570) EQ-5Dmeanstd Mobility1.370.49 Answered: I have no problems (N, %)1,065 Self-care1.110.35 Answered: I have no problems (N, %)1,521 Activities1.340.56 Answered: I have no problems (N, %)1,189 Pain/Discomfort1.910.60 Answered: I have no pain (N, %)381 Anxiety/Depression1.520.57 Answered: I have not anxious or depressed (N, %)866 Objective To examine the proportion/characteristics of osteoporotic patients remaining at a high risk despite being treated for ≥ 2 years. “High risk” was defined as: Patients with deteriorating/worsen BMD, defined as T-score decrease ≥ 3% at either hip or spine Patients remaining osteoporotic, defined as T-score ≤ -2.5 at either hip or spine Patients experienced fracture after baseline visit Baseline (Visit 1) 2 nd visit (Visit 2) Step 1: (Patient Selection) Osteoporotic (BMD ≤-2.5), and Treatment naïve Treatment ≥ 2 years Step 3: (Outcome measures) % with deteriorating/worsen BMD % remaining osteoporotic % with fracture Step 2: (Determine treatment duration) Patient reported how long they have been treated since last visit Study diagram Results All (trmt ≥ 2 years) Remained osteoporotic Worsen BMD N%N%N% N 39229790 Worsen BMD9023.0%8127.3%90100.0% Remained osteoporotic 29775.8%297100.0%8190.0% T-score baseline Hip-2.300.93-2.420.92-2.150.92 Spine-3.000.98-3.141.01-2.811.26 T-score post baseline Hip-2.040.97-2.200.97-2.240.96 Spine-2.571.05-2.821.01-2.801.09 T-score change Hip0.260.530.220.55-0.090.61 Spine0.430.650.320.610.020.94 Length between visits (year) 2.710.982.701.002.761.04 All (trmt ≥ 2 years) Remained osteoporotic Worsen BMD N%N%N% N 39229790 Fracture Between baseline and 2nd visit 235.9%103.4%44.4% Patients with 3 or more visits 483612 Fractures after the 2nd visit 510.4%411.1%216.7% Treatment received BIS30176.8%21572.4%4347.8% Fosamax7519.1%5418.2%910.0% Fosamax 7010727.3%6923.2%77.8% Optinate4311.0%3311.1%910.0% Optinate septimum379.4%279.1%77.8% Didronate5213.3%4314.5%1415.6% Non_BIS/Evista9524.2%8629.0%4853.3% Study Design This is a descriptive study using Swedish patient registry data, the inclusion criteria were: Osteoporotic at baseline (BMD≤ -2.5, either hip or spine) Treatment naïve at baseline Returned for a 2nd visit for BMD measurements Proportion and Characteristics of Patients Remaining at “High Risk” Despite Benefit from Prior Treatment Conclusion Using the Swedish Registry data, we found a large proportion of patients remained osteoporotic, and were at a high risk of developing fractures despite being treated for ≥ 2 years. 75.8% (297/392) patients remained osteoporotic, 23.0% (90/392) patients had worsen BMD, 5.9% (23/392) patients experienced fracture prior to their second visit. Table 4. Proportion of patients remaining osteoporotic and with worsen BMD Table 5. Fracture and treatment received Responses to each of the 5 EQ-5D questions 1 = No Problem, 2 = Some Problem, 3 = Extreme Problem or Not Able to Perform