Characteristics of a Swedish Patient Registry and Its Application On Unmet Needs AnalysisDr. Dan Mellström1, Arun Krishna2, Zhyi Li3, Chun-Po Steve Fan3, Stina Salomonsson2, Dr. Ewa Waern1

1Centre for Bone and Arthritis Research at Sahlgrenska Academy, University of Gothenburg, Sweden; 2Merck & Co., Inc.; 3AsclepiusJT LLC

Characteristics of a Swedish Patient Registry and Its Application On Unmet Needs AnalysisDr. Dan Mellström1, Arun Krishna2, Zhyi Li3, Chun-Po Steve Fan3, Stina Salomonsson2, Dr. Ewa Waern1

1Centre for Bone and Arthritis Research at Sahlgrenska Academy, University of Gothenburg, Sweden; 2Merck & Co., Inc.; 3AsclepiusJT 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.

BackgroundEstablishment 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 40o 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 diseaseso 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 RegistryContains critical variables of interest

• Fracture info • BMD (T-score) • OP treatment

• OP diagnosis • EQ-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 test2) Diagnosed for OP3) Completed questionnaire

Low BMD and/or

OP diagnosis

1) Received BMD test2) Diagnosed for OP3) Completed questionnaire

Continued follow-up every 2 years ifLow BMD and/or

OP diagnosis

Normal BMDor

no OP diagnosis

Patient exit registry

Year 2

Normal BMDOr

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 RegistryHigh 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)

Characteristics Type Patient Count Percentage

Patient At enrollment 9,312 100.0%2 visits 4,080 43.8%> 2 visits 1,821 19.6%

BMDAt enrollment 9,228 99.1%2 measurements 2,234 24.0%> 2 measurements 1,780 19.1%

EQ-5D*With measurement** 3,240 34.8%At enrollment 1,570 16.9%No measurement 6,072 65.2%

OP treatment at enrollment

Currently treated 1,804 19.4%Previously treated 845 9.1%Both 875 9.4%Neither 5,788 62.2%

Diagnosis at enrollment

Normal BMD 1,688 18.1%Osteopenia 4,031 43.3%Osteoporosis 3,587 38.5%Other*** 6 0.1%

Fracture (after age 40) at enrollment

No 7,173 77.0%Yes 2,139 23.0%

* 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 patientso Analysis of under-treatment and reasons for

non-adherence

Application of Swedish Registry:   N % N respondedPatient characteristics      Female 8,481 91% 9,312Age (mean, std) 64.1 11.8 9,312Weight [kg] (mean, std) 66.1 20.6 8,970Height [cm] (mean, std) 161.4 22.3 8,965Current smoker 3,042 33% 9,312Fractures after age>40 2,141 23% 9,312Family history of fractures 1,290 14% 9,312Suffered daily back pain 2,632 28% 9,312

T-score      Total hip     9,150-2.5< T-score < -1 4,200 46%  T-score≤ -2.5 1,661 18%  

Lumbar spine     9,196-2.5< T-score < -1 3,460 38%  T-score≤ -2.5 2,724 30%  

Total hip or lumbar spine     9,228-2.5< T-score < -1 3,897 42%  T-score≤ -2.5 3,292 36%  

Table 3. EQ-5D (N=1,570)

 EQ-5D mean stdMobility 1.37 0.49

Answered: I have no problems (N, %) 1,065Self-care 1.11 0.35

Answered: I have no problems (N, %) 1,521Activities 1.34 0.56

Answered: I have no problems (N, %) 1,189Pain/Discomfort 1.91 0.60

Answered: I have no pain (N, %) 381Anxiety/Depression 1.52 0.57

Answered: I have not anxious or depressed (N, %) 866

ObjectiveTo 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)

2nd 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   392 297 90Worsen BMD 90 23.0% 81 27.3% 90 100.0%Remainedosteoporotic 297 75.8% 297 100.0% 81 90.0%

T-score baseline        Hip -2.30 0.93 -2.42 0.92 -2.15 0.92  Spine -3.00 0.98 -3.14 1.01 -2.81 1.26 T-score post baseline        Hip -2.04 0.97 -2.20 0.97 -2.24 0.96  Spine -2.57 1.05 -2.82 1.01 -2.80 1.09 T-score change        Hip 0.26 0.53 0.22 0.55 -0.09 0.61  Spine 0.43 0.65 0.32 0.61 0.02 0.94Length between visits (year) 2.71 0.98 2.70 1.00 2.76 1.04

    All (trmt ≥ 2 years)

Remained osteoporotic Worsen BMD

    N % N % N %

N   392 297 90Fracture      

  Between baseline and 2nd visit 23 5.9% 10 3.4% 4 4.4%

Patients with 3 or more visits 48 36 12

  Fractures after the 2nd visit 5 10.4% 4 11.1% 2 16.7%

Treatment received        BIS 301 76.8% 215 72.4% 43 47.8%  Fosamax 75 19.1% 54 18.2% 9 10.0%  Fosamax 70 107 27.3% 69 23.2% 7 7.8%  Optinate 43 11.0% 33 11.1% 9 10.0%  Optinate septimum 37 9.4% 27 9.1% 7 7.8%  Didronate 52 13.3% 43 14.5% 14 15.6%  Non_BIS/Evista 95 24.2% 86 29.0% 48 53.3%

Study DesignThis 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

ConclusionUsing 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 questions1 = No Problem , 2 = Some Problem, 3 = Extreme Problem or Not Able to Perform