Contributions to health outcomes research Rheumatoid Arthritis. Study objective: Database: Author: Version: Date:

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1 Contributions to health outcomes research Rheumatoid Arthritis Study objective: Database: Author: Version: Date: Analysis of patient journeys and their resource consumptions in Germany Insurants presenting rheumatoid arthritis in Germany Statutory Health Insurance (SHI) - an exploratory retrospective analysis based on German claims data. HRI research database (FDB), 4m patients, longitudinal (6 years) Elsevier Health Analytics Pre-release, no commercial use Elsevier GmbH, Elsevier Health Analytics, all rights reserved, April 2016

2 ToC Sheet 0C Abbr. 0D Data 0E Validity 0F Selection I Incidence I Sector I Persistence I Disciplines I Comorb. I Therapy I Therapy Change I I Therapy change II I Cost P Prevalence P Persistence P Burden P Act. treat P Act. treat. AGG P Therapy P Biologics P Biol. change P Biol. dur. P Biol. dur. II P Biol. pre-exist. P Biol. dis. P Cost P Cost regime P Hosp. P Sick leave Content Abbreviations Overview of data samples used (HRI research database) External data validity Study population selection Number of new diseases Sector of initial diagnosis Repeated documentation after initial diagnosis Disciplines diagnosing the investigated disease Top 20 comorbidities (ICD-3-level) prior to initial diagnosis Drugs prescribed after initial diagnosis Course of therapy - aggregated view Course of therapy Average cost in the different health service areas in prevalent patients Occurence of the investigated diagnosis in the study population Occurence of the investigated diagnosis Burden of disease Active treatment in the year after selection Patients with active treatment grouped by age and sex Prescribed substance classes in the year after selection Prescriptions of Biologics Change of therapy among biologics Average period until therapy change or termination of biologics therapy Average period until therapy change or termination of biologics treatment part II Period with pre-existing diagnosis prior to biologicals therapy Disciplines initiating a biologicals therapy Total cost over 3 years Cost by highhest therapy regime Hospitalizations in patients presenting RA Inability to work in patients presenting RA Page 1

3 Abbreviations Abbreviation Term % percent Sum abs. absolute amb. ambulant diag. diagnose max. maximum min. minimum N number of insurants (disjunct) or number of observed entities Ø average o.g. aforementioned RA rheumatoid arthritis Std. standard deviation NSAID Non-steroidal anti-inflammatory drug DMARD Disease modifiing antirheumatic drug Page 2

4 Overview of the HRI-research database (FDB) and included samples! anonymized claims data of approx. 6 mio. insurants including a 6 year history! representative sample for Germany including long-time longitudinal analysis stratified according to the official demografic structure (DeStatis, ) 2 stratified samples:! FDB-ANALYSE! FDB-DESTATIS Size:! ca. 4 Mio. insurants! ca. 1 Mio. insurants Stratified by:! Age + Sex! Age + Sex counties Master File Data Primary Care Sector Pharmacy Hospital Inability to Work Supporting Measures Age Sex Insurance days DMP Date of death ICD-10 OPS EBM Discipline ATC PZN Discipline Prescription Date Hand out date # Packages ICD-10 DRG OPS Lenght of stay Admission diagnosis Discharge diagnosis ICD-10 Sick leave days Sick leave days with pay Sick leave cost Product Amount Indication Measure Regional Data: County and KV-Region Cost Data for all sectors " Analysis alongside the patient treatment path possible The Health Risk Institute (HRI) was founded in 2011 to pool sickness funds claims data of 75 German statutory health insurers so as to develop patient-level risk predictions and to conduct outcomes research. The data is provided in accordance with paragraphs 287 SGB V and 75 SGB X of German law. Data on patients and physicians is anonymized, as are the providers and the sickness funds, before data is made available to the Health Risk Institute. No regions smaller than federal states or cohorts with less than 100 patients are identified. The HRI functions as the safe haven for data processing, statistics, predictive analytics, and outcomes research, ensuring the highest levels of patient data security. The HRI database is a complete, longitudinal claims data set of 7 million individual patients (ca. 10% of the statutory insured population ) between 2008 and This size of this dataset has been reduced to a 4.0 million patient sample representative of the German population in terms of age and gender (as of ). The HRI database includes information about the utilization of services on a case-by-case individual level. To support claims, indications (ICD10-GM) and procedure codes are provided together with costs. As German statutory insurance patients have coverage for all health care services, only few co-payments exist (typically the cost of OTC medication). The amount paid out by sickness funds to providers (e.g. hospitals, physicians, pharmacies, psychotherapists, physiotherapists) therefore is a close-to-complete picture of an individual s total health care costs. The claims database does not include any direct clinical parameters (e.g. lab test results, results of bone density tests, quality of life data, severity grades of a disease, symptom scores etc.). Sickness funds in Germany may receive this data only with express patient consent and not as a matter of routine. Page 3

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6 Selection of the study population Population N % Extrapolation Germany Insurants Observable without interruption between 2010 and 2014 or deceased after ,00% Selection criteria* present ,54% and without selection diagnosis in ,30% * Selection criteria: Diagnosis of rheumatoide arthritis (ICD M05 or M06 as hospital diagnosis or verified ambulant diagnosis) and age > 18 years This indication report is generated based on a non-interventional retrospective claims database study from the HRI database. For an insured person to be included in the study, he/she must be observable without interruption between 1 Jan, 2009 and 31 Dec, 2014 or have died after 31 Dec, The quarter of the first RA diagnosis (see inclusion criteria below) is defined as index date (index quarter). For analyses of patient journeys over time, patient-individual intervals of -12 (prior period) and +8 (follow-up) quarters are defined around the index quarter. The index quarter is considered separately in all analyses that focus on development over time. For analysis of treatment-related research questions, the first day of therapy is defined as treatment initiation date. In the research database information for prescriptions is available with precision of days as compared to diagnoses which are only known by the quarter. Thus, time between first diagnosis and treatment initiation is also only known on the level of the quarter whereas medical treatment over time can measured with daily precision. In all analysis the minimum number of reported patient counts must be more than 4. In case of less than 5 found individuals the found number is reported as < 5 and the exact number found is not included in the totals of all individuals. Page 5

7 Population 2012 Germany, Source: DeStatis Age group Male Female Total > Total FDB Analyse Observable Rheumatoide Arthritis New diseases No drug therapie Drug therapy Biologics No Biologics Page 6

8 Rheumatoid Arthritis: Incidence Table 1: New RA-diagnoses in 2012 by age and sex and extrapolation for Germany Incidence Sex Age N / N Germany > Female Total > Male Total > All Total New dieeases / Rheumatoid Arthritis: Incidence rate by age and sex > 79 Age Female Male All Figure 1a: Rheumatoide Arthritis - New diseases per Rheumatoid Arthritis: New diseases in Germany > 79 Female Male All Figure 1b: Rheumatoid Arthritis - New diseases in Germany 2012 Page 7

9 Rheumatoid Arthritis: Sector of first diagnosis Table 2: Abs. and rel. frequencies of incident insurants by sector of first diagnosis and sex Female Male Total Sector N % N % N % ambulatory care (office-based) ,30% ,45% ,02% hospital outpatient care 105 1,52% 34 0,99% 139 1,34% hospital inpatient care 92 1,33% 78 2,26% 170 1,64% diagnosis in both sectors 127 1,84% 79 2,29% 206 1,99% Total % % % 100% 90% 80% Sector of initial rheumatoid arthritis diagnosis 70% 60% 50% 40% 30% diagnosis in both sectors hospital inpatient care hospital outpatient care ambulatory care (office-based) 20% 10% 0% Figure 2: Sector of first Rheumatoid Arthritis diagnosis Page 8

10 Rheumatoid Arthritis: Persistence of the diagnosis subsequent to the initial diagnosis Table 3: Abs. and rel. frequencies of quarters with RA-diagnosis subsequent to the initial diagnosis by age group >= 80 Total Quarter N % N % N % N % N % N % N % N % % 80 24% % % % % % % % 52 16% % % % % 93 14% % % 35 11% 55 7% 128 9% 109 9% 101 7% 55 8% 515 9% % 23 7% 52 7% 84 6% 88 7% 101 7% 27 4% 395 7% 5 7 4% 15 5% 40 5% 75 5% 69 6% 57 4% 28 4% 291 5% % 13 4% 32 4% 62 4% 46 4% 52 4% 27 4% 242 4% 7 9 5% 13 4% 31 4% 41 3% 44 4% 45 3% 25 4% 208 3% % 99 30% % % % % % % Total % % % % % % % % Proportion of patients 45% 40% 35% 30% 25% 20% 15% 10% 5% Persistence of the RA-diagnosis in incident patients 0% Quarter Figure 3: Incident rheumatoid arthritis - Persistence of the diagnosis Page 9

11 Rheumatoid Arthritis: Disciplines documenting the initial diagnosis Table 4: Abs. and rel. frequencies of diciplines documentig the initial RA diagnosis by sex Female Male Total Discipline N % N % N % Other ,99% ,99% ,66% Family Medicine ,54% ,34% ,81% Internal / Rheumathology ,69% ,38% ,92% Orthopedics 689 9,99% 300 8,71% 989 9,56% Internal Medicine 532 7,71% 200 5,81% 732 7,08% Ophthalmology 202 2,93% 112 3,25% 314 3,04% Surgery / Rheumatology 217 3,15% 87 2,53% 304 2,94% Total % % % Rheumatoid Arthritis: Discipline documenting the initial diagnosis 3,04% 2,94% 9,56% 15,92% 7,08% 15,66% 45,81% Other Family Medicine Internal / Rheumathology Orthopedics Internal Medicine Ophthalmology Surgery / Rheumatology Figure 4: Rheumatoid Arthritis - Disciplines making the initial diagnosis Page 10

12 Rheumatoid Arthritis: The 20 most often observed comorbidities in the 8 quarters before the initial diagnosis Table 5: Abs. and rel. frequencies of the 20 most frequent comorbidities in incident patients in the 8 quarters before initial diagnosis compared to a risk adjusted control group Rheumatoide Control group deviation ICD 10 Comorbidity N % N % % M54 Dorsalgia ,4% ,1% 12,5% I10 Essential (primary) hypertension ,2% ,3% -2,6% Z12 Encounter for screening for malignant neoplasms ,0% ,2% -11,9% H52 Disorders of refraction and accommodation ,7% ,8% -7,6% E78 Disorders of lipoprotein metabolism and other lipidemias ,6% ,7% -9,8% Z00 Encntr for general exam w/o complaint, susp or reprtd dx ,2% ,5% -20,0% M25 Other joint disorder, not elsewhere classified ,1% ,6% 81,0% M79 Oth and unsp soft tissue disorders, not elsewhere classified ,1% ,5% 103,3% M47 Spondylosis ,1% ,9% 21,5% Z25 Need for immunization against other single viral diseases ,0% ,1% -11,9% M53 Other and unspecified dorsopathies, not elsewhere classified ,0% ,8% 20,3% M17 Osteoarthritis of knee ,0% ,7% 31,5% F32 Major depressive disorder, single episode ,0% ,9% 10,8% N95 Menopausal and other perimenopausal disorders ,0% ,0% -6,7% F45 Somatoform disorders ,9% ,8% 20,5% M99 Biomechanical lesions, not elsewhere classified ,9% ,7% 17,4% M19 Other and unspecified osteoarthritis ,8% ,5% 68,8% N89 Other noninflammatory disorders of vagina ,8% ,0% -14,1% R10 Abdominal and pelvic pain ,8% ,9% -8,7% M51 Thoracic, thoracolum, and lumbosacral intvrt disc disorders ,8% ,6% 26,9% Page 11

13 Rheumatoid Arthritis: Drugs prescribed during the 8 quarters subsequent to initial diagnosis Table 6: Abs. and rel. frequensies of prescribed drugs in incident insurants in the 8 quarters subsequent to the initial RA-diagnosis Q1 Q2 Q3 Q4 Q1 bis Q4 Substance group N % N % N % N % N % Biologics 32 0,3% 66 0,6% 105 1,0% 168 1,6% 183 1,8% Corticoids 635 6,1% ,6% ,1% ,9% ,0% DMARDs 466 4,5% 894 8,6% ,9% ,3% ,0% NSAIDs 702 6,8% ,2% ,5% ,0% ,8% Min. one of the above ,9% ,6% ,2% ,2% ,1% Q5 Q6 Q7 Q8 Q5 bis Q8 Q1 bis Q8 Substance group N % N % N % N % N % N % Biologics 173 1,7% 186 1,8% 186 1,8% 206 2,0% 270 2,6% 285 2,8% Corticoids ,9% ,2% ,6% ,2% ,2% ,4% DMARDs ,7% ,7% ,5% ,3% ,9% ,2% NSAIDs ,4% ,1% ,7% ,3% ,9% ,9% Min. one of the above ,3% ,9% ,3% ,9% ,9% ,4% 30% Rheumatoide Arthritis: Drugs prescribed subsequent to initial diagnosis 25% 20% 15% 10% 5% 0% Figure 6: Rheumatoid Arthritis: Drugs prescribed subsequent to initial diagnosis Included pharmacologic substances Biologics Corticoids DMARDs NSAIDs Substance group Biologics Corticoids DMARDs NSAIDs L04AB TNF Inhibitors L04AC Interleukin Inhibitors L04AA24 Abatacept L01XC02 Rituximab H02A - Systemic Corticosteroids H02B - Systemic Corticosteroids, Combinations L01AA01 - Cyclophosphamide L04AD - Calcineurin Inhibitors L04AX - Other Immunosuppressors M01C - Specific Antirheumatics P01BA01 - Chloroquine P01BA02 - Hydroxychloroquine N02BB02 - Metamizole Sodium M01A - Non-steroidal anti-inflammatory drugs ATC Page 12

14 Rheumatoide Arthritis: Change in therapy in the 8 quarters subsequent to the initial diagnosis Table 7: Abs. and rel. frequencies of therapy changes in patients presenting a new diagnosis of rheumatoid arthritis Q1 to Q2 Q2 to Q3 Q3 to Q4 Q4 to Q5 Q5 to Q6 Q6 to Q7 Q7 to Q8 Change N % N % N % N % N % N % N % 00-> ,21% ,88% ,59% ,01% ,65% ,39% ,73% 00-> ,17% 685 6,62% 890 8,61% 660 6,38% 595 5,75% 636 6,15% 639 6,18% 00-> ,08% 571 5,52% 623 6,02% 294 2,84% 260 2,51% 285 2,76% 271 2,62% 00-> ,31% 626 6,05% 741 7,17% 359 3,47% 369 3,57% 388 3,75% 409 3,95% 00-> ,32% 35 0,34% 45 0,44% 13 0,13% 19 0,18% 10 0,10% 20 0,19% 01-> ,02% 324 3,13% 524 5,07% 672 6,50% 693 6,70% 634 6,13% 612 5,92% 01-> ,49% 303 2,93% 396 3,83% 587 5,68% 585 5,66% 533 5,15% 541 5,23% 01-> ,19% 54 0,52% 68 0,66% 94 0,91% 90 0,87% 89 0,86% 79 0,76% 01-> ,43% 87 0,84% 122 1,18% 143 1,38% 148 1,43% 147 1,42% 158 1,53% 01->04 <5 0,00% 6 0,06% 6 0,06% <5 0,00% <5 0,00% 6 0,06% 5 0,05% 02-> ,92% 175 1,69% 307 2,97% 318 3,07% 358 3,46% 298 2,88% 312 3,02% 02-> ,39% 58 0,56% 101 0,98% 127 1,23% 107 1,03% 88 0,85% 84 0,81% 02-> ,02% 371 3,59% 506 4,89% 700 6,77% 602 5,82% 578 5,59% 567 5,48% 02-> ,67% 109 1,05% 182 1,76% 191 1,85% 210 2,03% 181 1,75% 153 1,48% 02->04 <5 0,00% 6 0,06% 10 0,10% 8 0,08% 19 0,18% 15 0,15% 18 0,17% 03-> ,24% 211 2,04% 328 3,17% 511 4,94% 437 4,23% 419 4,05% 449 4,34% 03-> ,41% 68 0,66% 111 1,07% 141 1,36% 117 1,13% 134 1,30% 122 1,18% 03-> ,65% 109 1,05% 146 1,41% 202 1,95% 195 1,89% 178 1,72% 159 1,54% 03-> ,11% 488 4,72% 716 6,92% 898 8,68% 842 8,14% 835 8,07% 821 7,94% 03->04 <5 0,00% <5 0,00% 10 0,10% 11 0,11% 6 0,06% 8 0,08% 8 0,08% 04->00 <5 0,00% 8 0,08% <5 0,00% 15 0,15% 11 0,11% 23 0,22% 13 0,13% 04->01 <5 0,00% <5 0,00% <5 0,00% <5 0,00% 5 0,05% <5 0,00% 5 0,05% 04->02 <5 0,00% <5 0,00% <5 0,00% 6 0,06% 13 0,13% <5 0,00% 6 0,06% 04->03 0 0,00% <5 0,00% <5 0,00% 6 0,06% 5 0,05% 8 0,08% 7 0,07% 04-> ,24% 54 0,52% 97 0,94% 137 1,32% 139 1,34% 147 1,42% 155 1,50% Total % % % % % % % Legend: Code Regime no specific RA therapy NSAIDs and no 02, 03, 04 Corticoids and no 03, 04 DMARDs and no 04 Biologics Page 13

15 Rheumatoide Arthritis: Change in therapy in the 8 quarters subsequent to the initial diagnosis Table 7: Abs. and rel. frequencies of therapy changes in patients presenting a new diagnosis of rheumatoid arthritis Q1 to Q2 Q2 to Q3 Q3 to Q4 Q4 to Q5 Q5 to Q6 Q6 to Q7 Q7 to Q8 Change N % N % N % N % N % N % N % 00-> ,00% ,77% ,78% 983 9,50% ,41% ,02% ,99% 00-> ,16% 489 4,73% 550 5,32% 152 1,47% 172 1,66% 187 1,81% 153 1,48% 00-> ,74% 322 3,11% 313 3,03% 39 0,38% 34 0,33% 29 0,28% 45 0,44% 00-> ,97% 141 1,36% 131 1,27% 15 0,15% 13 0,13% 21 0,20% 8 0,08% 00-> ,73% 179 1,73% 207 2,00% 38 0,37% 39 0,38% 44 0,43% 50 0,48% 00-> ,86% 103 1,00% 101 0,98% 10 0,10% 21 0,20% 24 0,23% 32 0,31% 00-> ,28% 138 1,33% 130 1,26% 12 0,12% 14 0,14% 10 0,10% 10 0,10% 00-> ,65% 60 0,58% 63 0,61% 5 0,05% 5 0,05% <5 0,00% <5 0,00% 00-> ,10% 14 0,14% 23 0,22% <5 0,00% 5 0,05% <5 0,00% 5 0,05% 00->09 <5 0,00% 5 0,05% <5 0,00% <5 0,00% 0 0,00% <5 0,00% <5 0,00% 00->0X ,76% ,74% ,39% 415 4,01% 425 4,11% 495 4,79% 501 4,84% 00->10 <5 0,00% <5 0,00% 7 0,07% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 00->11 5 0,05% <5 0,00% <5 0,00% <5 0,00% 0 0,00% <5 0,00% <5 0,00% 00->12 <5 0,00% <5 0,00% <5 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 00->13 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 00->14 <5 0,00% <5 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 00->15 <5 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 01-> ,78% 93 0,90% 125 1,21% 178 1,72% 195 1,89% 170 1,64% 165 1,60% 01-> ,49% 303 2,93% 396 3,83% 587 5,68% 585 5,66% 533 5,15% 541 5,23% 01->02 5 0,05% 21 0,20% 32 0,31% 38 0,37% 40 0,39% 39 0,38% 37 0,36% 01-> ,15% 33 0,32% 36 0,35% 56 0,54% 50 0,48% 50 0,48% 42 0,41% 01-> ,16% 34 0,33% 37 0,36% 46 0,44% 36 0,35% 59 0,57% 53 0,51% 01-> ,20% 38 0,37% 60 0,58% 64 0,62% 83 0,80% 68 0,66% 77 0,74% 01->06 <5 0,00% 6 0,06% 11 0,11% 11 0,11% 13 0,13% 8 0,08% 8 0,08% 01->07 <5 0,00% 9 0,09% 14 0,14% 22 0,21% 16 0,15% 12 0,12% 20 0,19% 01->08 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 01->09 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 01->0X 128 1,24% 231 2,23% 399 3,86% 494 4,78% 498 4,82% 464 4,49% 447 4,32% 01->10 <5 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% 0 0,00% 0 0,00% 01->11 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 01->12 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 01->13 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 01->14 <5 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 01->15 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 02-> ,19% 37 0,36% 36 0,35% 52 0,50% 53 0,51% 36 0,35% 36 0,35% 02-> ,19% 28 0,27% 41 0,40% 55 0,53% 41 0,40% 42 0,41% 43 0,42% 02-> ,31% 234 2,26% 317 3,07% 453 4,38% 405 3,92% 380 3,67% 366 3,54% 02-> ,15% 45 0,44% 47 0,45% 75 0,73% 59 0,57% 64 0,62% 62 0,60% 02-> ,15% 11 0,11% 31 0,30% 36 0,35% 24 0,23% 32 0,31% 28 0,27% 02->05 <5 0,00% 6 0,06% 6 0,06% 13 0,13% 11 0,11% 8 0,08% 7 0,07% 02-> ,26% 49 0,47% 71 0,69% 69 0,67% 83 0,80% 67 0,65% 56 0,54% 02->07 6 0,06% 14 0,14% 21 0,20% 18 0,17% 25 0,24% 17 0,16% 7 0,07% 02->08 0 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 02->09 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% 02->0X 54 0,52% 105 1,02% 207 2,00% 200 1,93% 236 2,28% 197 1,90% 206 1,99% 02->10 <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 5 0,05% 8 0,08% 02->11 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 02->12 0 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 02->13 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 02->14 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 02->15 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% 03->00 9 0,09% 7 0,07% 12 0,12% 20 0,19% 10 0,10% 17 0,16% 16 0,15% 03-> ,19% 30 0,29% 60 0,58% 72 0,70% 66 0,64% 46 0,44% 41 0,40% 03-> ,25% 35 0,34% 62 0,60% 76 0,73% 68 0,66% 58 0,56% 58 0,56% 03-> ,31% 57 0,55% 80 0,77% 96 0,93% 70 0,68% 76 0,73% 81 0,78% 03->04 5 0,05% <5 0,00% 5 0,05% <5 0,00% 8 0,08% 9 0,09% 8 0,08% 03->05 <5 0,00% 7 0,07% 10 0,10% 12 0,12% 18 0,17% 12 0,12% 11 0,11% 03->06 <5 0,00% 7 0,07% 14 0,14% 15 0,15% 15 0,15% 15 0,15% 20 0,19% 03->07 <5 0,00% 12 0,12% 24 0,23% 24 0,23% 26 0,25% 21 0,20% 16 0,15% 03->08 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% 0 0,00% 03->09 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 03->0X 12 0,12% 26 0,25% 52 0,50% 46 0,44% 59 0,57% 48 0,46% 54 0,52% 03->10 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 03->11 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 0 0,00% <5 0,00% 03->12 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 03->13 <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 03->14 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 03->15 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 04-> ,14% 29 0,28% 38 0,37% 78 0,75% 48 0,46% 61 0,59% 53 0,51% 04-> ,14% 23 0,22% 33 0,32% 51 0,49% 35 0,34% 44 0,43% 39 0,38% 04->02 <5 0,00% 16 0,15% 20 0,19% 26 0,25% 28 0,27% 18 0,17% 24 0,23% 04->03 0 0,00% 5 0,05% <5 0,00% 6 0,06% 9 0,09% 10 0,10% 6 0,06% 04-> ,58% 144 1,39% 217 2,10% 248 2,40% 269 2,60% 252 2,44% 253 2,45% 04-> ,10% 26 0,25% 30 0,29% 40 0,39% 52 0,50% 38 0,37% 48 0,46% 04-> ,10% 19 0,18% 41 0,40% 53 0,51% 43 0,42% 54 0,52% 64 0,62% 04->07 <5 0,00% 9 0,09% 7 0,07% 13 0,13% 7 0,07% 13 0,13% 10 0,10% 04->08 <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 04->09 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 04->0X 49 0,47% 83 0,80% 136 1,32% 229 2,21% 194 1,88% 188 1,82% 210 2,03% 04->10 0 0,00% 0 0,00% <5 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 04->11 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 04->12 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 04->13 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 04->14 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 04->15 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 05->00 6 0,06% 12 0,12% 23 0,22% 32 0,31% 24 0,23% 18 0,17% 31 0,30% 05-> ,18% 33 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16 06->01 <5 0,00% <5 0,00% 7 0,07% 11 0,11% 11 0,11% 10 0,10% 5 0,05% 06-> ,39% 46 0,44% 69 0,67% 84 0,81% 76 0,73% 68 0,66% 69 0,67% 06->03 <5 0,00% 10 0,10% 13 0,13% 13 0,13% 15 0,15% 16 0,15% 8 0,08% 06-> ,14% 33 0,32% 56 0,54% 66 0,64% 67 0,65% 58 0,56% 43 0,42% 06->05 9 0,09% 5 0,05% 10 0,10% 18 0,17% 13 0,13% 15 0,15% 11 0,11% 06-> ,46% 90 0,87% 118 1,14% 157 1,52% 132 1,28% 122 1,18% 132 1,28% 06->07 5 0,05% 14 0,14% 23 0,22% 31 0,30% 17 0,16% 21 0,20% 18 0,17% 06->08 0 0,00% 0 0,00% <5 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% 06->09 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 06->0X 22 0,21% 34 0,33% 41 0,40% 54 0,52% 52 0,50% 45 0,44% 52 0,50% 06->10 <5 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 0 0,00% 06->11 0 0,00% 0 0,00% <5 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 06->12 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 06->13 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 06->14 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% <5 0,00% 0 0,00% 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17 11->08 <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 11->09 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 11->0X 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% 11->10 0 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 0 0,00% 11->11 0 0,00% <5 0,00% 7 0,07% 5 0,05% <5 0,00% <5 0,00% <5 0,00% 11->12 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 11->13 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% 11->14 0 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 0 0,00% 11->15 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 0 0,00% 12->00 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 12->01 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 12->02 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 0 0,00% 12->03 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 12->04 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 12->05 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 12->06 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 12->07 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 12->08 <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 7 0,07% 6 0,06% 12->09 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% 12->0X 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 12->10 0 0,00% 0 0,00% <5 0,00% <5 0,00% 0 0,00% <5 0,00% 0 0,00% 12->11 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 12->12 0 0,00% <5 0,00% 0 0,00% <5 0,00% 5 0,05% 5 0,05% <5 0,00% 12->13 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 12->14 0 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% 0 0,00% <5 0,00% 12->15 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 13->00 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 0 0,00% 13->01 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 13->02 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 13->03 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 13->04 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 13->05 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 13->06 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 13->07 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 13->08 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% 13->09 <5 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% 13->0X 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 13->10 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 13->11 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 13->12 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% 13->13 0 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 13->14 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 13->15 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 14->00 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 14->01 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 14->02 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 14->03 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 14->04 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 14->05 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 14->06 0 0,00% 0 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% 14->07 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 14->08 <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 14->09 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 14->0X 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 14->10 <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% <5 0,00% 14->11 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% 14->12 0 0,00% <5 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% 14->13 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 14->14 0 0,00% <5 0,00% <5 0,00% 0 0,00% <5 0,00% <5 0,00% <5 0,00% 14->15 0 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 15->00 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 15->01 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 15->02 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 15->03 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 15->04 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 15->05 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 15->06 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 15->07 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 15->08 <5 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% 15->09 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 15->0X 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 0 0,00% 15->10 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 15->11 0 0,00% <5 0,00% <5 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 15->12 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 15->13 0 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% <5 0,00% 0 0,00% 15->14 <5 0,00% 0 0,00% 0 0,00% <5 0,00% 0 0,00% 0 0,00% 0 0,00% 15->15 0 0,00% <5 0,00% <5 0,00% 0 0,00% 0 0,00% <5 0,00% <5 0,00% Total % % % % % % % Legend: Code Regime 0X Biologics any therapy no therapy NSAIDs Corticoids NSAIDs, Corticoids DMARDs NSAIDs, DMARDs Corticoids, DMARDs NSAIDs, Corticoids, DMARDs NSAIDs, Biologics Corticoids, Biologics NSAIDs, Corticoids, Biologics DMARDs, Biologics NSAIDs, DMARDs, Biologics Corticoids, DMARDs, Biologics NSAIDs, Corticoids, DMARDs, Biologics Page 16

18 Rheumatoid Arthritis: Development of treatment cost in incident patients Table 20: Average cost in the different health service areas in incident patients presenting rheumatiod arthritis versus risk adjusted comparison group and GKV total average Rheumatoid Arthritis Year of selection Year 1 Year 2 Risk adjusted comparison group GKV Average Rheumatoid Arthritis Risk adjusted comparison group GKV Average Rheumatoid Arthritis Risk adjusted comparison group GKV Average Service Area Ø Std. Ø Std. Ø Std. Ø Std. Ø Std. Ø Std. Ø Std. Ø Std. Ø Std. Ambulatory Hospital Pharmacy Remedies Utilities Other Total cost Rheumatoid Arthritis: Development of treatment cost Ambulatory Hospital Pharmacy Remedies Utilities Other Figure 20: Rheumatoid Arthritis - Development of treatment cost Page 17

19 Rheumatoid Arthritis: Prevalence Table 8: Occurence of all RA-diagnoses in 2012 by age and sex and extrapolation to Germany Sex Age group N / N Germany Female > Total Male > Total All > Total Rheumatoid Arthritis: Diagnoses per > 79 Female Male All Figure 8a: Rheumatoid Arthritis - Prevalence by sex and age groups Rheumatoid Arthritis: Prevalence in Germany > 79 Figure 8b: Rheumatoid Arthritis - Prevalence 2012 Female Male All Page 18

20 Rheumatoid Arthritis: Persistence of the RA-diagnosis in prevalent patients Table 9: Abs. and rel. frequencies of prevalent RA-diagnoses by age >= 80 Total Quarter N % N % N % N % N % N % N % N % 1 Quart ,7% ,7% ,5% ,3% 968 9,6% ,3% 617 8,4% ,0% 2 Quart ,5% ,9% ,3% 815 9,4% 830 8,3% 936 7,1% 571 7,8% ,6% 3 Quart ,7% 141 9,4% 334 7,6% 535 6,2% 598 6,0% 691 5,2% 502 6,8% ,3% 4 Quart. 70 8,8% 120 8,0% 260 5,9% 514 5,9% 580 5,8% 650 4,9% 407 5,5% ,7% 5 Quart. 49 6,2% 84 5,6% 233 5,3% 436 5,0% 437 4,4% 525 4,0% 343 4,7% ,6% 6 Quart. 53 6,7% 62 4,1% 173 4,0% 285 3,3% 307 3,1% 335 2,5% 297 4,0% ,3% 7 Quart. 32 4,0% 58 3,9% 130 3,0% 254 2,9% 271 2,7% 357 2,7% 295 4,0% ,0% 8 Quart ,4% ,4% ,4% ,0% ,3% ,2% ,8% ,5% Total ,0% ,0% ,0% ,0% ,0% ,0% ,0% ,0% 70% Rheumatoid Arthritis: Persistence of the diagnosis 60% Proportion of patients 50% 40% 30% 20% 10% >= 80 0% 1 Quart. 2 Quart. 3 Quart. 4 Quart. 5 Quart. 6 Quart. 7 Quart. 8 Quart. Figure 9: Prevalent rheumatoid arthritis - Persistence of the diagnosis by age Page 19

21 Rheumatoid Arthritis: Burden of disease compared to a risk adjusted comparison group Table 10: Different risk scores of patients having a RA-diagnosis in 2012 compared to a risk adjusted comparison group RA-diagnosis RA-diagnosis and biologics RA-diagnosis and no biologics Non-RA risk adjusted comparison group Risk factor 2,3 3,0 2,2 2,5 Charlson Score 2,6 2,2 2,7 2,3 Ø age 64,2 55,7 64,9 64,6 Ø cost Burden of disease in patients with rheumatoider arthritis Non-RA risk adjusted comparison group RA-diagnosis and no biologics RA-diagnosis and biologics RA-diagnosis 0,0 0,5 1,0 1,5 2,0 2,5 3,0 3,5 Risk factor Figure 10: Prevalent rheumatoide Arthritis - Burden of disease Page 20

22 Rheumatoid Arthritis: Active treatment within one year after selection Table 11: Abs. and rel. frequensies of active treatment by sex in the year after selection in patients presenting rheumatoid arthritis Female Male All Treatment activities N % Cost N % Cost N % Cost Age No treatment ,8% ,9% ,7% ,56 Active treatment ,2% ,1% ,3% ,90 All % 5524, % % ,59 100% Active treatment in patients presenting rheumatoide arthritis 90% 80% 70% 60% 50% 40% Active treatment No treatment 30% 20% 10% 0% weiblich männlich Figure 11: Prevalent rheumatoid arthritis: Treatment activities in the year after selction Page 21

23 Rheumatoid Arthritis: Active treatment Table 12: Number of patients presenting actively treated rheumatoid arthritis by age and sex and extrapolation to the population of Germany Female Male All Sex Age Group N /100,000 N Germany > Total > Total > Total Actively treated rheumatoid arthritis Female Male All > 79 Figure 12: Prevalent rheumatoid arthritis - Number of actively treated Page 22

24 Rheumatoid Arthritis: Prescribed drugs in the 8 quarters after selection Table 13: Abs. and rel. frequencies of drug treatment levels in prevalent patients presenting rheumatoid arthritis over 8 quarters after selection Q1 Q2 Q3 Q4 Year 1 Highest therapie level N % N % N % N % N % NSAID ,0% ,6% ,4% ,6% ,2% DMARD ,6% ,6% ,1% ,6% ,0% NSAID, DMARD ,1% ,7% ,6% ,1% ,9% Biologics ,1% ,6% ,1% ,5% ,8% NSAID, Biologics ,9% ,9% ,1% ,1% ,9% DMARD, Biologics ,4% ,1% ,3% ,8% ,6% NSAID, DMARD, Biologics ,3% ,0% ,0% ,8% ,9% Corticoids 546 2,5% 617 2,6% 668 2,6% 700 2,6% 331 0,9% Corticoids, NSAID 208 1,0% 216 0,9% 248 1,0% 253 1,0% 296 0,8% Corticoids, DMARD 415 1,9% 441 1,9% 458 1,8% 457 1,7% 366 1,0% Corticoids, NSAID, DMARD 252 1,2% 256 1,1% 266 1,0% 294 1,1% 578 1,5% Corticoids, Biologics 121 0,6% 159 0,7% 153 0,6% 174 0,7% 136 0,4% Corticoids, NSAID, Biologics 76 0,3% 66 0,3% 84 0,3% 101 0,4% 196 0,5% Corticoids, DMARD, Biologics 160 0,7% 149 0,6% 173 0,7% 184 0,7% 345 0,9% Corticoids, NSAID, DMARD, Biologics 109 0,5% 94 0,4% 115 0,5% 107 0,4% 684 1,8% One of the above % % % % % Q5 Q6 Q7 Q8 Year 2 Highest therapie level N % N % N % N % N % NSAID ,3% ,6% ,3% ,9% ,1% DMARD ,9% ,5% ,3% ,7% ,6% NSAID, DMARD ,4% ,1% ,1% ,6% ,3% Biologics ,8% ,6% ,8% ,5% ,1% NSAID, Biologics ,1% ,2% ,5% ,5% ,1% DMARD, Biologics ,8% ,0% ,9% ,0% ,4% NSAID, DMARD, Biologics ,8% ,8% ,6% ,2% ,1% Corticoids 721 2,7% 780 3,1% 784 3,1% 795 3,2% 344 0,9% Corticoids, NSAID 300 1,1% 245 1,0% 242 1,0% 256 1,0% 334 0,9% Corticoids, DMARD 491 1,9% 489 1,9% 490 1,9% 489 2,0% 426 1,1% Corticoids, NSAID, DMARD 265 1,0% 252 1,0% 267 1,1% 250 1,0% 546 1,4% Corticoids, Biologics 164 0,6% 203 0,8% 182 0,7% 196 0,8% 189 0,5% Corticoids, NSAID, Biologics 85 0,3% 98 0,4% 88 0,3% 96 0,4% 242 0,6% Corticoids, DMARD, Biologics 193 0,7% 180 0,7% 221 0,9% 202 0,8% 397 1,0% Corticoids, NSAID, DMARD, Biologics 115 0,4% 126 0,5% 125 0,5% 108 0,4% 703 1,8% One of the above % % % % % Page 23

25 All prescriptions Q1 Q2 Q3 Q4 Year 1 NSAID ,2% ,9% ,8% ,4% ,6% DMARD ,9% ,5% ,5% ,3% ,8% Corticoids ,6% ,3% ,9% ,2% ,6% Biologics ,7% ,5% ,5% ,5% ,6% Q5 Q6 Q7 Q8 Year 2 NSAID ,5% ,4% ,4% ,1% ,3% DMARD ,6% ,9% ,2% ,6% ,7% Corticoids ,0% ,4% ,2% ,8% ,8% Biologics ,9% ,4% ,4% ,6% ,3% Proportion of patients presentinga rheumatoid arthritis 60% 50% 40% 30% 20% 10% 0% Prescribed drug groups in patients presenting rheumatoid arthritis Quarters after selection NSAID DMARD Corticoids Biologics Figure 13: Prevalent rheumatoide arthritis - Prescribed drugs over 8 quarters after selection Page 24

26 Rheumatoide Arthritis: Prescription of biologics in prevalent patients 8 quarters after diagnosis Table 14a: Abs. and rel. frequencies of prevalent RA-patients with biologics prescriptions within 8 quarters after diagnosis and average cost in the index year Q1-Q8 after RA diagnosis New Terminated All Biologic n Ø cost index Ø cost index year n year n Proportion Abatacept % Adalimumab % Anakinra % Certolizumab pegol % Etanercept % Golimumab % Infliximab % Rituximab % Tocilizumab % Ustekinumab % Total % 1400 Rheumatoid Arthritis: Change in therapy and proportion of all prescribed biologics Anakinra Etanercept Termination Ustekinumab Abatacept Certolizumab Adalimumab Infliximab Golimumab pegol 0 Tocilizumab Rituximab New Prescriptions Proportion Figure 14a: Rheumatoid Arthritis: Overview of new and terminated prescription of biologics Page 25

27 Table 14b: Number of prevalent RA-patients with prescription of biologics in the two years after diagnosis Biologic Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Abatacept Adalimumab Anakinra Certolizumab pegol Etanercept Golimumab Infliximab Rituximab Tocilizumab Ustekinumab <5 < Total Rheumatoid Arthritis: Course of biologics prescriptions Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Figure 14b: Rheumatoid Arthritis - Course of biologics prescriptions Page 26

28 Table 14c: Frequencies of patients with biologics prescriptions as first, second or third line therapy Q1-Q8 after RA diagnosis First Line Second Line Third Line Biologic n Average Average cost n Average cost n cost Abatacept Adalimumab Anakinra Certolizumab pegol Etanercept Golimumab Infliximab Rituximab Tocilizumab Ustekinumab < Gesamt Gesamt Rheumatoid Arthritis: Biologics prescriptions first half-year 2015 First Line Second Line Third Line Figure 14c: Rheumatoid Arthritis: Biologics prescriptions in first half-year 2015 Page 27

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