Annual Prevalence and Treatment Estimates of Nontuberculous Mycobacterial Pulmonary Disease in Germany: A NTM-NET Collaborative Study Dirk Wagner KIT

Annual Prevalence and Treatment Estimates of Nontuberculous Mycobacterial Pulmonary Disease in Germany: A NTM-NET Collaborative Study Wagner, D. 1, Lange, B. 1, Kern, W.V. 1, Gallagher, J.R. 2, Gupta, R. 3, Lange, C Abteilung Infektiologie, Universitätsklinikum Freiburg, Freiburg, Deutschland 2. Clarity Research Pharma LLC, Spartanburg, SC, Vereinigte Staaten von Amerika 3. Insmed Incorporated, Monmouth Junction, NJ, Vereinigte Staaten von Amerika 4. Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Deutschland

Unterschiedliche geographische Verteilung von respiratorischen NTM-Isolaten W. Hoefsloot,…, D. Wagner for NTM-NET The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: A NTM-NET collaborative study. Eur Respir J

Die NTM- Epidemiologie ändert sich im zeitlichen Verlauf Queensland, Australien: Thompson et al Changing Epidemiology of Pulmonary Nontuberculous Mycobacteria Infections. EID 16 (10),

Niederlande v. Ingen, Wagner (2011) Epidemiology of Nontuberculous Mycobacterial Diseases in Germany and worldwide. Der Pneumologe 8(6): Die NTM- Epidemiologie ändert sich im zeitlichen Verlauf

In D steigt die Rate von stationär behandelten pulmonalen NTM-Erkrankungen Ringshausen FC, Apel RM, Bange FC, de Roux A, Pletz MW, Rademacher J, Suhling H, Wagner D, Welte T. Burden and trends of hos- pitalisations associated with pulmonary non-tuberculous mycobacterial infections in Germany, BMC Infect Dis. 2013;13:231. annual age-adjusted hospitalisation rate of pulmonary non-tuberculous mycobacterial infection as any hospital discharge diagnoses

NTMPD US, EU5 & Japan Patient Records Research Study Conducted by Clarity Pharma Research US: Q Q EU5 & Japan: Q with help of the

NTMPD US, EU5 & Japan Patient Records Research Study Conducted by Clarity Pharma Research US: Q Q EU5 & Japan: Q EU5 Deutschland Frankreich Großbritannien Italien Spanien

Ziele  Verlässliche Schätzungen  Zahl an Patienten mit NTMPD, die durch Hausärzte (Internisten /Allgemeinmediziner), Pneumologen, Infektiologen oder andere Spezialisten gesehen werden  Gesamtzahl der jeweiligen Ärzte, die NTMPD-Patienten im letzten Jahr sahen oder behandelten  Inzidenz und Prävalenz der Patienten mit NTMPD sowie mit MAC-PD und M. abscessus PD;  Zahl an Patienten mit NTMPD, die von Ärzten im letzten Jahr betreut wurden  Zahl an Patienten mit NTMPD, die von Ärzten im letzten Jahr diagnostiziert wurden  Zahl an jährlich behandelten Patienten mit NTMPD mit der jeweiligen Behandlungsmodalität  Anzahl der diagnostizierten unbehandelten Patienten

Methoden 1.NTMPD Patienten, die jährlich diagnostiziert werden, basiert auf Schätzungen aufgrund einer 2-stufigen Delphi-Befragung. 2.Eine repräsentatives Schnittmenge von Ärzten extrahierten Behandlungsinformationen aus Patientenakten mit NTMPD mit bestätigter Diagnose einer pulmonalen Mycobacterium avium complex (MAC)- oder M. abscessus- Erkrankung

Methoden 1: 2 stufige Delphi-Befragung Aim: To obtain the most accurate annual NTMPD annual prevalence estimates for EU5 countries and Japan. Method: a collaborative estimating methodology that combines independent analysis with maximum use of feedback for building consensus among experts who interact anonymously. Experts: 6 NTM experts from Europe and Japan;  Widely recognized in the scientific community;  Collectively published more than 100 scientific articles relating to NTM prevalence. Round 1: Each participant received a form via requesting the expert’s estimate of the:  Annual NTMPD prevalence rate for each of the six target countries;  Most likely annual prevalence range;  Comments/rationale for each estimate.  Analysis: Round 1 responses were analyzed. Round 2: Each panel member was provided with the mean, median, range, and other descriptive statistics of the panel’s collective prevalence estimates for each of the six countries.  Panel members revised their earlier answers in light of the collective replies of their colleagues on the panel or stated why they did not wish to change them.  Analysis and Reporting: Round 2 responses were analyzed and reported to the team for comment; no further changes were suggested.

Ergebnis Delphi-Methode: Geschätzte jährliche Prävalenz der pulmonalen NTM-Erkrankungen (NTMPD) in Deutschland: Land oder Region 2013 Bevölkerung 1 Jährliche NTMPD Prävalenz 2 (Bev/100,000) Standard Abweichung der Prävalenz Schätzung (Bev/100,000) Deutschland 82,656, If you want to know more: Come to the ERS, 7. Sep. 2014, Hall B2-29, Session 12:50-14:40 Land oder Region 2013 Bevölkerung 1 Geschätzte Zahl an NTMPD Patienten (# der Patienten) Standard Abweichung der geschätzten Zahl an NTMPD Patienten (# der Patienten) Deutschland82,656, ± 992

Ärztekontakte (EU5+Japan) Phase 1: Survey, welche Ärzte diagnostizieren und behandeln NTM-PD Patienten Phase 2: Fragebogen bzgl. Behandlungen von NTM-PD- Patienten  Number of Questions? 3%

Methoden 2: Repräsentative Ärzte Physicians in region. We determined the number of patient-care physicians in each region of each study country from the Healthcare indicators file for 2008 of the Organisation for Economic Co- operation and Development (OECD). (We label this step - A) NTMPD-treating physicians in region. From our Phase 1 study of physicians in target specialties, we determined the percentage of study physicians in each region who saw at least one NTMPD- diagnosed patient during the past 12 months. (B)

Methoden 2: Patientenzahlen Typical number of NTMPD-diagnosed patients seen per physician. We estimated the median number of NTMPD- diagnosed patients seen by physicians in the region during the past 12 months from the physician self-estimates in both phases of the study. (C) Proportion of country’s NTMPD patients in region. We determined the percentage of countrywide NTMPD patients in a region by dividing the NTMPD Patient Index for the region (product of A x B x C) by the total Patient Index sum for the country. Estimate of total NTMPD patients in region. We estimated the number of diagnosed NTMPD patients seen during the past 12 months by multiplying the region’s national proportion of NTMPD- diagnosed patients (immediate step above) by the corresponding estimated countrywide total number of NTMPD patients (derived from the Delphi process).

Ergebnis: NTMPD gibt es weniger im Norden oder Süden der Republik S5. In what country do you primarily practice medicine? S5a. In what region? S9. In the past 12 months, how many patients have you managed with confirmed diagnoses of NTMPD for the purpose of managing the care of their NTMPD? These figures are derived from physicians’ responses to s9 and s5 and estimated annual national prevalence rates from the Delphi panel. Total = est. 5,372 patients % = proportion of NTMPD patients in country 37% 21% 31% 11% Bonn  Berlin Die geschätzte jährliche NTMPD Prävalenzrate ist im Osten mit 8,2 am höchsten, die meisten Patienten (1976) leben im Westen. Der Norden hat die wenigsten NTMPD-Patienten, der Süden die niedrigste jährliche Prävalenzrate. MAP OUTLINE: PRESENTATIONMAGAZINE.COM

17 Germany Spain Italy UK Japan France MAC only (80%) n=169 M. abscessus only (14%) n=30 Diagnosed with NTMPD (100%) n=211 NTMPD treated (63%) n=132 NTMPD not treated (37%) n=79 Treated with oral antibiotics (80%) n=106 Future treatment planned (45%) n=35 Treated with inhaled antibiotics (8%) n=11 9% Treatment regimen was changed PUD IM GM Other Diagnosing physician Setting(s) in which prescribed * *Some patients prescribed antibiotic in both settings Severity at first presentation (n=12) Relative odds of treatment when other tested factors equal Treated MAC patients (93%) n=123 MAC patients treated with 3-drug macrolide regimen** for ≥ 6 months (4%) n=5 **Either clarithromycin or azithromycin and rifamycin and ethambutol If you want to know more: Come to the ERS, 7. Sep. 2014, Hall B2-29, Session 12:50-14:40 Results: Treatment patterns in Germany

Pulmonale NTM Infektionen  ATS-Behandlungsrichtlinien 2007  Adhärenz  Bekanntheitsgrad  Weiterbildung! Griffith et al Am J Respir Crit Care Med –416. Diskussion