Moderator Harrison (Hap) Farber, MD - PowerPoint Presentation

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ModeratorHarrison (Hap) Farber, MDProfessor of MedicineDirector Pulmonary Hypertension CenterBoston University/Boston Medical CenterBoston, Massachusetts

The Health Economics of PAH

Panelists

R. James White, MD, PhD

Associate Professor of Medicine

Pharmacology and Physiology

University of Rochester School of Medicine

Rochester, New York

PAH Diagnostic WorkupGeneral Considerationsa,b

Presentation/history suggestive of PHEchocardiogram ECG, chest radiograph, TTE, PFT, HRCTV/Q scanRHCPresence of comorbidities (eg, diabetes, obesity, CAD); echocardiogram suggestive of PH  diastolic dysfunction?Initiate empiric loop diureticsSleep study  undiagnosed sleep apnea?

a.

Galie

N, et al.

Eur

Heart J

. 2009;30:2493-2537

[2]

; b.

McGoon

et al

.

Chest

.

2004;126(1

s

uppl

):14S-34S

.

[3]

When to Perform an RHC?a,b

Patient responding to empiric therapy: loop diuretics, apnea therapy?Yes  no further testing (ie, probable diastolic dysfunction)No  comprehensive guideline-recommended workup vs immediate RHC?Prior history and diagnostic workup (ie, referral population)Rule out left heart disease, sleep apneaImmediate RHC is more cost-effective vs complete workupc mPAP ≥ 25 mm Hg; PWP ≤ 15 mm Hg  proceed with guideline-directed workup

a.

Galie

N, et al.

Eur

Heart J

. 2009;30:2493-2537

[2]

; b.

McGoon

et al

.

Chest

.

2004;126(1

s

uppl

):14S-

34S

[3]

; c. Taylor B, et al

.

J Heart Lung Transplant

.

2013;32:137-138.

[1]

Cost of Hospitalizations in PAH Registry and Trial Data

REVEAL RegistryaMean total hospital days in the year after first admission for all pts with ≥ 1 hospitalization: 15.3 days (median: 7.0 days)Estimated 2012 total costs (inpatient and outpatient) for PAH: $188 million Estimated average cost/hospitalizationb ~ $60,000-$100,000 (average 3-night stay on telemetry unit)AMBITION datacNNT to prevent 1 hospitalization: 9 QALY: ~ $90,000-$100,000 or higher for longer hospital stays?Combination therapy for shorter, less intense hospitalizations?

a. Burger CD, et al

.

Chest

.

2014;146:1263

-

1273

[4]

; b. Johnson S, et al.

J Med Econ

. 2013;16:1414-1422

[5]

; c.

Gali

è

N. ERS 2014. Abstract 2916.

[6]

PAH Inpatient Management

EchocardiogramRHCCT scanIV inotropes, prostacyclinsAnticoagulantsSupplemental oxygen, CPAPContinuous monitoring

McGoon

M, et al.

Mayo

Clin

Proc

.

2009;84:

191-207

.

[3]

Reducing HospitalizationsImpact of Current and Emerging Therapies

Macitentan (ERA): SERAPHIN triala,bIncluded pts on macitentan mono- and combination therapy (PDE-5 inhibitors, oral or inhaled prostanoids, CCBs, l-arginine)Macitentan reduced primary end point (composite of death, atrial septostomy, lung transplantation, initiation of treatment with IV or SC prostanoids, worsening PAH) by 30%-45% (dose dependent; P = .01; P < .001)Reduced all-cause hospitalization by 32% (HR, 0.677; P = .0051)

Ambrisentan (ERA) ± tadalafil (PDE-5 inhibitor) vs monotherapy: AMBITION TrialcReduced clinical failure events by 50% (HR, 0.502; P = .0002); superior to each individual monotherapy (P < .01)  main treatment effect driven by hospitalizationsSelexipag (selective IP receptor agonist): GRIPHON top-line datad80% of pts receiving oral PAH therapy at onsetReduced morbidity/mortality event vs placebo by 39% (P < .0001)

a.

Pulido

T, et al.

N Engl J Med

. 2013;369:809-818

[8]

; b. Mehta S, et al. ATS 2014. Abstract B17

[9]

; c.

Galiè

N

, et al. ERS 2014. Abstract 2916

[6]

; d.

Actelion

press

release.

[10]

Early, Aggressive PAH Therapy Effect on Outcomes

Hospitalization NumberDurationUtilization of resourcesPatient satisfaction/QOLHospital-acquired infections/conditionsMorbidity and mortality events

a.

Pulido

T, et al.

N Engl J Med

. 2013;369:809-818

[8]

; b. Mehta S, et al. ATS 2014. Abstract B17

[9]

; c.

Gali

è

N, et al. ERS 2014. Abstract 2916

[6]

; d.

Actelion

press release [website].

[10]

The Real Cost of PAH Drugs Oral Treprostinila,b

History of expensive PAH drugsIV epoprostenol/SC treprostinil: ~ $90,000/yearBosentan: ~ $80,000/yearAmbrisentan: ~ $80,000/yearOral treprostinil~ $500,000/year [12 mg, three times daily  patients transitioning from parenteral treprostinil (ongoing trialc)]Compared with placebo: improved 6MWD, Borg dyspnea score (intent-to-treat population  26.0 m; P = .0001)d

a. McLaughlin VV, et al.

Circulation

. 2009;119:2250-2294

[11]

; b.

Frumkin

LR, et al

.

Pharmacol

Rev.

2012;64(3

):

583-620.

[12]

; c. White RJ, et al. ATS 2013. Abstract B64.

[13]

;

d

.

Jing ZC, et al.

Circulation

.

2013;127:624-633

[14]

The Real Cost of PAH DrugsRiociguat

Soluble guanylate cyclase stimulatorPATENT-1, randomized, phase 2 trial (PAH)aSignificant improvement 6MWDPVR (P < .001)NT-proBNP levels (P < .001)WHO FC (P = .003)TTCW (P = .005)Borg dyspnea score (P = .002)CHEST-1, randomized, phase 3 trial (CTEPH)bSignificant improvement inPVR (P < .001)NT-proBNP level (P < .001) WHO FC (P = .003)Cost: $7500/monthcCompared with tadalafil or generic sildenafil ($10,000-$12,000/year)d

a. Ghofrani

HA, et al.

N Engl J Med.

2013;369:330-340

[14]

; b

. Ghofrani HA, et al.

N Engl J Med

.

2013;369:319-329

[16]

; c. Walker T.

Drug

Topics

. October 10, 2013

[17]

; d.

McLaughlin VV, et al.

Circulation

.

2009;119:

2250-2294

.

[11]

Conclusions

Cost-effectiveness of PAH therapies will continue to be an issue, despite their improving efficacy

Efficacy, tolerability, and ease of use have to be balanced with costs to payers (

ie

, insurers, employers, government agencies)

Abbreviations

6MWD = 6-minute walk distance

CAD = coronary artery disease

CCB = calcium channel blocker

CPAP = continuous positive airway pressure

CT = computed tomography

CTEPH = chronic thromboembolic pulmonary hypertension

ECG = echocardiogram

ERA =

endothelin

receptor antagonist

FDA = US Food and Drug Administration

HR = hazard ratio

HRCT = high-resolution computer tomography

IP = intraperitoneal

mPAP

= mean pulmonary artery pressure

NNT = number needed to treat

NT-

proBNP

= N-terminal pro-brain natriuretic peptide

PAH = pulmonary arterial hypertension

PFT = pulmonary function test

PH = pulmonary

hypertension

Abbreviations (cont)

PVR

= pulse volume recording

QALY = quality-adjusted life-year

QOL = quality of life

RHC = right heart catheterization

SC = subcutaneous

TTCW = time to clinical worsening

TTE = transthoracic echocardiogram

WHO FC = World Health Organization functional class

References

1. Taylor B,

Rumbak

M, Taylor SP, Solomon D. Early versus delayed right heart catheterization in evaluation of pulmonary arterial hypertension.

J Heart Lung

Transplant. 2013;32:137-138.

2.

Galiè

N,

Hoeper

MM,

Humbert

M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT).

Eur

Heart J

. 2009;30:2493-2537.

3.

McGoon

M,

Gutterman

D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.

Chest

. 2004;126(1

suppl

):14S-34S.

4. Burger CD, Long PK, Shah MR, et al. Characterization of first-time hospitalizations in patients with newly diagnosed pulmonary arterial hypertension in the REVEAL registry.

Chest

. 2014;146:1263-1273.

References (cont)

5

. Johnson S, Delate T,

Boka

A, et al. Characterizing the financial burden of pulmonary arterial hypertension within an integrated healthcare delivery system.

J Med Econ

. 2013;16:1414-1422.

6.

Galiè

N. The AMBITION study: design and results. Presented at: 2014 European Respiratory Society Annual Meeting; June 9-14, 2014; Munich, Germany. Abstract 2916.

7.

McGoon

MD, Kane GC. Pulmonary hypertension: diagnosis and management.

Mayo Clin Proc

. 2009;84:191-207.

8. Pulido T,

Adzerikho

I,

Channick

RN, et al.

Macitentan

and morbidity and mortality in pulmonary arterial hypertension.

N

Engl

J Med

. 2013;369:809-818.

9. Mehta S,

Delcroix

M,

Galiè

N, et al.

Macitentan

reduced all-cause hospitalizations in patients with pulmonary arterial hypertension: data from the randomized controlled SERAPHIN trial. Presented at: 2014 American Thoracic Society Annual Meeting; May 16-21, 2014; San Diego, CA. Abstract A2458.

References (cont)

10

.

Actelion

press release.

Selexipag

meets primary endpoint in pivotal phase III GRIPHON outcome study in patients with pulmonary arterial hypertension. http://www1.actelion.com/en/our-company/news-and-events.page?newsId=1793163. Accessed December 15, 2014.

11. McLaughlin VV, Archer SL,

Badesch

DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association.

Circulation

. 2009;119:2250-2294

.

12.

Frumkin

LR. The pharmacological treatment of pulmonary arterial hypertension.

Pharmacol

Rev

. 2012;64(3):583-620.

13.

Jing ZC, Parikh K, Pulido T, et al. Efficacy and safety of oral

treprostinil

monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial.

Circulation

. 2013;127:624-633.

References (cont)

14.

White RJ,

Chakinala

MM,

Mathier

M, et al. Safety and tolerability of transitioning from parenteral

treprostinil

to oral

treprostinil

in patients with pulmonary arterial hypertension. Presented at: 2013 American Thoracic Society Annual Meeting; May 17-23, 2013; Philadelphia, PA. Abstract A3303.

15.

Ghofrani

HA,

Galiè

N,

Grimminger

F, et al.

Riociguat

for the treatment of pulmonary arterial hypertension.

N

Engl

J Med

. 2013;369:330-340.

16.

Ghofrani

HA,

D'Armini

AM,

Grimminger

F, et al.

Riociguat

for the treatment of chronic thromboembolic pulmonary hypertension.

N

Engl

J Med

. 2013;369:319-329.

17.

Walker T. FDA approves first drug to treat two forms of pulmonary hypertension. Drug Topics. October 10, 2013. http://drugtopics.modernmedicine.com/drug-topics/content/clinical/clinical-pharmacology/fda-approves-first-drug-treat-two-forms-pulmonary?page=full. Accessed December 15, 2013.