Format

Send to

Choose Destination
See comment in PubMed Commons below
J Heart Lung Transplant. 2015 Nov;34(11):1366-75. doi: 10.1016/j.healun.2015.05.025. Epub 2015 Jun 11.

Long-term safety and efficacy of imatinib in pulmonary arterial hypertension.

Author information

1
Baylor College of Medicine and The Lung Center at Houston Methodist Hospital, Houston, Texas. Electronic address: afrost@houstonmethodist.org.
2
College of Physicians and Surgeons, Columbia University, New York, New York.
3
Department of Respiratory Medicine, Medizinische Hochschule, and German Centre of Lung Research (DZL), Hannover, Germany.
4
Cardiology Division, Severance Cardiovascular Hospital, Yonsei University Health System, Seoul, South Korea.
5
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota.
6
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
7
Department of Specialised, Experimental, and Diagnostic Medicine, Università di Bologna, Bologna, Italy.
8
John Hopkins Bayview Medical Center, Johns Hopkins University, Baltimore, Maryland.
9
Department of Pulmonology, University Medical Centre Hamburg, Hamburg, Germany.
10
Division of Cardiology, National Hospital Organization Okayama Medical Center, Okayama, Japan.
11
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrookes and Papworth Hospitals, Cambridge, United Kingdom.
12
Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom.
13
Clinic for Internal Medicine, University of Regensburg, Regensburg, Germany.
14
Department of Pneumology and ICU, Hopital Bicetre, Paris, France.
15
Duke Pulmonary Vascular Disease Center, Duke University Medical Center, Durham, North Carolina.
16
University of Texas Southwestern Advanced Lung Disease & Lung Transplant Clinic, University of Texas Southwestern Medical Center, Dallas, Texas.
17
Department of Cardiovascular and Respiratory Disease, La Sapienza University, Rome, Italy.
18
Department of Global Clinical Development, Novartis Pharmaceuticals, East Hanover, NJ.
19
University of Giessen and Marburg Lung Center, University Hospital Giessen and Marburg GmbH, Giessen, Germany.

Abstract

BACKGROUND:

Imatinib is an oral inhibitor of several protein kinases implicated in the pathophysiology of pulmonary hypertension. Treatment with imatinib resulted in improved hemodynamics and exercise capacity in a controlled trial (Imatinib [QTI571] in Pulmonary Arterial Hypertension, a Randomized Efficacy Study [IMPRES]), among pulmonary arterial hypertension (PAH) patients inadequately responsive to 2 to 3 PAH-specific therapies.

METHODS:

The long-term (up to 204 weeks) safety and efficacy of imatinib in this open-label extension study were reviewed until early study termination on April 16, 2014. Of 202 IMPRES-enrolled patients, 66 imatinib and 78 placebo recipients entered the extension.

RESULTS:

Overall, 93.8% (135 of 144) of patients discontinued the extension study; administrative issues (i.e., sponsor termination; 32.6%) and adverse events (31.3%) were the primary reasons for discontinuation. Nine patients completed the extension study before it was terminated. Serious and unexpected adverse events were frequent. These included 6 subdural hematomas in the extension study and 17 deaths during or within 30 days of study end. Although the patients who tolerated imatinib and remained in the extension for a longer duration did experience an improvement in functional class and walk distance, most discontinued the drug and the study.

CONCLUSIONS:

Severe adverse events, significant side effects, and a high discontinuation rate limit the utility of imatinib in the treatment of PAH. These risks outweigh any possible improvements in hemodynamics and walk distance seen in those patients able to remain on drug. The off-label use of this compound in PAH is discouraged.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01392495.

KEYWORDS:

efficacy; imatinib; long-term; pulmonary arterial hypertension; safety

PMID:
26210752
DOI:
10.1016/j.healun.2015.05.025
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center