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Editorial |

Expanded Drug Delivery Modalities in the Treatment of Pulmonary Arterial Hypertension FREE TO VIEW

Lynette M. Brown, MD, PhD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST the following: L. B. is on the speaker’s bureau for United Therapeutics.

Intermountain Medical Center, Murray, UT

CORRESPONDENCE TO: Lynette M. Brown, MD, PhD, Intermountain Medical Center, 5121 S Cottonwood, Murray, UT 84107


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(1):3-4. doi:10.1016/j.chest.2016.03.034
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Published online

Pulmonary arterial hypertension (PAH) continues to be a complex illness with multiple therapies that are designed to alter the progressive nature of this pulmonary vascular disease. The number of approved therapies continues to expand annually. Although the sheer number of new medications adds a significant amount of complexity to the management of patients with PAH, the degree of options allows for a certain degree of therapeutic individualization.

FOR RELATED ARTICLE SEE PAGE 27

Treprostinil is a molecule that was approved for the treatment of PAH in subcutaneous and IV forms initially., Its uniqueness was partially founded on its pharmacokinetics at room temperature, which offered stability and an extended half-life. Formulations of the molecule have expanded to include subcutaneous, IV, inhaled, and oral delivery routes. Understanding of each delivery method is growing, but the longest period of experience has been with the parenteral options. Although patients may have a higher comfort level with taking oral medications, there are reports of patients with progressive symptoms never receiving parenteral prostanoid therapy, which has a proven record of efficacy. Treprostinil is clearly a viable therapeutic option in patients who would benefit from advanced therapy. Side effects of treprostinil are variable, with some effects being more related to the molecule (headache, diarrhea, and jaw pain) and others being delivery method-specific. Challenges with treprostinil delivery have included central venous catheter infections with IV delivery. Alternatively, the subcutaneous infusion method, while not routinely associated with infections, has been associated with infusion site reactions (pain, erythema, and induration). The severity of patients’ side effects with subcutaneous treprostinil is variable, but in the extreme, can be a barrier to therapy. An additional large consideration to starting parenteral prostanoid therapy is the necessity of patients and family members to manage the complexities of the medication and infusion pumps. Although most patients excel in this situation, others would benefit from a more automated delivery method when IV or subcutaneous treatment options are unacceptable to the patient, when treatment fails as a result of side effects, or when therapy is unobtainable because of a patient limitation. In this issue of CHEST, Bourge et al introduce the PAH community to the option of an implantable, programmable intravascular delivery system for treprostinil infusion.

The use of implantable pumps for medication delivery has been accomplished previously, especially in the arena of intrathecal pain control and spasticity management. The ability of these devices to improve the safety of medication delivery and patient quality of life is encouraging as the PH community follows in well-trodden footsteps of implanted pumps, such as those containing baclofen for the treatment of spasticity. Implantation of the programmer, implantation of the pump, and importantly, introduction of the novel delivery catheter to the venous system in patients with PAH will require the expanded involvement of colleagues skilled in such techniques. There will be a need for technical education of methods of catheter placement and filling of the pump reservoir that will likely slow the spread of the delivery system to treatment centers as teaching is disseminated. Furthermore, just as the specialists in intrathecal drug delivery strive to report complications, so too must practitioners of PAH remain cognoscente of potential pump-, injection-, and catheter-related complications. Specialists will need to be committed to reporting potential adverse events to facilitate method modifications and solution implementation if necessary.

The independence provided by the intravascular delivery system for treprostinil infusion will in no way belay the importance of the interaction between the practitioners of PAH and patients with PAH. Although the encumbrance of a pump, line, and infusion site is no longer present, treprostinil remains a sophisticated medication that can present emergent situations in the setting of a pump technical malfunction, overdosing, or medication supply exhaustion. Communication between patients and medical staff will remain essential, and actions will by necessity need to remain swift, especially during the initial period of adaptation to the delivery system when providers accomplished at dealing with difficulties are few.

The field of pulmonary hypertension continues to grow in therapeutic expertise. There are an ever increasing number of options for medications, and an array of delivery methods are available that allow for a tailored care plan for individual patients based on their need for therapy and their distinct capabilities. The introduction of an implantable delivery system for treprostinil offers a novel approach beyond the established IV and subcutaneous routes of administration. This system may indeed expand the availability of treprostinil to a greater number of patients. Providing patients with additional options for drug delivery expands the opportunity to provide effective treatment to patients diagnosed with PAH.

References

Enderby C.Y. .Burger C. . Medical treatment update on pulmonary arterial hypertension. Ther Adv Chronic Dis. 2015;6:264-272 [PubMed]journal. [CrossRef] [PubMed]
 
Tapson V.F. .Gomberg-Maitland M. .McLaughlin V.V. .et al Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest. 2006;129:683-688 [PubMed]journal. [CrossRef] [PubMed]
 
Simonneau G. .Barst R.J. .Galie N. .et al Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2002;165:800-804 [PubMed]journal. [CrossRef] [PubMed]
 
Farber H.W. .Miller D.P. .Meltzer L.A. .et al Treatment of patients with pulmonary arterial hypertension at the time of death or deterioration to functional class IV: insights from the REVEAL Registry. J Heart Lung Transplant. 2013;32:1114-1122 [PubMed]journal. [CrossRef] [PubMed]
 
Kallen A.J. .Lederman E. .Balaji A. .et al Bloodstream infections in patients given treatment with intravenous prostanoids. Infect Control Hosp Epidemiol. 2008;29:342-349 [PubMed]journal. [CrossRef] [PubMed]
 
Bourge R.C. .Waxman A.B. .Gomberg-Maitland M. .et al Treprostinil administered to treat pulmonary artery hypertension using a fully implantable programmable intravascular delivery system: results of the DelIVery for PAH trial. CHEST. 2016;150:27-34 [PubMed]journal
 

Figures

Tables

References

Enderby C.Y. .Burger C. . Medical treatment update on pulmonary arterial hypertension. Ther Adv Chronic Dis. 2015;6:264-272 [PubMed]journal. [CrossRef] [PubMed]
 
Tapson V.F. .Gomberg-Maitland M. .McLaughlin V.V. .et al Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest. 2006;129:683-688 [PubMed]journal. [CrossRef] [PubMed]
 
Simonneau G. .Barst R.J. .Galie N. .et al Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2002;165:800-804 [PubMed]journal. [CrossRef] [PubMed]
 
Farber H.W. .Miller D.P. .Meltzer L.A. .et al Treatment of patients with pulmonary arterial hypertension at the time of death or deterioration to functional class IV: insights from the REVEAL Registry. J Heart Lung Transplant. 2013;32:1114-1122 [PubMed]journal. [CrossRef] [PubMed]
 
Kallen A.J. .Lederman E. .Balaji A. .et al Bloodstream infections in patients given treatment with intravenous prostanoids. Infect Control Hosp Epidemiol. 2008;29:342-349 [PubMed]journal. [CrossRef] [PubMed]
 
Bourge R.C. .Waxman A.B. .Gomberg-Maitland M. .et al Treprostinil administered to treat pulmonary artery hypertension using a fully implantable programmable intravascular delivery system: results of the DelIVery for PAH trial. CHEST. 2016;150:27-34 [PubMed]journal
 
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