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Pulmonary arterial hypertension in patients treated with interferon

Laurent Savale, Marie-Camille Chaumais, Olivier Sitbon, Marc Humbert
European Respiratory Journal 2015 46: 1851-1853; DOI: 10.1183/13993003.01376-2015
Laurent Savale
1AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
2INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
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  • For correspondence: laurent.savale@bct.aphp.fr
Marie-Camille Chaumais
2INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
4AP-HP, Service de pharmacie, DHU Thorax Innovation, Hôpital Antoine Béclère, Clamart, France
5Univ. Paris-Sud, Faculté de Pharmacie, Chatenay Malabry, France
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Olivier Sitbon
1AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
2INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
3Univ. Paris-Sud, Le Kremlin-Bicêtre, France
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Marc Humbert
1AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
2INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
3Univ. Paris-Sud, Le Kremlin-Bicêtre, France
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Abstract

Accumulating clinical and experimental data argue for a possible causal link between IFN therapy and PAH http://ow.ly/Ttsqv

From the authors:

We read with interest the correspondence by Prella and colleagues reporting yet another case of pulmonary arterial hypertension (PAH) suspected to be induced by long-term interferon (IFN)-β therapy in a patient with multiple sclerosis. As discussed by Prella and colleagues, IFN-α and IFN-β are regarded as “possible” risk factors for PAH [1]. This was justified by the publication of case reports of IFN-induced PAH in the past decade [2–10] and the experience recently reported by the French Referral Centre for Pulmonary Hypertension [11]. Despite strong clinical and temporal suspicion, it remains a great challenge to definitively confirm the causal role of IFN in the development PAH because many patients (especially those treated with IFN-α for hepatitis C) have concomitant PAH risk factors such as portal hypertension and/or HIV infection. In these patients, IFN therapy may potentially act as an additional trigger for portopulmonary and/or HIV-associated PAH.

In order to provide further clinical evidence to support a causal link between IFN exposure and the development of PAH, detailed analysis of IFN-induced PAH in patients without concomitant risk factors for PAH is required, together with analysis of long-term outcomes after IFN discontinuation. Thus, the case report by Prella and colleagues and two further cases published recently are very interesting. In all three cases, severe PAH suspected to be induced by IFN-β occurred in patients without other PAH risk factors [7, 8]. The analysis of disease evolution after IFN discontinuation provides additional support for a causal role of IFN. Spontaneous and complete reversal of PAH was seen in two cases [7, 8] and in the third case, near normalisation of haemodynamics occurred after 6 months of therapy with an endothelin antagonist and phosphodiesterase-5 inhibitor.

Considering these three cases, the number of PAH cases associated with IFN-α or IFN-β exposure confirmed by right heart catheterisation and reported in the literature now total 55 and 10, respectively (table 1). Interestingly, all PAH patients exposed to IFN-β were females, and clinical and functional improvements were usually observed after IFN withdrawal. However, some patients required targeted PAH treatment. Reversible PAH has only been described in patients without concomitant PAH risk factors.

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TABLE 1

Literature search for cases of pulmonary arterial hypertension (PAH) induced by interferon (IFN)-α and -β and confirmed by right heart catheterisation

As indicated previously, initiation of IFN therapy in patients with known PAH often results in clinical and functional worsening. Interestingly, PAH worsening is usually transient even in the absence of reinforcement of PAH therapy [11]. When IFN therapy is considered mandatory in a patient with PAH, we recommend a complete baseline clinical and haemodynamic assessment, optimisation of PAH treatment prior to cautious initiation of IFN treatment, and close clinical monitoring during and after IFN therapy.

Clinical experience has been recently enriched by basic science research on this topic demonstrating that IFN is involved in both human and experimental pulmonary hypertension [12]. The effects of IFN are regulated by IFN receptor 1, and could induce IP10 and endothelin-1 release leading to pulmonary endothelial dysfunction.

In conclusion, accumulating clinical and experimental data argue for a link between IFN therapy and PAH. Awareness of drug-induced PAH allows better pharmacovigilance and reporting of possible drug-induced cases. Close interactions between drug regulatory agencies, pharmaceutical companies and healthcare professionals as well as systematic reporting of potential drug-induced PAH cases are key to provide robust information to the community [13].

Footnotes

  • Conflict of interest: Disclosures can be found alongside the online version of this article at erj.ersjournals.com

  • Received August 18, 2015.
  • Accepted August 19, 2015.
  • Copyright ©ERS 2015

References

  1. ↵
    1. Simonneau G,
    2. Gatzoulis MA,
    3. Adatia I, et al.
    Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013; 62: Suppl., D34–D41.
    OpenUrlCrossRefPubMedWeb of Science
  2. ↵
    1. Fruehauf S,
    2. Steiger S,
    3. Topaly J, et al.
    Pulmonary artery hypertension during interferon-alpha therapy for chronic myelogenous leukemia. Ann Hematol 2001; 80: 308–310.
    OpenUrlCrossRefPubMedWeb of Science
    1. Jochmann N,
    2. Kiecker F,
    3. Borges AC, et al.
    Long-term therapy of interferon-α induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report. Cardiovasc Ultrasound 2005; 3: 26.
    OpenUrlCrossRefPubMed
    1. Ledinek AH,
    2. Jazbec SS,
    3. Drinovec I, et al.
    Pulmonary arterial hypertension associated with interferon β treatment for multiple sclerosis: a case report. Mult Scler 2009; 15: 885–886.
    OpenUrlAbstract/FREE Full Text
    1. Dhillon S,
    2. Kaker A,
    3. Dosanjh A, et al.
    Irreversible pulmonary hypertension associated with the use of interferon α for chronic hepatitis C. Dig Dis Sci 2010; 55: 1785–1790.
    OpenUrlCrossRefPubMed
    1. Caravita S,
    2. Secchi MB,
    3. Wu SC, et al.
    Sildenafil therapy for interferon-β-1a-induced pulmonary arterial hypertension: a case report. Cardiology 2011; 120: 187–189.
    OpenUrlCrossRefPubMedWeb of Science
  3. ↵
    1. McGovern EM,
    2. Judge EP,
    3. Kavanagh E, et al.
    Interferon β related pulmonary arterial hypertension; an emerging worrying entity? Mult Scler Relat Disord 2015; 4: 284–286.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Gibbons E,
    2. Promislow S,
    3. Davies RA, et al.
    Reversible pulmonary arterial hypertension associated with interferon-β treatment for multiple sclerosis. Can Respir J 2015; 22: 263–265.
    OpenUrlPubMed
    1. Ko T,
    2. Hatano M,
    3. Nitta D, et al.
    A case of interferon-alpha-induced pulmonary arterial hypertension after living donor liver transplantation. Heart Vessels 2015 [in press; DOI: 10.1007/s00380-015-0701-1].
  5. ↵
    1. Anderson RD,
    2. Thompson A,
    3. Burns AT
    . Pulmonary arterial hypertension associated with the use of interferon therapy for chronic hepatitis C infection complicated by extrinsic left main coronary artery compression. Intern Med J 2014; 44: 1027–1030.
    OpenUrlCrossRefPubMed
  6. ↵
    1. Savale L,
    2. Sattler C,
    3. Günther S, et al.
    Pulmonary arterial hypertension in patients treated with interferon. Eur Respir J 2014; 44: 1627–1634.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. George PM,
    2. Oliver E,
    3. Dorfmuller P, et al.
    Evidence for the involvement of type I interferon in pulmonary arterial hypertension. Circ Res 2014; 114: 677–688.
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Seferian A,
    2. Chaumais MC,
    3. Savale L, et al.
    Drugs induced pulmonary arterial hypertension. Presse Med 2013; 42: e303–e310.
    OpenUrlCrossRefPubMed
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Pulmonary arterial hypertension in patients treated with interferon
Laurent Savale, Marie-Camille Chaumais, Olivier Sitbon, Marc Humbert
European Respiratory Journal Dec 2015, 46 (6) 1851-1853; DOI: 10.1183/13993003.01376-2015

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Pulmonary arterial hypertension in patients treated with interferon
Laurent Savale, Marie-Camille Chaumais, Olivier Sitbon, Marc Humbert
European Respiratory Journal Dec 2015, 46 (6) 1851-1853; DOI: 10.1183/13993003.01376-2015
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