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Interstitial Lung Disease Associated with mTOR Inhibitors in Solid Organ Transplant Recipients: Results from a Large Phase III Clinical Trial Program of Everolimus and Review of the Literature.

Lopez P, Kohler S, Dimri S - J Transplant (2014)

Bottom Line: The event was more frequent in patients with a late switch to mTORi.In most cases, ILD was reversed after prompt mTORi discontinuation.ILD induced by mTORi is an uncommon and potentially fatal event warranting early recognition and drug discontinuation.

View Article: PubMed Central - PubMed

Affiliation: Novartis Pharma AG, Postfach, 4002 Basel, Switzerland.

ABSTRACT
Interstitial lung disease (ILD) has been reported with the use of mammalian target of rapamycin inhibitors (mTORi). The clinical and safety databases of three Phase III trials of everolimus in de novo kidney (A2309), heart (A2310), and liver (H2304) transplant recipients (TxR) were searched using a standardized MedDRA query (SMQ) search for ILD followed by a case-by-case medical evaluation. A literature search was conducted in MEDLINE and EMBASE. Out of the 1,473 de novo TxR receiving everolimus in Phase III trials, everolimus-related ILD was confirmed in six cases (one kidney, four heart, and one liver TxR) representing an incidence of 0.4%. Everolimus was discontinued in three of the four heart TxR, resulting in ILD improvement or resolution. Outcome was fatal in the kidney TxR (in whom everolimus therapy was continued) and in the liver TxR despite everolimus discontinuation. The literature review identified 57 publications on ILD in solid organ TxR receiving everolimus or sirolimus. ILD presented months or years after mTORi initiation and symptoms were nonspecific and insidious. The event was more frequent in patients with a late switch to mTORi. In most cases, ILD was reversed after prompt mTORi discontinuation. ILD induced by mTORi is an uncommon and potentially fatal event warranting early recognition and drug discontinuation.

No MeSH data available.


Related in: MedlinePlus

Literature search flow diagram.
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Related In: Results  -  Collection


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fig2: Literature search flow diagram.

Mentions: In total, 57 publications were assessed as relevant and were included in the literature review (Figure 2). Of these, 45 publications provided detailed information on 68 cases of ILD (41 kidney, 17 heart, and 10 liver transplant recipients), as summarized in Table 2. The remaining 12 publications comprised 11 which reported 95 cases of ILD but supplied only limited information on individual events (Table 3) and one letter to the editor reporting a high level of information on 34 cases.


Interstitial Lung Disease Associated with mTOR Inhibitors in Solid Organ Transplant Recipients: Results from a Large Phase III Clinical Trial Program of Everolimus and Review of the Literature.

Lopez P, Kohler S, Dimri S - J Transplant (2014)

Literature search flow diagram.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4281397&req=5

fig2: Literature search flow diagram.
Mentions: In total, 57 publications were assessed as relevant and were included in the literature review (Figure 2). Of these, 45 publications provided detailed information on 68 cases of ILD (41 kidney, 17 heart, and 10 liver transplant recipients), as summarized in Table 2. The remaining 12 publications comprised 11 which reported 95 cases of ILD but supplied only limited information on individual events (Table 3) and one letter to the editor reporting a high level of information on 34 cases.

Bottom Line: The event was more frequent in patients with a late switch to mTORi.In most cases, ILD was reversed after prompt mTORi discontinuation.ILD induced by mTORi is an uncommon and potentially fatal event warranting early recognition and drug discontinuation.

View Article: PubMed Central - PubMed

Affiliation: Novartis Pharma AG, Postfach, 4002 Basel, Switzerland.

ABSTRACT
Interstitial lung disease (ILD) has been reported with the use of mammalian target of rapamycin inhibitors (mTORi). The clinical and safety databases of three Phase III trials of everolimus in de novo kidney (A2309), heart (A2310), and liver (H2304) transplant recipients (TxR) were searched using a standardized MedDRA query (SMQ) search for ILD followed by a case-by-case medical evaluation. A literature search was conducted in MEDLINE and EMBASE. Out of the 1,473 de novo TxR receiving everolimus in Phase III trials, everolimus-related ILD was confirmed in six cases (one kidney, four heart, and one liver TxR) representing an incidence of 0.4%. Everolimus was discontinued in three of the four heart TxR, resulting in ILD improvement or resolution. Outcome was fatal in the kidney TxR (in whom everolimus therapy was continued) and in the liver TxR despite everolimus discontinuation. The literature review identified 57 publications on ILD in solid organ TxR receiving everolimus or sirolimus. ILD presented months or years after mTORi initiation and symptoms were nonspecific and insidious. The event was more frequent in patients with a late switch to mTORi. In most cases, ILD was reversed after prompt mTORi discontinuation. ILD induced by mTORi is an uncommon and potentially fatal event warranting early recognition and drug discontinuation.

No MeSH data available.


Related in: MedlinePlus