Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation

Sangeeta Bhorade, Vivek N. Ahya, Maher A. Baz, Vincent G. Valentine, Selim M. Arcasoy, Robert B. Love, Harish Seethamraju, Charles G. Alex, Remzi Bag, Nilto C. DeOliveira, Aliya Husain, Wickii T. Vigneswaran, Jeff Charbeneau, Jerry A. Krishnan, Ramon Durazo-Arvizu, Lourdes Norwick, Edward Garrity

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Rationale: Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, longterm survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation. Objectives: To determine the potential benefit versus risk of sirolimus in lung transplantation. Methods: We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups. Measurements and Main Results: One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infectionwas decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95% confidence interval, 0.55, 0.82]; P< 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64%) compared with AZA (49%) during the course of this study. Conclusions: Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).

Original languageEnglish (US)
Pages (from-to)379-387
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume183
Issue number3
DOIs
StatePublished - Feb 1 2011

Fingerprint

Lung Transplantation
Azathioprine
Tacrolimus
Sirolimus
Immunosuppressive Agents
Incidence
Transplantation
Graft Survival
Heart Transplantation
Cytomegalovirus
Kidney Transplantation
Lung Diseases
Randomized Controlled Trials
Clinical Trials
Confidence Intervals
Survival

Keywords

  • Lung transplantation
  • Sirolimus
  • Tacrolimus

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation. / Bhorade, Sangeeta; Ahya, Vivek N.; Baz, Maher A.; Valentine, Vincent G.; Arcasoy, Selim M.; Love, Robert B.; Seethamraju, Harish; Alex, Charles G.; Bag, Remzi; DeOliveira, Nilto C.; Husain, Aliya; Vigneswaran, Wickii T.; Charbeneau, Jeff; Krishnan, Jerry A.; Durazo-Arvizu, Ramon; Norwick, Lourdes; Garrity, Edward.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 183, No. 3, 01.02.2011, p. 379-387.

Research output: Contribution to journalArticle

Bhorade, S, Ahya, VN, Baz, MA, Valentine, VG, Arcasoy, SM, Love, RB, Seethamraju, H, Alex, CG, Bag, R, DeOliveira, NC, Husain, A, Vigneswaran, WT, Charbeneau, J, Krishnan, JA, Durazo-Arvizu, R, Norwick, L & Garrity, E 2011, 'Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation', American Journal of Respiratory and Critical Care Medicine, vol. 183, no. 3, pp. 379-387. https://doi.org/10.1164/rccm.201005-0775OC
Bhorade, Sangeeta ; Ahya, Vivek N. ; Baz, Maher A. ; Valentine, Vincent G. ; Arcasoy, Selim M. ; Love, Robert B. ; Seethamraju, Harish ; Alex, Charles G. ; Bag, Remzi ; DeOliveira, Nilto C. ; Husain, Aliya ; Vigneswaran, Wickii T. ; Charbeneau, Jeff ; Krishnan, Jerry A. ; Durazo-Arvizu, Ramon ; Norwick, Lourdes ; Garrity, Edward. / Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation. In: American Journal of Respiratory and Critical Care Medicine. 2011 ; Vol. 183, No. 3. pp. 379-387.
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abstract = "Rationale: Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, longterm survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation. Objectives: To determine the potential benefit versus risk of sirolimus in lung transplantation. Methods: We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups. Measurements and Main Results: One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infectionwas decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95{\%} confidence interval, 0.55, 0.82]; P< 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64{\%}) compared with AZA (49{\%}) during the course of this study. Conclusions: Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).",
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AU - Valentine, Vincent G.

AU - Arcasoy, Selim M.

AU - Love, Robert B.

AU - Seethamraju, Harish

AU - Alex, Charles G.

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AU - DeOliveira, Nilto C.

AU - Husain, Aliya

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AU - Norwick, Lourdes

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N2 - Rationale: Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, longterm survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation. Objectives: To determine the potential benefit versus risk of sirolimus in lung transplantation. Methods: We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups. Measurements and Main Results: One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infectionwas decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95% confidence interval, 0.55, 0.82]; P< 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64%) compared with AZA (49%) during the course of this study. Conclusions: Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).

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