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CLAD prevention in lung transplant recipients: Tacrolimus vs cyclosporin
Diffuse Lung Disease and Lung Transplant Network
Lung Transplant Section
, accounting for around 40% of deaths.1 LTRs are typically maintained on a three-drug immunosuppressive regimen—a calcineurin inhibitor, antimetabolite agent, and corticosteroid—in order to prevent rejection. Strong randomized controlled trial-generated evidence guiding the choice of immunosuppressive therapy for LTRs is generally lacking.
A recent large, multicentered, randomized controlled trial in Scandinavia compared outcomes between once daily extended-release tacrolimus and twice daily cyclosporin.2 The target trough for cyclosporin was 250 to 300 ng/mL (0 to 3 months), 200 to 250 ng/mL (3 to 6 months), 150 to 200 ng/mL (6 to 12 months), and 100 to 150 ng/mL beyond 12 months. The trough target for tacrolimus was 10 to 14 ng/mL (0 to 3 months), 8 to 12 ng/mL (3 to 6 months), 8 to 10 ng/mL (6 to 12 months), and 6 to 8 ng/mL beyond 12 months.
The study demonstrated that immunosuppressive regimens containing tacrolimus significantly reduced incidence of CLAD diagnosis at 36 months. The cumulative incidence of CLAD was 39% in the cyclosporin group vs 13% in the tacrolimus group (P < .0001), and the number needed to treat was 3.9 patients to prevent one case of CLAD with tacrolimus. While mortality was not significantly different between the two treatment groups in the intention to treat models, tacrolimus had a mortality benefit in the per protocol analysis.
While there is no consensus guideline recommending a first-line immunosuppression regimen following lung transplantation, the lung transplant steering committee believes that additional trials comparing existing agents are of critical importance to reduce CLAD incidence and improve long-term outcomes in LTRs.
References
1. Verleden GM, et al. J Heart Lung Transplant. 2019;38(5):493-503.
2. Dellgren G, et al. Lancet Respir Med. 2024;12(1):34-44.
Diffuse Lung Disease and Lung Transplant Network
Lung Transplant Section
, accounting for around 40% of deaths.1 LTRs are typically maintained on a three-drug immunosuppressive regimen—a calcineurin inhibitor, antimetabolite agent, and corticosteroid—in order to prevent rejection. Strong randomized controlled trial-generated evidence guiding the choice of immunosuppressive therapy for LTRs is generally lacking.
A recent large, multicentered, randomized controlled trial in Scandinavia compared outcomes between once daily extended-release tacrolimus and twice daily cyclosporin.2 The target trough for cyclosporin was 250 to 300 ng/mL (0 to 3 months), 200 to 250 ng/mL (3 to 6 months), 150 to 200 ng/mL (6 to 12 months), and 100 to 150 ng/mL beyond 12 months. The trough target for tacrolimus was 10 to 14 ng/mL (0 to 3 months), 8 to 12 ng/mL (3 to 6 months), 8 to 10 ng/mL (6 to 12 months), and 6 to 8 ng/mL beyond 12 months.
The study demonstrated that immunosuppressive regimens containing tacrolimus significantly reduced incidence of CLAD diagnosis at 36 months. The cumulative incidence of CLAD was 39% in the cyclosporin group vs 13% in the tacrolimus group (P < .0001), and the number needed to treat was 3.9 patients to prevent one case of CLAD with tacrolimus. While mortality was not significantly different between the two treatment groups in the intention to treat models, tacrolimus had a mortality benefit in the per protocol analysis.
While there is no consensus guideline recommending a first-line immunosuppression regimen following lung transplantation, the lung transplant steering committee believes that additional trials comparing existing agents are of critical importance to reduce CLAD incidence and improve long-term outcomes in LTRs.
References
1. Verleden GM, et al. J Heart Lung Transplant. 2019;38(5):493-503.
2. Dellgren G, et al. Lancet Respir Med. 2024;12(1):34-44.
Diffuse Lung Disease and Lung Transplant Network
Lung Transplant Section
, accounting for around 40% of deaths.1 LTRs are typically maintained on a three-drug immunosuppressive regimen—a calcineurin inhibitor, antimetabolite agent, and corticosteroid—in order to prevent rejection. Strong randomized controlled trial-generated evidence guiding the choice of immunosuppressive therapy for LTRs is generally lacking.
A recent large, multicentered, randomized controlled trial in Scandinavia compared outcomes between once daily extended-release tacrolimus and twice daily cyclosporin.2 The target trough for cyclosporin was 250 to 300 ng/mL (0 to 3 months), 200 to 250 ng/mL (3 to 6 months), 150 to 200 ng/mL (6 to 12 months), and 100 to 150 ng/mL beyond 12 months. The trough target for tacrolimus was 10 to 14 ng/mL (0 to 3 months), 8 to 12 ng/mL (3 to 6 months), 8 to 10 ng/mL (6 to 12 months), and 6 to 8 ng/mL beyond 12 months.
The study demonstrated that immunosuppressive regimens containing tacrolimus significantly reduced incidence of CLAD diagnosis at 36 months. The cumulative incidence of CLAD was 39% in the cyclosporin group vs 13% in the tacrolimus group (P < .0001), and the number needed to treat was 3.9 patients to prevent one case of CLAD with tacrolimus. While mortality was not significantly different between the two treatment groups in the intention to treat models, tacrolimus had a mortality benefit in the per protocol analysis.
While there is no consensus guideline recommending a first-line immunosuppression regimen following lung transplantation, the lung transplant steering committee believes that additional trials comparing existing agents are of critical importance to reduce CLAD incidence and improve long-term outcomes in LTRs.
References
1. Verleden GM, et al. J Heart Lung Transplant. 2019;38(5):493-503.
2. Dellgren G, et al. Lancet Respir Med. 2024;12(1):34-44.