Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials1

Webster, Angela C; Playford, E. Geoffrey; Higgins, Gail; Chapman, Jeremy R.; Craig, Jonathan C.

doi:10.1097/01.tp.0000109643.32659.c4

Cited by 216 publications

(128 citation statements)

References 28 publications

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“…On the basis of previous findings, however, patients who were exposed to less RATG were at lower risk (20). Other studies found that IL-2R antagonists do not increase the risk for lymphomas (15,44) and solid tumors (15,44), suggesting that add-on therapy with IL-2R antagonists can be relatively safe.…”

Section: Discussionmentioning

confidence: 89%

Basiliximab Combined with Low-Dose Rabbit Anti-Human Thymocyte Globulin

Ruggenenti

Codreanu²,

Cravedi³

et al. 2006

Clinical Journal of the American Society of Nephrology

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In high-risk kidney transplant recipients, induction therapy with rabbit anti-human thymocyte globulin (RATG) reduces the risk for acute rejection but is associated with significant toxicity, opportunistic infections, and cancer. Using reduced doses of RATG combined with anti-IL-2 antibodies may achieve the same antirejection activity of standard-dose RATG but with a better safety profile. This randomized, open-label study compared the efficacy, tolerability, and costs of low-dose RATG (0.5 mg/kg per d) plus basiliximab (20 mg 4 d apart) versus standard-dose RATG (2 mg/kg per d) in 33 consecutive high-risk renal transplant recipients (living-related transplant recipients, sensitized patients or patients who received another transplant, and patients with delayed graft function) over 6 mo of follow-up. All patients received concomitant therapy with steroids, cyclosporin A, and azathioprine or mycophenolate mofetil. Seventeen patients received low-dose RATG plus basiliximab, and 16 received standard-dose RATG. Patient (100 versus 100%) and graft (94 versus 100%) survival were comparable in the two groups, but the incidence of fever (17.6 versus 56.5%; P ‫؍‬ 0.01), leukopenia (23.5 versus 56.3%; P < 0.05), anemia (29.4 versus 62.5%; P < 0.05), cytomegalovirus reactivations (17.6 versus 56.5%; P ‫؍‬ 0.01), the number of transfused units (0.5 ؎ 0.9 versus 2.0 ؎ 2.4; P < 0.001), and treatment costs (3652 ؎ 704 versus 5400 ؎ 1960 euro; P ‫؍‬ 0.001) were lower with low-dose RATG plus basiliximab than with standard-dose RATG. There was one episode of biopsy-proven acute rejection on low-dose RATG plus basiliximab, and there were two on standard-dose RATG. In renal transplantation, induction therapy with basiliximab plus low-dose RATG effectively prevents acute rejection and is safer and more cost-effective than induction with standard-dose RATG.

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Section: Discussionmentioning

confidence: 89%

Basiliximab Combined with Low-Dose Rabbit Anti-Human Thymocyte Globulin

Ruggenenti

Codreanu²,

Cravedi³

et al. 2006

Clinical Journal of the American Society of Nephrology

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“…There are two chimaeric monoclonal IL-2 receptor antagonists with different pharmacokinetic features: basiliximab, with a terminal half-life of 7 d, and daclizumab, with a terminal half-life of 20 d (Kovarik et al, 1997;Vincenti et (Henry & Rajab, 2002;Van Gelder et al, 2004;Webster et al, 2004). To the best of our knowledge, there has only been one prospective trial investigating the chimaeric IL-2 receptor antagonist daclizumab in steroid-refractory aGVHD (Przepiorka et al, 2000).…”

mentioning

confidence: 99%

Efficacy of the interleukin‐2 receptor antagonist basiliximab in steroid‐refractory acute graft‐versus‐host disease

et al. 2005

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Acute graft-versus-host disease (aGVHD) occurs in up to 80% of patients who undergo allogeneic stem cell transplantation (SCT) and contributes significantly to transplant-related mortality (TRM). We conducted a prospective phase II trial to assess the efficacy and feasibility of treating steroid-refractory aGVHD with basiliximab, a chimaeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor. Basiliximab was administered intravenously at a dose of 20 mg on days 1 and 4. Twenty-three patients were enrolled between October 1999 and July 2004. We found a primary overall response rate of 82AE5% with four patients (17AE5%) showing a complete response and 15 patients (65%) a partial response. Six patients were again treated successfully with an IL-2 receptor antagonist because of recurrence of aGVHD. The rates of infections, chronic GVHD, malignancy recurrence and 1-year TRM following immunosuppression with basiliximab were comparable with those found with other treatment modalities for aGVHD. We conclude that basiliximab is efficient and feasible for steroid-refractory aGVHD and merits further evaluation.

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“…IL-2RA have shown a signifi cant reduction in BPAR as well as improved graft outcomes compared to placebo in a comprehensive Cochrane review looking at over 30 randomized controlled trials [49]. The same review also showed no increase in the incidence of malignancy although it did not show any advantage of IL-2RA in all-cause mortality.…”

Section: T-cell Non-depleting Agentsmentioning

confidence: 85%

Tailor-Made Induction Therapy in ‘Low Risk’ Renal Transplants; A South Asian Perspective

Gunawansa¹

2017

Arch Clin Nephrol

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Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials1

Abstract: Given a 40% risk of rejection, seven patients would need treatment with IL-2Ra in addition to standard therapy, to prevent one patient from undergoing rejection, with no definite improvement in graft or patient survival. There is no apparent difference between basiliximab and daclizumab.

Cited by 216 publications

References 28 publications

Basiliximab Combined with Low-Dose Rabbit Anti-Human Thymocyte Globulin

Basiliximab Combined with Low-Dose Rabbit Anti-Human Thymocyte Globulin

Efficacy of the interleukin‐2 receptor antagonist basiliximab in steroid‐refractory acute graft‐versus‐host disease

Tailor-Made Induction Therapy in ‘Low Risk’ Renal Transplants; A South Asian Perspective

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