Immunosuppressive therapy for kidney transplant in adults

Basiliximab

3.1 Basiliximab (Simulect, Novartis Pharmaceuticals) is a monoclonal antibody that acts as an interleukin‑2 receptor antagonist. It has a marketing authorisation in the UK for the prophylaxis of acute organ rejection in adults having a kidney transplant. The summary of product characteristics states that basiliximab is to be used concomitantly with ciclosporin for microemulsion- and corticosteroid-based immunosuppression, in patients with panel-reactive antibodies less than 80%, or in a triple maintenance immunosuppressive regimen containing ciclosporin for microemulsion, corticosteroids and either azathioprine or mycophenolate mofetil.

3.2 Basiliximab is administered intravenously, in 2 doses of 20 mg each (one 2 hours before the surgery and the second 4 days after).

3.3 Basiliximab is available in 10‑mg and 20‑mg vials, at a price of £758.69 and £842.38 respectively (excluding VAT; British national formulary [BNF] online [accessed August 2017]), equating to £1,685 per course of treatment (2 doses of 20 mg).

Rabbit anti-human thymocyte immunoglobulin

3.4 Rabbit anti-human thymocyte immunoglobulin (r‑ATG; Thymoglobuline, Sanofi) is made by injecting human thymus cells into rabbits. The drug contains immunoglobulins (antibodies) that attach to and destroy some of the cells of the immune system. It has a marketing authorisation in the UK for the prevention of graft rejection in kidney transplant. The summary of product characteristics states that it is usually used with other immunosuppressive drugs.

3.5 r‑ATG is administered intravenously, at a dose of 1 to 1.5 mg/kg/day for 3 to 9 days after a kidney transplant (a cumulative dose of 3 to 13.5 mg/kg).

3.6 r‑ATG is available in 25 mg vials, at a price of £158.77 (excluding VAT; BNF online [accessed August 2017]), equating to £1,428.93 to £7,144.65 per course for a 70‑kg person.

Immediate-release tacrolimus

3.8 Brands of immediate-release tacrolimus include Adoport (Sandoz), Capexion (Mylan), Modigraf (Astellas Pharma), Perixis (Accord Healthcare), Prograf (Astellas Pharma), Tacni (Teva) and Vivadex (Dexcel Pharma). All of these formulations have marketing authorisations in the UK for the prophylaxis of transplant rejection in adults having a kidney transplant. Adoport, Capexion, Perixis, Prograf, Tacni and Vivadex are administered orally as capsules, twice a day. Prograf can also be administered intravenously. Modigraf consists of granules for oral suspension.

3.9 For all brands of immediate-release tacrolimus, the summary of product characteristics recommends an initial dose of 0.2 to 0.3 mg/kg/day orally or 0.05 to 0.1 mg/kg/day intravenously, and states that the dosage is usually reduced in the period after the transplant.

3.10 Modigraf (tacrolimus granules for oral suspension) is available in sachets of 0.2 mg and 1 mg at a price of £7.13 per mg (excluding VAT; BNF online [accessed August 2017]). The company has agreed a nationally available price reduction for Modigraf with the Commercial Medicines Unit. The prices agreed through the framework are commercial in confidence. Tacrolimus immediate-release capsules are available as 0.5‑mg, 0.75‑mg, 1‑mg, 2‑mg and 5‑mg capsules (depending on the brand), the price of which varies by brand. The assessment group (AG) calculated that the average cost paid by the NHS for immediate-release tacrolimus capsules is £0.52 per mg (excluding VAT; data from the Electronic Market Information Tool [eMIT], Commercial Medicines Unit). This equates to £50.96 to £76.44 per week for an initial dose of 0.2 to 0.3 mg/kg/day in a 70‑kg person. Adoport is available to the NHS with a nationally available price reduction agreed between the company and the Commercial Medicines Unit. The prices agreed through the framework are commercial in confidence.

Prolonged-release tacrolimus

3.11 Prolonged-release tacrolimus (Advagraf, Astellas Pharma) is administered orally as a capsule, once a day. It has a marketing authorisation in the UK for the prophylaxis of transplant rejection in adults having a kidney transplant. The summary of product characteristics recommends an initial dose for adults of 0.2 to 0.3 mg/kg/day. The dosage is usually reduced in the period after the transplant.

3.12 Prolonged-release tacrolimus (Advagraf) is available as 0.5‑mg, 1‑mg, 3‑mg and 5‑mg capsules, at a price of £1.07 to £1.43 per mg (excluding VAT; BNF online [accessed August 2017]). This equates to £112.11 to £210.47 per week for an initial dose of 0.2 to 0.3 mg/kg/day in a 70‑kg person. Advagraf is available to the NHS with a nationally available price reduction agreed between the company and the Commercial Medicines Unit. The prices agreed through the framework are commercial in confidence.

3.13 Another brand of prolonged-release tacrolimus, Envarsus (Chiesi), obtained a marketing authorisation after the scope for this appraisal was finalised. The brand name Envarsus was not included in the AG's search for evidence and Chiesi was not asked to submit evidence for the appraisal.

Belatacept

3.14 Belatacept (Nulojix, Bristol-Myers Squibb) is a soluble fusion protein designed to selectively inhibit CD28-mediated co-stimulation of T‑cells. Belatacept, in combination with corticosteroids and a mycophenolic acid, has a marketing authorisation in the UK for prophylaxis of graft rejection in adults having a kidney transplant. The summary of product characteristics recommends that an interleukin‑2 receptor antagonist is added to this belatacept-based regimen.

3.15 Belatacept is administered intravenously. The recommended dose is 10 mg/kg on the day of the transplant, followed by 10 mg/kg on days 5, 14, 28, 56 and 84 and then 5 mg/kg every 4 weeks from then on.

3.16 Belatacept is available in 250‑mg vials at a price of £354.52 (excluding VAT; BNF online [accessed August 2017]). For a 70‑kg person, this equates to £6,381.36 for the first 12 weeks and £709.04 every 4 weeks from week 16 onwards.

Mycophenolate mofetil

3.17 Mycophenolate mofetil (generic) has a marketing authorisation in the UK, in combination with ciclosporin and corticosteroids, for the prophylaxis of acute transplant rejection in people having a kidney transplant. It can be administered orally (capsules or an oral suspension) or intravenously, at a recommended dose of 2 g/day.

3.18 The price of mycophenolate mofetil varies by brand. The oral suspension (CellCept) is available in 175‑ml containers of 1 g/5 ml suspension at a price of £3.29 per g (excluding VAT; BNF online [accessed August 2017]). At the time of the initial committee discussion (July 2015), the average cost paid by the NHS for mycophenolate mofetil capsules was £0.38 per g (excluding VAT; data from eMIT, Commercial Medicines Unit), equating to £5.28 per week.

Mycophenolate sodium

3.19 Mycophenolate sodium (Myfortic, Novartis Pharmaceuticals), in combination with ciclosporin and corticosteroids, has a marketing authorisation in the UK for the prophylaxis of acute transplant rejection in adults having a kidney transplant. It is administered orally, at a recommended dose of 1.44 g per day.

3.20 Mycophenolate sodium is available in 180‑mg and 360‑mg tablets, at a price of £4.48 per g (excluding VAT; BNF online [accessed August 2017]), equating to £45.13 per week.

Sirolimus

3.21 Sirolimus (Rapamune, Pfizer) is an antiproliferative that blocks a protein called mammalian target of rapamycin (mTOR). It has a marketing authorisation in the UK for the prophylaxis of organ rejection in adults having a kidney transplant, who are at low to moderate immunological risk. It is recommended to be used initially with ciclosporin and corticosteroids for 2 to 3 months, and may be continued only if ciclosporin can be progressively discontinued.

3.22 Sirolimus is administered orally as a tablet or solution. The recommended dose is 6 mg initially, followed by 2 mg per day for 2 to 3 months, then adjusted to obtain blood trough levels of 4 to 12 nanograms/ml.

3.23 Sirolimus is available as 0.5‑mg, 1‑mg and 2‑mg tablets and a 1 mg/ml oral solution, at a net price of £2.71 to £4.60 per mg (excluding VAT; BNF online [accessed August 2017]), equating to £16.24 to £27.60 initially, followed by £37.90 to £64.40 per week.

Everolimus

3.24 Everolimus (Certican, Novartis Pharmaceuticals) is an antiproliferative that blocks mTOR. It has a marketing authorisation for the prophylaxis of organ rejection in adults having a kidney transplant, who are at low to moderate immunological risk. The summary of product characteristics states that everolimus should be used with ciclosporin and corticosteroids. Everolimus is administered orally at an initial dose of 1.5 mg/day.

3.25 Everolimus is available in 0.25‑mg, 0.5‑mg and 0.75‑mg tablets, at a net price of £9.90 per mg (excluding VAT; BNF online [accessed August 2017]). This equates to £103.95 per week.

3.26 Costs for all of the technologies may vary in different settings because of negotiated procurement discounts.