Paroxysmal nocturnal hemoglobinuria (PNH)

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Shruti Chaturvedi, MBBS, MSCI
Baltimore, MD

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Benjamin Tillman, MD
Nashville, TN
1 regimens on this page
4 variants on this page


All lines of therapy

Eculizumab monotherapy

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Variant #1, 12-week course

Study Evidence
Hillmen et al. 2004 Pilot, <20 pts

Therapy

  • Eculizumab (Soliris) as follows:
    • Weeks 1 to 4: 600 mg IV over 25 to 45 minutes once per week
    • Weeks 5 to 12: 900 mg IV over 25 to 45 minutes once every 2 weeks

12-week course

Variant #2, 6-month course

Study Evidence Comparator Efficacy
Hillmen et al. 2006 (TRIUMPH) Phase III (E) Placebo Superior stabilization of Hgb levels and QoL

Therapy

  • Eculizumab (Soliris) as follows:
    • Weeks 1 to 4: 600 mg IV over 25 to 45 minutes once per week
    • Weeks 5 to 26: 900 mg IV over 25 to 45 minutes once every 2 weeks

Supportive medications

  • Patients received Neisseria meningitidis meningococcal vaccination

26-week course

Variant #3, 12-month course

Study Evidence
Brodsky et al. 2007 (SHEPHERD) Phase II

Therapy

  • Eculizumab (Soliris) as follows:
    • Weeks 1 to 4: 600 mg IV over 25 to 45 minutes once per week
    • Weeks 5 to 52: 900 mg IV over 25 to 45 minutes once every 2 weeks

52-week course

Variant #4, indefinite

Study Evidence
Kelly et al. 2011 Non-randomized

Initial therapy

  • Eculizumab (Soliris) as follows:
    • Weeks 1 to 4: 600 mg IV over at least 30 minutes once per day on days 1, 8, 15, 22
    • Week 5 onwards: 900 mg IV over at least 30 minutes once every 2 weeks
      • Patients with return of PNH symptoms, such as red or black urine, abdominal discomfort, or increased LDH before the next dose of eculizumab received higher doses: Eculizumab (Soliris) 1200 mg IV once every 2 weeks

Supportive medications

  • Patients received Neisseria meningitidis meningococcal vaccination
  • Penicillin V 500 mg PO BID as prophylaxis
    • Patients with penicillin allergies instead received: Erythromycin 500 mg PO BID

Given indefinitely

References

  1. Hillmen P, Hall C, Marsh JC, Elebute M, Bombara MP, Petro BE, Cullen MJ, Richards SJ, Rollins SA, Mojcik CF, Rother RP. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004 Feb 5;350(6):552-9. link to original article contains verified protocol PubMed
    1. Update: Hill A, Hillmen P, Richards SJ, Elebute D, Marsh JC, Chan J, Mojcik CF, Rother RP. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood. 2005 Oct 1;106(7):2559-65. Epub 2005 Jun 28. link to original article PubMed
  2. TRIUMPH: Hillmen P, Young NS, Schubert J, Brodsky RA, Socié G, Muus P, Röth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233-43. link to original article contains verified protocol PubMed
    1. Update: Hillmen P, Muus P, Dührsen U, Risitano AM, Schubert J, Luzzatto L, Schrezenmeier H, Szer J, Brodsky RA, Hill A, Socié G, Bessler M, Rollins SA, Bell L, Rother RP, Young NS. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007 Dec 1;110(12):4123-8. Epub 2007 Aug 16. link to original article PubMed
  3. SHEPHERD: Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, Gaya A, Coyle L, de Castro C, Fu CL, Maciejewski JP, Bessler M, Kroon HA, Rother RP, Hillmen P. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008 Feb 15;111(4):1840-7. Epub 2007 Nov 30. link to original article contains verified protocol PubMed
    1. Update: Hillmen P, Muus P, Röth A, Elebute MO, Risitano AM, Schrezenmeier H, Szer J, Browne P, Maciejewski JP, Schubert J, Urbano-Ispizua A, de Castro C, Socié G, Brodsky RA. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013 Jul;162(1):62-73. Epub 2013 Apr 25. link to original article link to PMC article PubMed
  4. Kelly RJ, Hill A, Arnold LM, Brooksbank GL, Richards SJ, Cullen M, Mitchell LD, Cohen DR, Gregory WM, Hillmen P. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011 Jun 23;117(25):6786-92. Epub 2011 Apr 1. link to original article contains verified protocol PubMed content property of HemOnc.org
    1. Update: Abstract: Anita Hill; Richard J Kelly; Austin G Kulasekararaj; Shreyans A Gandhi; Lindsay D Mitchell; Modupe Elebute; Stephen John Richards; Matthew Cullen; Louise M Arnold; Joanna Large; Alexandra Wood; Gemma L Brooksbank; Tracy Downing; Claire McKinley; Dena Cohen; Walter M Gregory; Judith C. W. Marsh; Ghulam J. Mufti; Peter Hillmen. Eculizumab in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Report of All 153 Patients Treated in the UK. 2012 ASH Annual Meeting abstract 3472. link to abstract
  5. Retrospective: Kelly RJ, Höchsmann B, Szer J, Kulasekararaj A, de Guibert S, Röth A, Weitz IC, Armstrong E, Risitano AM, Patriquin CJ, Terriou L, Muus P, Hill A, Turner MP, Schrezenmeier H, Peffault de Latour R. Eculizumab in pregnant patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2015 Sep 10;373(11):1032-1039. link to original article PubMed

Placebo

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Regimen

Study Evidence Comparator Efficacy
Hillmen et al. 2006 (TRIUMPH) Phase III Eculizumab Inferior stabilization of Hgb levels and QoL

No active treatment. Used as a comparator arm in one or more trials; for reference purposes, only.

References

  1. Hillmen P, Young NS, Schubert J, Brodsky RA, Socié G, Muus P, Röth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233-43. link to original article contains verified protocol PubMed
    1. Update: Hillmen P, Muus P, Dührsen U, Risitano AM, Schubert J, Luzzatto L, Schrezenmeier H, Szer J, Brodsky RA, Hill A, Socié G, Bessler M, Rollins SA, Bell L, Rother RP, Young NS. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007 Dec 1;110(12):4123-8. Epub 2007 Aug 16. link to original article PubMed