Eculizumab (Soliris) is a humanized monoclonal antibody that blocks the formation of terminal complement complex by preventing the enzymatic clevage of complement 5 (C5).

Uses:

• PNH, aHUS, MG, NMOSD

• DM, PM (infrequently)

AE:

• Nausea, back pain, nasopharyngitis, and headache.

• Renal insufficiency, anemia, leukopenia, dyspepsia, diarrhea, tachycardia, peripheral edema, fatigue, hypo and hypertension.

• Risk of meningococcal infection

Eculizumab (Soliris) for gMG. (REGAIN: Landmark Phase III Study in Refractory Generalized Myasthenia Gravis (gMG)

• Selected inclusion Crietria:

  • Male or female patients 18 years of age or more.

  • Positive serologic test for anti-AChR abs

  • Failed prior therapy over 1 or more years with

    • 2 or more ISTs, including steroids and/or other immunosuppressants OR

    • 1 or more IST and required chronic PLEX or IVIg

  • MG-ADL total score 6 or more at time of screening

  • On a stable dosage of immulnosuppressants or other concomitant medications.

  • MGFA Clinical Classification: Class II to IV (class I and V excluded)

  • Targeted therapy that is thought to reduce terminal complement activity (TCC C5b-9) depositing at the NMJ in adult patients with anti-AchR+ve gMG. Efficacy is well established.

• It is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Patients must enroll in this program. 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com

• Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Patients have to be immunized with meningococcal vaccination (MenACWY and MenB) at least 2 weeks prior to administering the 1st dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. Many also treat with antibiotics such as cephalosporin following vaccination. The 2nd doses of both vaccinations is given 8 weeks, following the 1st dose.

  • UNC experience: Treatment with eculizumab 2 weeks after the patient receives the first does of EACH vaccine. Antibiotics coverage is not used.

  • If the drug must be use emergently before the 2 week period then cephalexin is appropriate (1 g PO q12h). Literature will say to use cipro which of course is dangerous in MG patients.

• Vaccinations: Menactra (MenACWY ) and Bexsero (MenB) vaccines

• Dosing for adult patients with anti-AchR + gMG consists of a 4-week induction followed by the fifth dose 1 week later, then every 2 weeks thereafter:

  • 900 mg IV qweekly x 4 weeks, then 1200 mg on 5th week; then 1200 mg q2 weeks, thereafter.

  • 900 mg weekly for the first 4 weeks, followed by 1200 mg for the fifth dose 1 week later, then 1200 mg every 2 weeks thereafter

  • Consider port-placement if patient is amenable to the idea, as IV infusions may be need q2 weeks indefinitely.

  • 35 minutes IV infusions.

• Supplemental dose: 600 mg per each plasmapheresis or plasma exchange session to be given within 60 minutes (can be given later on same day) after each plasmapheresis or plasma exchange session.

  • One can do Eculizumab after PLEX (withing 60 minutes to hours later, but same day) but the patient will need booster doses each time they get PLEX. For example the maintenance dose is 1200 mg every 2 weeks. On can give the maintenance dose right after PLEX. Now if next week this patient needs PLEX, give a booster dose of 600 mg right after the PLEX. The 600 mg booster dose is to follow each PLEX session. Eculizumab has to immediately follow PLEX not days apart.

  • PLEX is very effective in removing eculizumab. The elimination half life for eculizumab is 270 to 370 hours. PLEX shortens it by >200 fold, down to about 1.5 hours. If possible, avoid doing both at the same time. Efficacy of eculizumab is usually evident within the first couple of weeks, typically by 6 weeks, and (by 12 weeks) based on REGAIN data.

  • If someone needs ongoing PLEX or IVIG as maintenance in addition to eculizumab, then the latter is not being effective.

  • If a patient who is doing well on eculizumab and develops a MG exacerbation, one could PLEX the patient as a single course for the exacerbation, then reload with eculizumab 900 mg IV qweekly x 4 weeks, then 1200 mg on 5th week; then 1200 mg q2 weeks, thereafter.

• Adverse effects: Musculoskeletal pain in >10% of patients. In >5% the following adverse effects were reported: GI (abdominal pain), peripheral edema, fever, HSV infections, contusion, headache, nasopharyngitis, diarrhea, arthralgia, URI, and nausea.

• While on eculizumab, patient should continue on immunsuppressants (prednisone, MMF, or AZA).

• Usually takes 2 -3 month to know if it is producing maximal effect. Patient typically improve during the induction infusion course.