Important Safety Information

  • WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

    Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.

    • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
    • Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection.
    • Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.

    Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone:1-888-SOLIRIS (1-888-765-4747) or at solirisrems.com.

How do I test for PNH?

Appropriate Testing for PNH

Testing for PNH is relatively inexpensive and requires only a peripheral blood sample. Such testing can improve the time to diagnosing PNH, which can otherwise be delayed from one to more than 10 years.1

The ICCS Guidelines

Review the full International Clinical Cytometry Society (ICCS) Guidelines for identifying and monitoring PNH-cell populations.

The Realities of Testing

The diverse and common symptomatology of PNH can delay diagnosis from 1 to more than 10 years1, therefore it is critical to test high-risk patient groups in an effort to make an earlier diagnosis of PNH.2

High-sensitivity* flow cytometry — performed on peripheral blood — is the gold standard diagnostic test for PNH.2,3,4

* Detects PNH cells down to a 0.01% clone size.


Overview of sample processing in flow cytometry3

  • Send peripheral blood samples to a lab that can perform high-sensitivity testing, in order to detect cell populations numbering as few as 0.01%

  • Stain cells with monoclonal antibodies against GPI-anchored proteins or markers for GPI anchor in both red blood cells (RBCs) and white blood cells (WBCs) that are specific for each cell lineage tested

    • Both RBCs and WBCs should be tested for the presence of PNH clones

    • Multiple markers should be used for each lineage tested, as recommended in the ICCS guidelines

  • Ensure appropriate numbers of gated cells are used for routine analysis and high-sensitivity flow cytometry

  • Report flow cytometric data by describing populations of both RBCs and WBCs that are abnormal or deficient in GPI anchors


Detection of populations of PNH-cell populations using flow cytometry

As an analytical tool, flow cytometry is performed using either monoclonal antibodies directed against GPI-anchored proteins (GPI-APs) or other markers that bind to GPI anchors present on the surface of RBCs and WBCs. Importantly, the proper sample considerations, cell gating strategies, and multiple lineage-specific antibody combinations are essential to support a result that is accurate and reproducible.5,6

Strategies for PNH testing5,6,7,8
Type of analysis Number of cells Target cell Gating strategies Informative reagents
High sensitivity (0.01%) 250,000 Red cells Glycophorin A + scatter CD59 ± CD55 in same or different colors
Granulocytes CD15/SSC FLAER *, CD24, CD66b, CD16† ; 2 reagents essential
CD55/CD59 combination not recommended
Monocytes‡
Routine (1%) 5000 Red cells Log FSC/SSC; glycophorin A optional CD59 ± CD55
Granulocytes CD45/SSC or CD15† (or equivalent)/SSC FLAER *, CD24, CD66b, CD16† ; 2 reagents essential
CD55/CD59 combination not recommended
Monocytes CD45/SSC or CD33/SSC or CD64/SSC or CD163/SSC FLAER *, CD14 ||, CD48 , CD55 , CD157

* The FLAER method is based on the ability of fluorescently labeled inactive variant of the bacterial protein aerolysin to bind selectively to GPI-APs.6

†† Polymorphic variants and loss of CD16 from eosinophils may limit usefulness; should never be used as sole reagent.

‡‡ Monocytes may not be suitable for high-sensitivity analysis because of the difficulty in collecting sufficient events, but if performed, lineage-specific gating using CD33 or CD64, and FLAER plus another reagent is essential.

|| CD14 is negative on dendritic cells and basophils that could be included in a monocyte gate, and is also dim or negative on immature monocytes, so should not be used as sole reagent; may be useful to combine with FLAER in dual parameter analysis, though FLAER may also be dim on normal basophils.

¶ Limited experience with these reagents.

Find a list of high-sensitivity flow cytometry laboratories in your area on our PNH Diagnostic Laboratory Services page.

blood

PNH Diagnostic Laboratory Services

A list of labs that perform high-sensitivity flow cytometry tests for PNH

Soliris Therapy

A patient brochure that provides information on PNH and treatment with Soliris.

brochure
return to top
 

Important Safety Information

CLOSE

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.

  • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection.
  • Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.

Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone:1-888-SOLIRIS (1-888-765-4747) or at solirisrems.com.

Indications and Usage

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Soliris is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

Atypical Hemolytic Uremic Syndrome (aHUS)

Soliris is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.

Limitation of Use

Soliris is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Contraindications

Soliris is contraindicated in:

  • Patients with unresolved serious Neisseria meningitidis infection

  • Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection

Warnings and precautions

Other Infections

Soliris blocks terminal complement activation; therefore patients may have increased susceptibility to infections, especially with encapsulated bacteria. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with Soliris may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenza type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenza type b (Hib) infections according to ACIP guidelines. Use caution when administering Soliris to patients with any systemic infection.

Monitoring Disease Manifestations After Soliris Discontinuation

Treatment Discontinuation for PNH

Monitor patients after discontinuing Soliris for at least 8 weeks to detect hemolysis.

Treatment Discontinuation for aHUS

After discontinuing Soliris, monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks. In aHUS clinical trials, 18 patients (5 in the prospective studies) discontinued Soliris treatment. TMA complications occurred following a missed dose in 5 patients, and Soliris was reinitiated in 4 of these 5 patients.

Clinical signs and symptoms of TMA include changes in mental status, seizures, angina, dyspnea, or thrombosis. In addition, the following changes in laboratory parameters may identify a TMA complication: occurrence of two, or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during Soliris treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during Soliris treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during Soliris treatment.

If TMA complications occur after Soliris discontinuation, consider reinstitution of Soliris treatment, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures.

Thrombosis Prevention and Management

The effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Therefore, treatment with Soliris should not alter anticoagulant management.

Infusion Reactions

As with all protein products, administration of Soliris may result in infusion reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no patients experienced an infusion reaction which required discontinuation of Soliris. Interrupt Soliris infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Adverse Reactions

The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) are: headache, nasopharyngitis, back pain, and nausea.

The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.

Please see full Prescribing Information for Soliris, including Boxed WARNING regarding serious meningococcal infection.