Proven clinical efficacy in patients with iMCD

The efficacy of SYLVANT® (siltuximab) has been proven in the only randomized clinical trial conducted in patients with idiopathic multicentric Castleman disease (iMCD).1

(P = .0012)34%34% of patients receiving SYLVANT along with best supportive care (BSC) achieved the primary end point vs 0% of those onplacebo and BSC

All patients received BSC, which included management of effusions; use of antipyretic, antipruritic, antihistamine, and pain drugs; management of infections and transfusions; and standard management of infusion-related reactions, as specified in institutional guidelines.

The median progression-free survival (PFS) was 14.5 months (95% CI, 13.6-upper bound not reached) for patients on placebo, but was not reached for patients on SYLVANT.2

Baseline interleukin-6 levels were not associated with durable tumor and symptomatic response or best tumor response.1 This study was conducted before the diagnostic criteria for iMCD were established.1,3

Response to SYLVANT was significantly greater when minor criteria were met3,b

Diagnostic criteria for iMCD were established after the pivotal clinical trial. An additional efficacy analysis was performed by retrospectively applying the minor criteria to the siltuximab-treated patients from the pivotal clinical trial.1,3

(P = .0003)

Using Fisher’s exact test, those who met at least 2 minor criteria were significantly more likely to respond to SYLVANT than those who did not meet 2 minor criteria (P = .0003).3

bMinor Criteria include anemia, thrombocytopenia, constitutional symptoms, and ascites.3

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Response rate was greater in the subset of patients who met the current criteria for iMCD (≥2 minor criteria)3

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Patients who met 0 minor criteria (n=16) did not show response to SYLVANT and would not be eligible for siltuximab under current diagnostic guidelines3

Patients who were anemic showed a significant increase in hemoglobin1

Secondary end point analysis:

99101112131415Start of cycleWeeks on therapy

© Elsevier Inc. van Rhee et al. Lancet Oncol. 2014;15:966-974. Reprinted with permission.

%

of anemic patients (n=19/31)c achieved a >1.5 g/dL increase with SYLVANT (P = .0002)1

%

of anemic patients (n=13/31)c achieved normalized hemoglobin with SYLVANT1

cMean baseline hemoglobin level (g/dL) in all patients in the siltuximab arm was 11.8 (6.5-17.0).1

References: 1. van Rhee F, Wong RS, Munshi N, et al. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014;15(9):966-974. 2. van Rhee F, Rosenthal AL, Kanhai K, et al. Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease. Blood Adv. Published ahead of print July 6, 2022. doi:10.1182/bloodadvances.2022007112 3. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657.

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SYLVANT® (siltuximab) for injection

INDICATIONS AND USAGE

SYLVANT® (siltuximab) is an interleukin-6 (IL-6) antagonist indicated for the treatment of patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

Limitations of Use
SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL-6 in a nonclinical study.

IMPORTANT SAFETY INFORMATION

SYLVANT is contraindicated in patients experiencing a severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.

SYLVANT® (siltuximab) for injection

INDICATIONS AND USAGE

SYLVANT® (siltuximab) is an interleukin-6 (IL-6) antagonist indicated for the treatment of patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

Limitations of Use
SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL-6 in a nonclinical study.

IMPORTANT SAFETY INFORMATION

SYLVANT is contraindicated in patients experiencing a severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.

Concurrent Active Severe Infections: Do not administer SYLVANT to patients with severe infections until the infection resolves. SYLVANT may mask signs and symptoms of acute inflammation including suppression of fever and of acute Phase reactants such as C-reactive protein (CRP). Monitor patients receiving SYLVANT closely for infections. Institute prompt anti-infective therapy and do not administer further SYLVANT until the infection resolves.

Vaccinations: Do not administer live vaccines to patients receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens.

Infusion Related Reactions and Hypersensitivity: Stop the infusion of SYLVANT if the patient develops signs of anaphylaxis. Discontinue further therapy with SYLVANT.

Stop the infusion if the patient develops a mild to moderate infusion reaction. If the reaction resolves, the SYLVANT infusion may be restarted at a lower infusion rate. Consider medicating with antihistamines, acetaminophen, and corticosteroids. Discontinue SYLVANT if the patient does not tolerate the infusion following these interventions.

Administer SYLVANT in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation.

Gastrointestinal (GI) Perforation: Gastrointestinal (GI) perforation has been reported in clinical trials although not in MCD trials. Use with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with symptoms that may be associated or suggestive of GI perforation.

The most common adverse reactions (>10% compared to placebo) in the MCD clinical trial were rash, pruritus, upper respiratory tract infections, increased weight, and hyperuricemia.

Cytochrome P450 Substrates: Upon initiation or discontinuation of SYLVANT, in patients being treated with CYP450 substrates with a narrow therapeutic index, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) as needed and adjust dose. The effect of SYLVANT on CYP450 enzyme activity can persist for several weeks after stopping therapy. Exercise caution when SYLVANT is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable (e.g., oral contraceptives, lovastatin, atorvastatin).

Pregnancy and Lactation: SYLVANT may cause embryo-fetal harm when administered to pregnant women. Advise female patients of reproductive potential to use effective contraception during treatment with SYLVANT and for 3 months after the last dose. Advise females not to breastfeed during treatment with SYLVANT and for 3 months after the final dose.

Dosing and Administration: Perform hematology laboratory tests prior to each dose of SYLVANT therapy for the first 12 months and every 3 dosing cycles thereafter. If treatment criteria outlined in the Prescribing Information are not met, consider delaying treatment with SYLVANT. Do not reduce dose.

To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases, Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Before prescribing SYLVANT, please read the full Prescribing Information.

For your idiopathic multicentric Castleman disease (iMCD) Patients Taking SYLVANT® (siltuximab)

R.A.R.E.® can help

  • Co-pay assistance
  • Benefit investigations
  • Prior Authorization and Appeals Support:
    Phone: 1-855-299-8844
    Fax: 1-888-223-1746

One on one support

Helga will call enrolled patients to help:

  • Educate and answer questions about iMCD and SYLVANT
  • Help with access to SYLVANT medication
  • Connect them with other iMCD educational resources
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