Company:

Regeneron

Interleukin-1 (IL-1) blocker.

Rilonacept 220mg; per vial; pwd for SC inj after reconstitution; preservative-free.

Cryopyrin-associated periodic syndromes (CAPS) including familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS).

Cryopyrin-associated periodic syndromes are rare genetic disorders that are characterized by symptoms such as fever, urticaria, arthralgia, myalgia, fatigue, and conjunctivitis. In most cases, the inflammatory system is disrupted by a mutation that results in an overproduction and release of activated interleukin-1 beta, which causes an exaggerated autoimmune response.

Rilonacept acts as a decoy receptor that binds interleukin-1 beta, preventing its interaction with cell surface receptors and disrupting inflammatory signaling. It is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human interleukin-1 receptor component and IL-1 receptor accessory protein linked to the Fc portion of human IgG1.

A randomized, double-blind, placebo-controlled study enrolling 47 patients was conducted to evaluate the safety and efficacy of rilonacept in treating CAPS. The two parts (A and B) of the study were conducted sequentially in the same patients with FCAS and MWS.

Part A was a double-blind 6-week phase while part B was a patient-blind 9-week phase. An optional open-label 24-week extension phase with rilonacept was conducted afterwards.

Patients rated symptoms on a scale of 1 to 10 in a daily questionnaire. The study evaluated the mean symptom score using the change from baseline to end of treatment. In most patients, improvement in symptom scores was noted within several days of starting treatment with rilonacept. In the first phase (part A), rilonacept was associated with more improvement in each of the five components of the composite endpoint (joint pain, rash, fever/chills, eye redness/pain, fatigue) than was placebo. Ninety-six percent of patients in the rilonacept group had at least a 30% improvement from the baseline in the composite score, compared to 29% of the placebo group; 87% of rilonacept-treated patients had at least a 50% improvement (8% for placebo); and 70% of rilonacept-treated patients had at least a 75% improvement (0% for placebo).

Part B was a randomized withdrawal period. Mean symptom scores in this phase increased more in patients withdrawn to placebo compared to those who stayed on rilonacept.

Treatment with rilonacept was associated with sustained reductions from baseline in mean levels of C-reactive protein and normalization of mean levels of serum amyloid A, both of which are indicators of inflammatory disease activity that are elevated in patients with CAPS.

Reductions in mean symptom scores, serum C-reactive protein, and serum amyloid A were maintained during the open-label phase for up to 1 year.

Give by SC inj into abdomen, thigh, or upper arm; rotate sites. ≥18yrs: Loading dose: 320mg on day 1 (split dose into 2x160mg at different sites), then 160mg as single dose once weekly.

Give by SC inj into abdomen, thigh, or upper arm; rotate sites. <12yrs: not recommended. 12–17yrs: Loading dose: 4.4mg/kg (max 320mg) in 1 or 2 inj (max 2mL/inj) on day 1; may split loading dose into 2 inj at different sites. Maintenance: 2.2mg/kg (max 160mg) once weekly.

Discontinue if serious infection develops. Do not start treatment with active or chronic infection. Before starting therapy: complete recommended immunization schedules (including pneumococcal and influenza), and evaluate and treat possible latent tuberculosis. Asthma. Diabetes. HIV, hep B, or hep C infection. Renal or hepatic impairment. Monitor lipid profile. Patients <18yrs: monitor growth and development. Pregnancy (Cat.C): not recommended (may cause fetal harm). Nursing mothers.

Avoid concurrent live vaccines. Infection risk with concomitant TNF blockers (eg etanercept, infliximab, adalimumab) or other IL-1 blockers (eg, anakinra): not recommended. Monitor drugs that affect or are affected by CYP450 (eg, warfarin). Caution with other immunosuppressants (eg, corticosteroids).

Inj site reactions, infections (eg, URI; may be serious/fatal); possible increased risk of malignancies, antibody formation, changes in lipid profile.

Single-dose vial—4

4/17/08