[chantell.reagan]

Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare inherited auto-inflammatory conditions. CAPS are generally caused by mutations in the NLRP-3 gene which alters the protein cryopyrin. There are 3 syndromes that comprise CAPS: Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal-Onset Multisystem Inflammatory Disease (NOMID), which is the most severe form. Signs and symptoms include recurrent rash, fever/chills, joint pain, fatigue, and eye pain/redness. More severe forms can cause dramatic symptoms such as deafness, systemic amyloidosis and significant CNS disabilities. As plans move through the process of reviewing 2 new therapies recently approved for CAPS, there are several points to consider:

•What is the proportion of my population that might be affected by CAPS? The incidence in the US has been reported as 1 in 1M people.
•What therapy is used to treat CAPS? There is no cure for CAPS, and previous to newer therapies, symptoms were managed with NSAIDS, corticosteroids, thalidomide and TNF antagonists. Anakira, in several case studies and reports was shown to normalize amyloid A and C-reactive protein, while reducing symptoms when given daily; however, it is not indicated for CAPS. New to the market in 2009, Arcalyst (rilonacept) and Ilaris (canakinumab) are interleukin 1 (IL-1) blockers, which were FDA approved for CAPS, including FCAS and MWS (but not specifically NOMID).
•How do the IL-1 blockers compare to each other? Arcalyst acts on both IL-1alpha and beta subtypes, while Ilaris acts on the B-subtype only, but the clinical implication of this difference is unknown at this time. Arcalyst is approved for patients aged 12 years and over, while Ilaris is approved for patients >4 years. Additionally, Arcalyst is administered on a once-weekly basis (after a one-time loading dose of 320mg), while Ilaris needs only to be dosed once every 8 weeks. Neither drug is yet approved for use in treating NOMID, so currently both are restricted for use in the two other CAPS disorders. Both drugs are given SC, but due to reconstitution issues, they are recommended to be administered by a healthcare provider.
•What are clinical data differences between the IL-1 blockers? No head-to-head trials directly compared Arcalyst and Ilaris. Both drugs were studied for up to 48 weeks in placebo and open-label controlled trials. Both drugs demonstrated significant reductions in mean symptom scores and normalization of C-reactive protein and serum amyloid A levels.
•How long should treatment with an IL-1 blocker continue? These medications will likely need to be given as ongoing therapy to continue over the patient’s lifetime.
•What is the cost of treatment? According to publically available information (Medscape), the AWP of a single-dose vial (180 mg) of Ilaris is priced at $19,000, while that for a single-dose vial (220 mg) of Arcalyst is priced at $6000. These costs are equivalent to $114,000 in annual cost of therapy for Ilaris (average dose of 150 mg [1 vial] q 8 weeks) vs $288,000 for Arcalyst (average dose of 160mg [1 vial] q 4 weeks); a difference of $174,000 per year.
•What other agents are in the near-term pipeline for CAPS? There are no agents in the immediate late-stage pipeline for this indication; however, Arcalyst and Ilaris are being studied in areas such as refractory gout, systemic juvenile idiopathic arthritis, Type II diabetes and COPD.

Our analysis of six publicly available health plan policies revealed the following key findings:

•All plans require diagnosis of FCAS or MWS; however, 3/6 plans also require documentation of genetic mutation, typical symptoms, and functional impairment which limits activities of daily living (at least for 1 of the IL-1 inhibitors)
•2/6 plans apply different diagnostic criteria to Arcalyst vs Ilaris
•No policies explicitly permit coverage for NOMID at this time
•According to labeling 4/6 plans restrict age for use of Arcalyst but only 2/6 plans do so for Ilaris
•4/6 plans place quantity limits (at least for 1 of the IL-1 inhibitors)

The following figure provides a comparative summary of the selected policies (click on the image to enlarge it).



Given that Ilaris is approved for a wider patient population than Arcalyst, with a less frequent dosing schedule and significantly lower treatment costs, how will your plan position these IL-1 blockers?

Sources:

Arcalyst prescribing information (Regeneron)

Ilaris prescribing information (Novartis)

Church LD, Savic S and MF McDerrmott. Long term management of patients with cryopyrin-associated periodic syndromes (CAPS): focus on rilonacept (IL-1 Trap). Biologics. 2008 Dec;2(4):733-42.

National Institutes of Health. Clinical Trials

CAPS Community

Regeneron website:Arcalyst

Medscape monograph. Ilaris (canakinumab)

Medscape monograph. Arcalyst (rilonacept)

Aetna. Clinical Policy Bulletin: Arcalyst

Aetna. Clinical Policy Bulletin: Ilaris

BlueCross BlueShield of Alabama. Arcalayst policy

BlueCross Blue Shield of Alabama. Ilaris policy

Connecticare. Arcalyst policy

Connecticare. Ilaris policy

Humana. Medical policy

The Regence Group. Arcalyst policy

The Regence Group. Ilaris policy

Select Health. Arcalyst and Ilaris prior authorization form