Rilonacept in Recurrent Pericarditis: Mechanism of Action, Patient Management, and Clinical Considerations

In an interview with Pharmacy Times®, Allan L. Klein, MD, FRCP (C), FACC, FAHA, FASE, FESC, director at Pericardial Disease Center and professor of medicine, and Sean Krohn, PharmD, CSP, MSCS, lead clinical pharmacist, specialty pharmacy, focused on rilonacept's mechanism of action in treating recurrent pericarditis. Specifically, the experts discussed how rilonacept blocks IL-1 inflammatory pathways by trapping IL-1 alpha and beta and interrupting the inflammatory cascade. Klein and Krohn outlined the treatment progression for pericarditis, highlighting a paradigm shift towards using biologics like rilonacept earlier in the treatment process, especially for patients struggling with traditional therapies like steroids. The conversation detailed the specific inflammatory process triggered by complications like atrial fibrillation ablation, explaining how macrophages and inflammasomes contribute to pericardial inflammation. Additionally, the experts covered critical aspects of rilonacept administration, emphasizing the importance of proper storage, patient education, injection training, and ongoing clinical support.

Pharmacy Times: Rilonacept's mechanism of action as an IL-1 inhibitor is key to its efficacy in recurrent pericarditis. Could you elaborate on the specific inflammatory pathways involved in pericarditis that rilonacept targets and how this differs from traditional anti-inflammatory treatments?

Allan L. Klein, MD, FRCP (C), FACC, FAHA, FASE, FESC: The question is about the rilonacept mechanism of action, so I'll take you through a scenario. Somebody has an atrial fibrillation ablation, and they have a complication; they perforate, and there's blood that gets into the pericardial space. What happens is blood in the pericardial space is a bad thing. Macrophages get attracted to the surface; IL-alpha is released as macrophages are attracted. The IL-alpha attaches to the macrophage, and inside the cell there's what you call an inflammasome. The inflammasome is a cellular mechanism that gets activated, and the IL-beta goes from pro-form to an active form. The IL-alpha and beta attach to the capillaries, causing capillary leak. Then you get a white blood cell coming to the scene. You get capillary leak, and you get a whole cascade of inflammation. The IL-1 blockers, in particular, rilonacept traps IL-alpha and beta, and ankyrins is basically a blocker of IL-alpha and beta as well. That's the mechanism, so if you had an IL blocker that targets this type of mechanism, you would have a good thing for recurrence and block the whole cycle.

Pharmacy Times: What are the typical patient profiles for whom you consider rilonacept therapy, particularly in the context of recurrent pericarditis episodes or those refractory to conventional treatments? Are there specific comorbidities or patient characteristics that influence your decision?

Klein: In terms of the management of pericarditis and recurrent pericarditis, let me just go through definitions. Acute pericarditis is the inflammation of the lining of the heart. Usually, it occurs for 4 to 6 weeks; recurrent pericarditis means that as you're on the medicine and you start to taper, it comes back and recurs after 4 to 6 weeks, and usually less than 3 months. Most patients will go on standard therapy, level 1 therapy, including NSAIDs, usually ibuprofen, and exercise restriction in previous years. The next level would be low-dose steroids, half a milligram per kilogram of prednisone. Then the third line would be the IL-1 blockers or methotrexate. The fourth line would be the pericardiectomy. Currently there's a paradigm shift, so you basically go from level 1, and you bypass steroids and go to the biologics. Typically, in our trials, the Rhapsody trial is really patients that we're stuck on steroids, NSAIDs, or corticosteroid-resistant and steroid-dependent, and that's where the rilonacept worked, but based on that data and some current data, we try to bypass level 2 with the steroids and go right to the biologics. The classic comorbidities are that you're failing your standard of care, and you're still flaring out. Imagine a young person, let's say in their 30s, that has recurrent pericarditis, and you're not tolerating or can't take colchicine and try to put them on steroids; you're going to put on a lot of weight. You would have trouble weaning off the steroids over many months, so that's why biologics may be a better thing to go with.

Pharmacy Times: From your perspective, what are the most critical aspects of rilonacept administration that pharmacists should be aware of to ensure patient safety and adherence (i.e., injection technique, storage requirements)?

Sean Krohn, PharmD, CSP, MSCS: I would say the most critical aspects would be storage of the medication, as well as the importance of injection training by a health care professional prior to patients starting the injection on their own. Rilonacept is refrigerated, but we also go a little bit further with our education with our patients. Let them know that the medication, for example, will be shipped with ice packs in a cooler. With that said, we never automatically shipped the medication to the patient's home without them being aware. Our certified pharmacy technicians contact the patient prior to them running out of meds to confirm that they A, need the medication, and B, confirm a specific delivery date that works for them. A gold standard for specialty pharmacies is 24/7 access to a pharmacist for clinical and non-clinical inquiries. If patients have a storage stability question over the weekend, for example, they can speak with a clinical pharmacist here that very day, versus having to wait a little too late the following work week, for example. Rilonacept is reconstituted, so we wouldn't expect patients to begin injecting on their own without health care professional training, whether this be virtual or in person. Injection training is very important, especially with this medication, as the patient must learn the reconstitution process and subcutaneous injection technique, as well as monitor for any potential injection-related reactions that do rarely occur with the med.