Table 3.

Clinical studies that tested IL-1 blockers in acute and recurrent pericarditis.

Study	Study design	Treatment	Patients	Key results
Wohlford et al. [69]	Prospective open-label study	Anakinra 100 mg subcutaneously within 24 hours of hospital admission	6 patients with acute pericarditis with moderate-to-severe chest pain	Anakinra was administered a median of 20 h after hospital admission. Pain score decreased from a baseline of 6 (6–7.5) to 4 (2.5–4) after 6 h and to 2 (1.5–2.5) after 24 h (p = 0.012 and p = 0.002, respectively).
				IL-6 levels reduced within 24 h (95.3 [24.2–155.1] $\to$ 23.9 (4.5–71.9) pg/mL, p = 0.037) following anakinra administration.
				Pain reduction at 24 h was correlated with IL-6 reduction at 24 h (r = +0.966, p = 0.007).
				No AEs were described.
AIRTRIP study [7]	Double-blind, placebo-controlled, randomized withdrawal trial	Anakinra at 2 mg/kg daily (up to 100 mg) subcutaneously for 2 months.	21 patients (n = 11 anakinra, n = 10 placebo) with recurrent pericarditis ($\ge$3 recurrences), increased CRP, resistant to colchicine and dependent on glucocorticoid	In the open-label phase, all patients had a complete response to anakinra at day 8 as well as CRP normalized and pain rapidly reduced. All patients were able to stop glucocorticoids within 6 weeks.
		Patients who responded (i.e., resolution of pericarditis) were randomized to anakinra or placebo for 6 months or until pericarditis recurrence		During the double-blind treatment phase, pericarditis recurrence was experienced by 90% (n = 9/10) patients in the placebo group vs. 18.2% (n = 2/11) patients in the anakinra group (incidence rate, 0.11% of patients per year).
				Median time-to-flare was 72 (64–150) days after randomization in the placebo group, whereas it could not be computed in patients randomized to anakinra (p 0.001). Mean time-to-flare was 28.4 vs. 76.5 days in the placebo and anakinra groups, respectively (absolute mean difference of –48.1, 95% CI, –118.1 to 21.9 days).
				The most common AE in patients treated with anakinra was a local skin reaction at the injection site (95% patients).
IRAP study [70]	Multicenter observational cohort study	Anakinra 100 mg daily subcutaneously	224 patients with glucocorticoid-dependent and colchicine-resistant recurrent pericarditis	Recurrences occurred in 35% (n = 78/224) patients with a median flare-free of 10 months (5–18).
				After anakinra treatment, a median of zero recurrences occurred with an 83% reduction in recurrence rate (RR 0.17, 95% CI 0.14–0.20, p 0.001). After 36 months from anakinra initiation, 72% patients experienced none or at most one recurrence.
				A reduction of 91% for ED admissions (RR 0.09, 95% CI 0.06–0.13, p 0.001) and 86% for hospitalizations (RR 0.14, 95% CI 0.11–0.19, p 0.001) was observed in patients treated with anakinra.
				During follow-up, 8.9% were admitted to the hospital for pericardiectomy and discontinued anakinra.
				After anakinra treatment, glucocorticoids were tapered and NSAIDs suspended in most patients without recurrences (27% and 24% still on glucocorticoid and NSAID therapy, respectively; 58% on colchicine).
				Transient skin reaction at the injection site was the most frequent AE (38% of patients). Arthralgias and myalgias were found in 6% of patients, while 3% experienced infections during follow-up.
RHAPSODY study [9]	Phase 3 multicenter, double-blind, event-driven, randomized-withdrawal trial	Rilonacept as a loading dose of 320 mg (or 4.4 mg/kg in patients 18 years of age) subcutaneously, followed by weekly doses of 160 mg (or 2.2 mg/kg in patients 18 years of age) subcutaneously	86 patients in the 12-week run-in period.	Rilonacept greatly lowered risk of recurrences compared to placebo (HR 0.04, 95% CI 0.01–0.18, p 0.001). Median time to recurrence in the placebo group was 8.6 weeks, while it was not possible to compute this period in the rilonacept group because of too few events.
			61 patients who experienced clinical response during the run-in period (CRP $\le$0.5 mg/dL and no or minimal pain while on rilonacept monotherapy without recurrences) were randomized to continue rilonacept (n = 30) or placebo (n = 31)	Injection-site skin reactions and upper respiratory tract infections were the most common AEs.

Legend. AE, adverse event; AIRTRIP, Anakinra-Treatment of Recurrent Idiopathic Pericarditis; CI, confidence interval; CRP, C-reactive protein; ED, emergency department; HR, hazard ratio; IL-6, interleukin-6; IRAP, International Registry of Anakinra for Pericarditis; NSAID, non-steroidal anti-inflammatory drug; RHAPSODY, Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis, a pivotal Symptomatology and Outcomes stuDY; RR, rate ratio.