Waggoner, Thomas

Background Recurrent pericarditis may be mediated through inappropriate activation of the NACHT, leucine‐rich repeat, and pyrin domain‐containing protein 3 inflammasome. Pharmaceutically manufactured cannabidiol is an oral formulation that inhibits NACHT, leucine‐rich repeat, and pyrin domain‐containing protein 3 inflammasome activation and development of pericarditis in a preclinical model. Methods This Phase 2, open‐label, multicenter trial included adult patients with symptomatic recurrent pericarditis: pericarditis chest pain ≥4 on an 11‐point numerical rating scale with an elevated C‐reactive protein (≥1 mg/dL) or at least mild pericardial inflammation on cardiac magnetic resonance imaging. At enrollment, patients were on stable doses of non‐steroidal anti‐inflammatory drugs, colchicine, and/or corticosteroids. Cannabidiol was administered during an 8‐week treatment period and an optional 18‐week extension period when background therapy was tapered and discontinued. The primary efficacy end point was change in patient‐reported pericarditis pain. Secondary end points included normalization of C‐reactive protein and percentage of patients with recurrences. Results Among 27 patients (18 women, mean age 53 years), baseline maximal numerical rating scale pain score was 5.8±1.7, and 10 patients had elevated C‐reactive protein. At Week 8, maximal numerical rating scale pain score was 2.1±1.8, and median time to numerical rating scale score ≤2 was 5 days. Among the 10 patients with baseline C‐reactive protein elevation, C‐reactive protein was normal at Week 8 in 8 patients (80%). During the extension period, 17 (71%) of 24 patients remained free of pericarditis recurrence. A serious adverse event leading to cannabidiol discontinuation occurred in 1 patient. Conclusions In symptomatic patients with recurrent pericarditis, pharmaceutically manufactured cannabidiol appears safe and associated with reductions in pericarditis pain and systemic inflammation. Registration URL: clinicaltrials.gov ; Unique Identifier: NCT05494788.

Background: Recurrent pericarditis results from inflammasome activation and is associated with significant morbidity. Cannabidiol has been shown to block numerous inflammasome signaling pathways, including reducing transcription of pro-IL-1β and NLRP3, and inhibiting secretion of IL-1β and IL-6. Aim: To assess the impact of oral pharmaceutically manufactured (P-)cannabidiol in recurrent pericarditis patients (pts). Methods: Adult pts (≥18 years) with symptomatic, recurrent pericarditis (≥2 recurrences) were eligible for this open-label, multicenter study. Eligible pts had pericarditis chest pain with a numerical rating scale (NRS) pain score ≥4 within 7 days prior to enrollment, together with either elevated (≥1.0 mg/dL) C-reactive protein (CRP) within the prior 7 days or prior pericardial late gadolinium enhancement (LGE) on cardiac imaging. Pts had to be on chronic treatment with NSAIDs, colchicine or corticosteroids (any combination) with stable baseline (BL) doses. Oral P-cannabidiol was uptitrated to 10 mg/kg twice daily (BID), or maximum tolerated dose. The primary efficacy endpoint was improvement in NRS pain score at week 8 (WK8). A secondary efficacy endpoint among pts with elevated BL CRP was the percentage of pts with CRP normalization (≤0.5 mg/dL) at WK8. Results: 27 pts, mean age of 53 years (range 24-77), 18 of female sex, with a median of 3 prior pericarditis episodes were enrolled. CRP was ≥1.0 mg/dL in 10 pts (37%) at BL. Prior evidence of LGE was present in 21 pts (78%). At BL, 41% of pts were receiving corticosteroid therapy. The highest tolerated study medication dose was BID 10 mg/kg in 20 pts (74.1%), 7.5 mg/kg in 4 pts (14.8%), and 5 mg/kg in 3 pts (11.1%). All 27 pts (100%) completed the WK8 visit. Mean NRS score decreased by 3.7, from 5.8 at BL to 2.1 at WK8. In those with CRP elevation at BL, CRP normalized in 8 pts (80%) by WK8, with mean CRP decreasing from 5.71 to 0.31 mg/dL. Study medication was discontinued due to AEs in 2 pts (7.4%). 24 pts (89%) tolerated P-cannabidiol with a treatment response and proceeded into the 18-week extension period (EP) where background therapy is weaned. Conclusions: Among pts with symptomatic pericarditis recurrence, oral administration of P-cannabidiol led to a clinically relevant reduction in pericarditis chest pain (measured by NRS score) and in CRP. P-cannabidiol was shown to be safe and generally well tolerated, with the majority of pts reaching the target dose and continuing into the study EP.