RARE DISEASE
Idiopathic recurrent pericarditis
Idiopathic recurrent pericarditis
Idiopathic recurrent pericarditis
Synonyms: Idiopathic relapsing pericarditis
Synonyms: Idiopathic relapsing pericarditis
Synonyms: Idiopathic relapsing pericarditis
Drug discovery
9
drugs
With orphan designations
Overview
Idiopathic Recurrent Pericarditis (IRP) is an autoinflammatory disorder characterized by recurrent pericardial inflammation, often without identifiable triggers. It manifests with chest pain, pericardial effusions, and elevated inflammatory markers, driven by dysregulated interleukin-1 (IL-1) signaling. First-line therapy combines NSAIDs/aspirin with colchicine to reduce recurrence risk. Refractory cases may require IL-1 inhibitors (e.g., anakinra, rilonacept), which demonstrate efficacy in corticosteroid-dependent patients. Chronic inflammation and prolonged corticosteroid use contribute to morbidity, including chronic pain and reduced quality of life [1][3][6][12][16].
Burden
Median disease duration: 2.8 years; 15–42% develop multiple recurrences [2][4].
Hospitalization costs 2.8× higher vs non-recurrent cases; $2,728/month healthcare costs for refractory patients [4][7].
Corticosteroid dependence linked to chronic pain, osteoporosis, and impaired quality of life [12][16].
Categories: rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood
Research Papers
296 drug discovery papers about Idiopathic recurrent pericarditis, with 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
296 drug discovery papers about Idiopathic recurrent pericarditis, with 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-09 | Prednisone in the Management of Pericarditis A Systematic Review.
Corticosteroids are widely used in pericarditis despite guideline recommendations reserving them for select indications. Observational studies have reported inconsistent associations between corticosteroid use and pericarditis recurrence, and optimal dosing and tapering strategies remain unclear. We conducted a systematic review of oral corticosteroids for acute or recurrent pericarditis to characterize patterns of treatment and evaluate the association between corticosteroids and pericarditis recurrence across different disease contexts. MEDLINE, EMBASE, CENTRAL, and Scopus were searched from inception to November 26, 2025. Studies enrolling adults with acute or recurrent pericarditis treated with oral corticosteroids were included. Randomized trials, cohort studies, and case-control studies reporting clinical outcomes were eligible. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Data were synthesized descriptively due to anticipated clinical and methodological heterogeneity. Ten studies (2 prospective, 8 retrospective) including 2632 patients (800 corticosteroid-treated) met inclusion criteria. Prednisone was most frequently studied, with heterogeneous dosing (0.25-1.0 mg/kg/day) and non-standardized tapering strategies. Follow-up ranged from 1 to 6.7 years, and overall risk of bias was moderate with limited adjustment for confounding. Findings on recurrence were inconsistent in acute idiopathic and post-procedure pericarditis, while most studies in recurrent pericarditis reported higher recurrence with corticosteroid exposure. Evidence evaluating oral corticosteroids in pericarditis is limited by heterogeneity, confounding, and inconsistent reporting of treatment strategies. Observational data show variable associations with recurrence across clinical contexts. High-quality randomized trials stratified by pericarditis etiology and acuity are needed to define the optimal use of corticosteroids in pericarditis.
2026-07-15 | The paradigm shift in corticosteroid therapy for idiopathic pericarditis: from high-dose regimens to precision therapy.
Idiopathic and recurrent pericarditis are increasingly recognised as autoinflammatory conditions driven by the NLRP3 inflammasome and interleukin-1 signalling. Despite this shift in understanding, the misuse of high-dose corticosteroids has often led to a 'massacre of the innocents', transforming acute events into chronic, steroid-dependent diseases. This narrative review analyses the evolution of corticosteroid use in pericarditis, emphasising the transition from aggressive loading doses to the low-dose, 'rheumatological' strategies codified in the 2025 European Society of Cardiology (ESC) guidelines.Evidence confirms that medium-dose prednisone (0.2-0.5 mg/kg/day), when integrated into triple therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, reduces recurrence rates and iatrogenic toxicity compared to traditional high-dose regimens (1.0 mg/kg/day). A critical challenge remains the tapering process; rapid withdrawal triggers inflammatory rebounds, necessitating meticulous, long-lasting (months-years), C-reactive protein (CRP)-guided reductions as small as 5 to 1.25 mg every two to six weeks, similar to the tapering used in polymyalgia rheumatica. Chronic maintenance with low-dose prednisone (≤5 mg/day) may be considered in selected cases, with a good risk-benefit balance. The elderly usually require medium dosages (e.g. prednisone 12.5-25 mg), pregnant women no more than 10 mg, while children should avoid chronic corticosteroid therapy. CRP-negative cases may benefit from low doses (5 mg). Given the long-term duration of therapy, bone protection therapy is essential yet underutilised, while protonpump inhibitors should be used only for concomitant NSAIDs therapy. Corticosteroids are generally ineffective in chronic idiopathic pericardial effusions with normal CRP.In conclusion, modern management redefines corticosteroids as a precision tool rather than a blunt anti-inflammatory agent.
2026-05-27 | Expanding the Therapeutic Landscape of Pericarditis: A Systematic Review of the Use of Conventional Immunosuppressants.
Background and Objectives: While interleukin-1 inhibitors represent the standard of care for refractory idiopathic recurrent acute pericarditis, current guidelines also endorse conventional immunosuppressive (IS) agents as potential alternatives. The use of conventional IS agents is particularly relevant in specific clinical scenarios, such as systemic immune-mediated disease (SID)-associated pericarditis. However, existing evidence regarding their efficacy and safety for pericarditis treatment remains fragmented, deriving exclusively from case reports, case series, and small monocentric observational studies. Our aims are: To characterize the clinical and diagnostic profiles of patients with pericarditis treated with conventional IS agents and to evaluate the therapeutic efficacy and safety of such agents. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines. Major electronic databases were searched from January 1970 to March 2026 for case reports, case series, and observational studies detailing the use of conventional IS therapies for pericarditis. Clinical and therapeutic data, including specific IS indications and dosing regimens, were systematically extracted. Results: The final analysis included 39 reports comprising 75 patients (60% female; median age 36.0 years). The underlying pericarditis aetiology was predominantly SID-related (53%, n = 40) or idiopathic/presumed viral recurrent disease (40%, n = 30). The most frequently prescribed first-line IS agents were azathioprine (44%) and methotrexate (25%). Across published reports, IS therapy was described as achieving pericarditis clinical resolution in all cases and facilitated corticosteroid withdrawal in 72% of patients. Overall, pericarditis recurrence while on IS therapy occurred in only 10% of the cohort. Adverse events requiring IS withdrawal were rare (n = 2, 3%). Conclusions: Conventional IS agents appear effective and generally well tolerated in the published literature on SID-associated and isolated recurrent pericarditis. These findings reinforce the clinical utility of conventional IS therapies as a viable, steroid-sparing strategy when targeted biologic therapies lack sufficient investigation.
2026-05-26 | Recurrent Pericarditis in a Middle-Aged Female with MEFV Mutation.
Recurrent pericarditis (RP) remains challenging, especially in tuberculosis (TB)-endemic regions where empirical anti-TB therapy is often unnecessarily prolonged. We report a 35-year-old woman with three RP episodes over six months, presenting with pleuritic chest pain, elevated inflammatory markers, and moderate-to-large pericardial effusion. Extensive infectious (including TB), autoimmune, and malignancy workups were negative. Cardiac magnetic resonance revealed persistent pericardial late gadolinium enhancement despite clinical remission. Whole-exome sequencing identified a heterozygous MEFV c.442G>C (p.Glu148Gln) variant, suggesting an autoinflammatory predisposition. Although the patient finally achieved sustained symptom-free status for six months on a standardized low-dose colchicine regimen, still over 10% of patients have recurrent symptoms receiving colchicine in addition to conventional anti-inflammatory therapy with aspirin or ibuprofen. This case highlights the shifting paradigm from an infection-centered to an autoinflammatory framework for RP in TB-endemic countries, underscores the role of MEFV variants in idiopathic recurrent pericarditis, and illustrates the real-world gap between genetic insights and therapeutic accessibility to IL-1 inhibitors in resource-limited settings.
2026-03-14 | PERICARDITIS AS A POTENTIAL MARKER OF OCCULT CANCER - A COMPREHENSIVE REVIEW OF EPIDEMIOLOGY, PATHOPHYSIOLOGY AND CLINICAL IMPLICATIONS
Pericarditis, traditionally considered a benign and self-limiting condition, is increasingly recognized as a potential marker of occult malignancy. Epidemiological evidence indicates a significantly increased risk of cancer—particularly lung, hematologic, breast, and gastrointestinal malignancies—within the first year after diagnosis. The association is stronger in elderly patients and in cases of recurrent, idiopathic, or hemorrhagic pericardial effusion. Proposed mechanisms include direct tumor invasion of the pericardium, lymphatic or hematogenous metastasis, and paraneoplastic inflammatory processes. In some patients, pericarditis precedes the diagnosis of cancer by several months, functioning as an early clinical warning sign. When common infectious or autoimmune causes are excluded, further evaluation with advanced imaging, pericardial fluid cytology, and tumor marker analysis is recommended. Maintaining a high index of suspicion in high-risk individuals may enable earlier cancer detection. A structured diagnostic approach and timely oncologic referral are essential to improve clinical outcomes and ensure appropriate management.
antibodies
2026-09-30 | Emerging therapies for pericarditis: from anti-IL-1 agents to novel therapeutic options.
Although often self-limited, acute pericarditis recurs in up to 30% of patients. Recurrent pericarditis (RP) causes substantial morbidity (pain, fatigue, and impaired quality of life) and can lead to constriction. Traditional treatments have important limitations, including corticosteroid dependence, recurrent flares, and treatment-related adverse effects. Emerging targeted immunomodulators are therefore under active investigation. This review summarizes the burden of pericarditis across etiologies, current therapies, and the global market for pericarditis treatment. We then focus on novel agents in development with an emphasis on phase II/III studies. The pathobiology of pericardial inflammation (notably interleukin (IL)-1 and inflammasome pathways) is discussed as the rationale for targeted drugs. We review key trials of IL-1 inhibitors, NLRP3 inhibitors (VTX2735), and other innovations (e.g. cannabidiol-based CardiolRx). Potential obstacles to development are examined. Randomized-withdrawal trials support a marked reduction in recurrences with IL-1 blockade in selected patients with inflammatory, colchicine-resistant and corticosteroid-dependent RP. However, open-label enrichment, small samples, short follow-up, uncertain durability after withdrawal, cost, and limited evidence outside idiopathic or post-cardiac injury disease restrict generalizability. New pipeline agents hold promise for broader use, however remain investigational until controlled trials establish their efficacy and long-term safety.
2026-06-30 | Current issues in the treatment of pericarditis: practical guidelines and pharmacotherapy
The article presents a clinical and pharmacological review of modern approaches to the diagnosis and treatment of pericarditis, with an emphasis on practical recommendations for selecting anti‑inflammatory therapy. The etiological structure of pericardial diseases and the key clinical manifestations of acute, recurrent, and chronic pericarditis are examined. The regimens for using non‑steroidal anti‑inflammatory drugs, colchicine, and glucocorticosteroids are analyzed in detail, along with a comparative assessment of their efficacy and safety. Special attention is paid to the use of interleukin‑1 inhibitors in patients with idiopathic recurrent pericarditis: the results of the COURSE study, dosing regimens for golimumab, and recommendations from experts of the Russian Society of Cardiology are presented. Issues related to the safety of combination therapy with NSAIDs and oral anticoagulants are considered separately. Algorithms for selecting therapy are proposed, depending on the severity of the disease, the response to standard regimens, and the patient’s comorbid background.
2026-05-01 | Case Report: Safety and efficacy of combination therapy with adalimumab and anakinra in two patients with severe inflammatory diseases.
Chronic inflammatory diseases in children can involve distinct immunologic pathways, occasionally necessitating dual biologic therapy when single-agent treatment is insufficient. Evidence on combined IL-1 and TNF-α inhibition remains limited. A 15-year-old girl with ulcerative colitis and recurrent pericarditis received adalimumab and anakinra, achieving clinical remission without infections over eight months. An 11-year-old boy with juvenile idiopathic arthritis, uveitis, and colchicine-resistant familial Mediterranean fever received combined adalimumab and anakinra, achieving low disease activity in both conditions at six months, without adverse events. Dual blockade of TNF-α and IL-1 may be rational in selected patients due to overlapping and complementary roles of these cytokines in driving inflammation. Our cases illustrate that this combination can be effective and well tolerated with careful monitoring. In carefully selected pediatric patients, simultaneous TNF-α and IL-1 inhibition may provide clinical benefit. Further studies are required to assess long-term safety and efficacy.
2025-11-10 | Tolicizumab: a new option for refractory idiopathic recurrent pericarditis: a case report.
Recurrent pericarditis is the most common and troublesome complication of pericarditis and can be particularly challenging when it becomes refractory to conventional therapies, often resulting in a prolonged disease course. Interleukin-1 (IL-1) inhibitors have transformed the management of such cases; however, not all patients tolerate or respond adequately to these agents. We present a 37-year-old man suffering from idiopathic recurrent pericarditis since the age of 25. After failure of standard therapies, he became corticosteroid-dependent, so treatment with anakinra (an IL-1 inhibitor) was attempted twice, but discontinued early due to allergic reactions. As the recurrences were always characterised by an overt inflammatory phenotype (characterised by fever, increased C-reactive protein, and pericardial effusion), we administered off-label tocilizumab (an IL-6 receptor antagonist) as a last treatment option. The patient gained rapid benefit and was able to discontinue steroid therapy during the 6-month follow-up, achieving complete recovery from pericarditis. Interleukin-6 is a key cytokine in the pathogenesis of pericarditis, acting synergistically with IL-1 to drive inflammation and acute phase responses. In our patient, blockade of IL-6 with tocilizumab led to the complete resolution of inflammation, suggesting a possible new therapeutic option for refractory cases. This result highlights the potential of IL-6 inhibition as an alternative strategy, when IL-1 blockers are contraindicated or ineffective.
2025-05-27 | Dual Immunotherapy for Pericardial Mesothelioma That Developed After a Decade-Long Idiopathic Pericarditis: A Case Report.
Malignant pericardial mesothelioma (MPeM) is exceptionally rare, and its association with long-standing idiopathic pericarditis remains unreported. We present a 46-year-old woman with a decade-long history of recurrent idiopathic pericarditis who developed multiple pericardial nodules, mediastinal lymphadenopathy, and metastatic liver and bone lesions. A core needle biopsy confirmed biphasic MPeM. Due to her pericardial condition, she initially received platinum-based chemotherapy instead of immunotherapy, but the disease progressed. She then underwent dual immune checkpoint inhibition (ICI) and achieved a significant clinical and radiological response. This case raises the possibility of chronic inflammation contributing to pericardial malignancy and underscores the potential role of dual ICI in this rare and challenging disease.
proteins
2026-08-14 | Case Report: From idiopathic recurrent pericarditis to systemic Behçet’s Disease: unmasking a unified IL-1-driven autoinflammatory phenotype
Background Recurrent idiopathic recurrent pericarditis (RP) is increasingly recognized as an organ-specific autoinflammatory syndrome driven by the interleukin-1 (IL-1) axis. Behçet’s Disease (BD), a systemic vasculitis, exhibits significant pathogenetic overlap with RP through IL-1 mediated hyperinflammation, particularly in phenotypes dominated by serositis. The clinical evolution of prolonged, seemingly idiopathic RP into overt, systemic BD upon the tapering of targeted therapy remains a critical, yet underreported, observation. Case presentation A 42 years old female with corticosteroid-dependent, colchicine-resistant RP achieved complete and sustained clinical and biochemical remission using the IL-1 receptor antagonist, Anakinra, for almost 30 months, despite the tapering started after 18 months of continuous therapy with Anakinra, associated to colchicine and a quick tapering and withdrawal of corticosteroids. Following the elective tapering of Anakinra, the patient remained stable for three months with a dose of an injection of 100mg of Anakinra three times per week, before suffering a severe pericardial relapse concurrent with the systemic onset of systemic BD. The clinical condition observed fulfilled the International Criteria for Behçet’s Disease (ICBD), featuring recurrent oral and genital ulcerations, erythema nodosum and a positive pathergy test. The immediate reinitiation of Anakinra (100mg daily) led to the rapid and complete resolution of both the pericardial inflammation and all systemic mucocutaneous manifestations. Conclusions This case highlights a potential pathogenetic overlap between refractory RP and serositis-dominant BD phenotypes, suggesting that isolated RP may, in select cases, represent an early mono-organ precursor of a systemic autoinflammatory propensity. Furthermore, it provides clinical rationale for considering IL-1 blockade in serositis-dominant BD, though larger prospective studies are needed to confirm these findings.
2026-08-01 | Recurrent pericarditis in children: evidence, controversies, and emerging perspectives.
Recurrent pericarditis complicates approximately one-third of initial pericarditis episodes in children. Once considered a postinfectious sequel, it is now understood as an autoinflammatory disorder sustained by dysregulated interleukin-1 signaling and inflammasome hyperactivation. This review evaluates therapeutic strategies for idiopathic recurrent pericarditis in patients younger than 18 years using the PICO framework. First-line management with nonsteroidal anti-inflammatory drugs and colchicine remains the therapeutic backbone, with colchicine conferring a roughly 50% reduction in relapse risk. Glucocorticoids, although acutely effective, predispose to steroid-dependence and rebound flares, and should be reserved for refractory disease at low doses. IL-1 receptor antagonism, principally anakinra, has emerged as a transformative steroid-sparing option for colchicine-resistant or steroid-dependent cases, achieving rapid symptom control and durable remission in most treated children. Nonetheless, pediatric evidence remains limited to retrospective cohorts and small case series, highlighting the need for prospective controlled trials, standardized outcome definitions, and long-term safety surveillance of biologic agents.
2026-05-16 | Idiopathic recurrent pericarditis in children: a tertiary care cohort highlighting the emergence and effectiveness of interleukin-1 blockade.
Idiopathic recurrent pericarditis (IRP) is an increasingly recognized inflammatory condition in children, characterized by recurrent flares and therapeutic challenges, with emerging evidence supporting a role for interleukin-1 (IL-1)-mediated pathways. This study aimed to characterize the clinical features of a pediatric IRP cohort at our center, to examine clinically relevant differences between patients requiring and not requiring anakinra, and to evaluate anakinra effectiveness by assessing changes in disease activity before and after treatment. In this single-center retrospective cohort study, 26 children with IRP were evaluated in terms of demographic, clinical, laboratory, genetic, and treatment characteristics. Patients were stratified according to anakinra requirement, and these characteristics were compared between groups. In patients receiving anakinra, treatment effectiveness was assessed by comparing disease activity before and after therapy using annualized attack rate (AAR) and inflammatory markers. The cohort showed a male predominance (19/26, 73%), with a median age at diagnosis of 114 months (IQR, 48-168). Chest pain was the most common presenting symptom (16/26, 62%). Pericardial effusion was present in all patients (26/26, 100%), while pleural effusion was observed in 12/26 (46%). Despite conventional therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids, steroid dependency developed in 9/22 patients (41%). Anakinra was required in 16 patients (62%) and was associated with a marked reduction in disease activity, with a median relative decrease in AAR of 89.4% (IQR, 56.7-100%); a ≥ 50% reduction in AAR was achieved in 12/16 patients (75%). Significant and concordant reductions in inflammatory markers were observed. Relapse frequently occurred during anakinra dose spacing or discontinuation, while corticosteroid withdrawal was achieved in most treated patients. Patients requiring anakinra had higher baseline disease activity. Idiopathic recurrent pericarditis in children represents a heterogeneous and frequently relapsing inflammatory condition in which conventional therapies often fail to achieve sustained disease control. As an IL-1 blockade, anakinra emerges as a key therapeutic option, enabling corticosteroid sparing while effectively achieving disease control through targeting underlying innate immunity pathways. • Idiopathic recurrent pericarditis (IRP) in children is characterized by recurrent inflammatory flares and frequent treatment resistance, with conventional therapies (NSAIDs, colchicine, and corticosteroids) often being insufficient and associated with steroid dependency. • Increasing evidence implicates autoinflammatory pathways in disease pathogenesis, highlighting the potential role of IL-1 inhibition in refractory cases. • The high prevalence of MEFV-associated variants, frequent steroid dependency, and substantial use of IL-1 inhibitors collectively support an auto inflammatory-driven disease model in pediatric IRP. • Anakinra markedly reduces disease activity even in patients with high baseline inflammatory burden; however, sustained disease control requires continuous therapy, as dose spacing is associated with increased relapse rates.
2026-02-28 | Refractory recurrent pericarditis associated with MEFV E148Q variant: selective response to IL-1 receptor antagonism
Interleukin (IL)-1–mediated autoinflammation is increasingly recognised as a driver of recurrent idiopathic pericarditis, particularly in patients with systemic inflammation, glucocorticoid dependence, and suboptimal response to standard therapy, including nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine. Recent studies have shown that low-penetrance variants in autoinflammatory genes such as the Mediterranean fever gene (MEFV) may amplify inflammasome activation, which may underlie treatment resistance in some patients.
2025-11-01 | Rilonacept as monotherapy for long-term recurrent pericarditis management: sustained disease control over three years
Abstract Background Recurrent pericarditis (RP) predominantly shows features consistent with IL-1-mediated chronic autoinflammatory disease (1-4). A recent analysis suggested that supplementing anakinra with colchicine incrementally reduced pericarditis recurrence vs. anakinra alone (5). Rilonacept (a weekly IL-1α and IL-1β cytokine trap with 6-week washout) prevents engagement with IL-1 receptor, inhibiting both IL-1α and IL-1β activity (6). The Phase 3 trial RHAPSODY demonstrated rilonacept efficacy in two independent analyses: Randomized Withdrawal (RW) and Long-Term Extension (LTE) periods (7,8). Purpose Assess long-term recurrence-free persistence with rilonacept as monotherapy in pts with RP during the combined RW and LTE periods of RHAPSODY. Methods Post-hoc analysis. Freedom from recurrence on rilonacept monotherapy was quantified using the Kaplan-Meier (KM) method from RW start (if randomized to rilonacept) or from initiation of bailout rilonacept (if randomized to placebo) until the end of treatment. Prespecified recurrence adjudication criteria were pericarditis pain (numerical rating scale [NRS]) ≥4 plus C-reactive protein (CRP) ≥1 mg/dL. Per RHAPSODY protocol, background therapies were discontinued during the Run-In Period before randomization. In pts treated with rilonacept, concomitant colchicine was not added during the RW period. In the LTE, 6.8% (5/74) of pts added colchicine: one for 2 days of chest pain without CRP elevation, 4 in the absence of chest pain, CRP elevation, or recurrence; these 5 pts were censored in the KM curve at 6 days after last rilonacept dose or at colchicine initiation (whichever was first). One additional pt added colchicine prophylactically before an intentional rilonacept treatment interruption for elective cardiac surgery and experienced a recurrence after this interruption; this pt was not censored from the recurrence-free persistence analysis at colchicine initiation in order to capture this event. Results 74 pts (mean [SD] age 43.9 [15.7] years, 83.8% idiopathic pericarditis, mean [SD] disease duration 2.5 [3.2] years) were analyzed over three years. Rilonacept was well tolerated. Recurrence-free persistence was 95.9% (n=71/74) while receiving rilonacept as monotherapy (Figure 1). The three observed adjudicated recurrences were each associated with temporary interruptions of 1-3 doses of rilonacept. Conclusions Rilonacept as monotherapy provided recurrence-free persistence over the three-year trial duration when used continuously without interruption; pericarditis recurrences occurred only after interruptions. These findings support evidence-based use of rilonacept as monotherapy, minimizing the need for adjunctive treatments and reducing polypharmacy in long-term RP management. Further investigations are warranted to address how to assess pts as candidates for long-term treatment with rilonacept and when to cease rilonacept treatment.
small molecules
2026-08-09 | Prednisone in the Management of Pericarditis A Systematic Review.
Corticosteroids are widely used in pericarditis despite guideline recommendations reserving them for select indications. Observational studies have reported inconsistent associations between corticosteroid use and pericarditis recurrence, and optimal dosing and tapering strategies remain unclear. We conducted a systematic review of oral corticosteroids for acute or recurrent pericarditis to characterize patterns of treatment and evaluate the association between corticosteroids and pericarditis recurrence across different disease contexts. MEDLINE, EMBASE, CENTRAL, and Scopus were searched from inception to November 26, 2025. Studies enrolling adults with acute or recurrent pericarditis treated with oral corticosteroids were included. Randomized trials, cohort studies, and case-control studies reporting clinical outcomes were eligible. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Data were synthesized descriptively due to anticipated clinical and methodological heterogeneity. Ten studies (2 prospective, 8 retrospective) including 2632 patients (800 corticosteroid-treated) met inclusion criteria. Prednisone was most frequently studied, with heterogeneous dosing (0.25-1.0 mg/kg/day) and non-standardized tapering strategies. Follow-up ranged from 1 to 6.7 years, and overall risk of bias was moderate with limited adjustment for confounding. Findings on recurrence were inconsistent in acute idiopathic and post-procedure pericarditis, while most studies in recurrent pericarditis reported higher recurrence with corticosteroid exposure. Evidence evaluating oral corticosteroids in pericarditis is limited by heterogeneity, confounding, and inconsistent reporting of treatment strategies. Observational data show variable associations with recurrence across clinical contexts. High-quality randomized trials stratified by pericarditis etiology and acuity are needed to define the optimal use of corticosteroids in pericarditis.
2026-07-15 | The paradigm shift in corticosteroid therapy for idiopathic pericarditis: from high-dose regimens to precision therapy.
Idiopathic and recurrent pericarditis are increasingly recognised as autoinflammatory conditions driven by the NLRP3 inflammasome and interleukin-1 signalling. Despite this shift in understanding, the misuse of high-dose corticosteroids has often led to a 'massacre of the innocents', transforming acute events into chronic, steroid-dependent diseases. This narrative review analyses the evolution of corticosteroid use in pericarditis, emphasising the transition from aggressive loading doses to the low-dose, 'rheumatological' strategies codified in the 2025 European Society of Cardiology (ESC) guidelines.Evidence confirms that medium-dose prednisone (0.2-0.5 mg/kg/day), when integrated into triple therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, reduces recurrence rates and iatrogenic toxicity compared to traditional high-dose regimens (1.0 mg/kg/day). A critical challenge remains the tapering process; rapid withdrawal triggers inflammatory rebounds, necessitating meticulous, long-lasting (months-years), C-reactive protein (CRP)-guided reductions as small as 5 to 1.25 mg every two to six weeks, similar to the tapering used in polymyalgia rheumatica. Chronic maintenance with low-dose prednisone (≤5 mg/day) may be considered in selected cases, with a good risk-benefit balance. The elderly usually require medium dosages (e.g. prednisone 12.5-25 mg), pregnant women no more than 10 mg, while children should avoid chronic corticosteroid therapy. CRP-negative cases may benefit from low doses (5 mg). Given the long-term duration of therapy, bone protection therapy is essential yet underutilised, while protonpump inhibitors should be used only for concomitant NSAIDs therapy. Corticosteroids are generally ineffective in chronic idiopathic pericardial effusions with normal CRP.In conclusion, modern management redefines corticosteroids as a precision tool rather than a blunt anti-inflammatory agent.
2026-05-27 | Expanding the Therapeutic Landscape of Pericarditis: A Systematic Review of the Use of Conventional Immunosuppressants.
Background and Objectives: While interleukin-1 inhibitors represent the standard of care for refractory idiopathic recurrent acute pericarditis, current guidelines also endorse conventional immunosuppressive (IS) agents as potential alternatives. The use of conventional IS agents is particularly relevant in specific clinical scenarios, such as systemic immune-mediated disease (SID)-associated pericarditis. However, existing evidence regarding their efficacy and safety for pericarditis treatment remains fragmented, deriving exclusively from case reports, case series, and small monocentric observational studies. Our aims are: To characterize the clinical and diagnostic profiles of patients with pericarditis treated with conventional IS agents and to evaluate the therapeutic efficacy and safety of such agents. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines. Major electronic databases were searched from January 1970 to March 2026 for case reports, case series, and observational studies detailing the use of conventional IS therapies for pericarditis. Clinical and therapeutic data, including specific IS indications and dosing regimens, were systematically extracted. Results: The final analysis included 39 reports comprising 75 patients (60% female; median age 36.0 years). The underlying pericarditis aetiology was predominantly SID-related (53%, n = 40) or idiopathic/presumed viral recurrent disease (40%, n = 30). The most frequently prescribed first-line IS agents were azathioprine (44%) and methotrexate (25%). Across published reports, IS therapy was described as achieving pericarditis clinical resolution in all cases and facilitated corticosteroid withdrawal in 72% of patients. Overall, pericarditis recurrence while on IS therapy occurred in only 10% of the cohort. Adverse events requiring IS withdrawal were rare (n = 2, 3%). Conclusions: Conventional IS agents appear effective and generally well tolerated in the published literature on SID-associated and isolated recurrent pericarditis. These findings reinforce the clinical utility of conventional IS therapies as a viable, steroid-sparing strategy when targeted biologic therapies lack sufficient investigation.
2026-05-26 | Recurrent Pericarditis in a Middle-Aged Female with MEFV Mutation.
Recurrent pericarditis (RP) remains challenging, especially in tuberculosis (TB)-endemic regions where empirical anti-TB therapy is often unnecessarily prolonged. We report a 35-year-old woman with three RP episodes over six months, presenting with pleuritic chest pain, elevated inflammatory markers, and moderate-to-large pericardial effusion. Extensive infectious (including TB), autoimmune, and malignancy workups were negative. Cardiac magnetic resonance revealed persistent pericardial late gadolinium enhancement despite clinical remission. Whole-exome sequencing identified a heterozygous MEFV c.442G>C (p.Glu148Gln) variant, suggesting an autoinflammatory predisposition. Although the patient finally achieved sustained symptom-free status for six months on a standardized low-dose colchicine regimen, still over 10% of patients have recurrent symptoms receiving colchicine in addition to conventional anti-inflammatory therapy with aspirin or ibuprofen. This case highlights the shifting paradigm from an infection-centered to an autoinflammatory framework for RP in TB-endemic countries, underscores the role of MEFV variants in idiopathic recurrent pericarditis, and illustrates the real-world gap between genetic insights and therapeutic accessibility to IL-1 inhibitors in resource-limited settings.
2026-03-14 | PERICARDITIS AS A POTENTIAL MARKER OF OCCULT CANCER - A COMPREHENSIVE REVIEW OF EPIDEMIOLOGY, PATHOPHYSIOLOGY AND CLINICAL IMPLICATIONS
Pericarditis, traditionally considered a benign and self-limiting condition, is increasingly recognized as a potential marker of occult malignancy. Epidemiological evidence indicates a significantly increased risk of cancer—particularly lung, hematologic, breast, and gastrointestinal malignancies—within the first year after diagnosis. The association is stronger in elderly patients and in cases of recurrent, idiopathic, or hemorrhagic pericardial effusion. Proposed mechanisms include direct tumor invasion of the pericardium, lymphatic or hematogenous metastasis, and paraneoplastic inflammatory processes. In some patients, pericarditis precedes the diagnosis of cancer by several months, functioning as an early clinical warning sign. When common infectious or autoimmune causes are excluded, further evaluation with advanced imaging, pericardial fluid cytology, and tumor marker analysis is recommended. Maintaining a high index of suspicion in high-risk individuals may enable earlier cancer detection. A structured diagnostic approach and timely oncologic referral are essential to improve clinical outcomes and ensure appropriate management.
antibodies
2026-09-30 | Emerging therapies for pericarditis: from anti-IL-1 agents to novel therapeutic options.
Although often self-limited, acute pericarditis recurs in up to 30% of patients. Recurrent pericarditis (RP) causes substantial morbidity (pain, fatigue, and impaired quality of life) and can lead to constriction. Traditional treatments have important limitations, including corticosteroid dependence, recurrent flares, and treatment-related adverse effects. Emerging targeted immunomodulators are therefore under active investigation. This review summarizes the burden of pericarditis across etiologies, current therapies, and the global market for pericarditis treatment. We then focus on novel agents in development with an emphasis on phase II/III studies. The pathobiology of pericardial inflammation (notably interleukin (IL)-1 and inflammasome pathways) is discussed as the rationale for targeted drugs. We review key trials of IL-1 inhibitors, NLRP3 inhibitors (VTX2735), and other innovations (e.g. cannabidiol-based CardiolRx). Potential obstacles to development are examined. Randomized-withdrawal trials support a marked reduction in recurrences with IL-1 blockade in selected patients with inflammatory, colchicine-resistant and corticosteroid-dependent RP. However, open-label enrichment, small samples, short follow-up, uncertain durability after withdrawal, cost, and limited evidence outside idiopathic or post-cardiac injury disease restrict generalizability. New pipeline agents hold promise for broader use, however remain investigational until controlled trials establish their efficacy and long-term safety.
2026-06-30 | Current issues in the treatment of pericarditis: practical guidelines and pharmacotherapy
The article presents a clinical and pharmacological review of modern approaches to the diagnosis and treatment of pericarditis, with an emphasis on practical recommendations for selecting anti‑inflammatory therapy. The etiological structure of pericardial diseases and the key clinical manifestations of acute, recurrent, and chronic pericarditis are examined. The regimens for using non‑steroidal anti‑inflammatory drugs, colchicine, and glucocorticosteroids are analyzed in detail, along with a comparative assessment of their efficacy and safety. Special attention is paid to the use of interleukin‑1 inhibitors in patients with idiopathic recurrent pericarditis: the results of the COURSE study, dosing regimens for golimumab, and recommendations from experts of the Russian Society of Cardiology are presented. Issues related to the safety of combination therapy with NSAIDs and oral anticoagulants are considered separately. Algorithms for selecting therapy are proposed, depending on the severity of the disease, the response to standard regimens, and the patient’s comorbid background.
2026-05-01 | Case Report: Safety and efficacy of combination therapy with adalimumab and anakinra in two patients with severe inflammatory diseases.
Chronic inflammatory diseases in children can involve distinct immunologic pathways, occasionally necessitating dual biologic therapy when single-agent treatment is insufficient. Evidence on combined IL-1 and TNF-α inhibition remains limited. A 15-year-old girl with ulcerative colitis and recurrent pericarditis received adalimumab and anakinra, achieving clinical remission without infections over eight months. An 11-year-old boy with juvenile idiopathic arthritis, uveitis, and colchicine-resistant familial Mediterranean fever received combined adalimumab and anakinra, achieving low disease activity in both conditions at six months, without adverse events. Dual blockade of TNF-α and IL-1 may be rational in selected patients due to overlapping and complementary roles of these cytokines in driving inflammation. Our cases illustrate that this combination can be effective and well tolerated with careful monitoring. In carefully selected pediatric patients, simultaneous TNF-α and IL-1 inhibition may provide clinical benefit. Further studies are required to assess long-term safety and efficacy.
2025-11-10 | Tolicizumab: a new option for refractory idiopathic recurrent pericarditis: a case report.
Recurrent pericarditis is the most common and troublesome complication of pericarditis and can be particularly challenging when it becomes refractory to conventional therapies, often resulting in a prolonged disease course. Interleukin-1 (IL-1) inhibitors have transformed the management of such cases; however, not all patients tolerate or respond adequately to these agents. We present a 37-year-old man suffering from idiopathic recurrent pericarditis since the age of 25. After failure of standard therapies, he became corticosteroid-dependent, so treatment with anakinra (an IL-1 inhibitor) was attempted twice, but discontinued early due to allergic reactions. As the recurrences were always characterised by an overt inflammatory phenotype (characterised by fever, increased C-reactive protein, and pericardial effusion), we administered off-label tocilizumab (an IL-6 receptor antagonist) as a last treatment option. The patient gained rapid benefit and was able to discontinue steroid therapy during the 6-month follow-up, achieving complete recovery from pericarditis. Interleukin-6 is a key cytokine in the pathogenesis of pericarditis, acting synergistically with IL-1 to drive inflammation and acute phase responses. In our patient, blockade of IL-6 with tocilizumab led to the complete resolution of inflammation, suggesting a possible new therapeutic option for refractory cases. This result highlights the potential of IL-6 inhibition as an alternative strategy, when IL-1 blockers are contraindicated or ineffective.
2025-05-27 | Dual Immunotherapy for Pericardial Mesothelioma That Developed After a Decade-Long Idiopathic Pericarditis: A Case Report.
Malignant pericardial mesothelioma (MPeM) is exceptionally rare, and its association with long-standing idiopathic pericarditis remains unreported. We present a 46-year-old woman with a decade-long history of recurrent idiopathic pericarditis who developed multiple pericardial nodules, mediastinal lymphadenopathy, and metastatic liver and bone lesions. A core needle biopsy confirmed biphasic MPeM. Due to her pericardial condition, she initially received platinum-based chemotherapy instead of immunotherapy, but the disease progressed. She then underwent dual immune checkpoint inhibition (ICI) and achieved a significant clinical and radiological response. This case raises the possibility of chronic inflammation contributing to pericardial malignancy and underscores the potential role of dual ICI in this rare and challenging disease.
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2026-08-14 | Case Report: From idiopathic recurrent pericarditis to systemic Behçet’s Disease: unmasking a unified IL-1-driven autoinflammatory phenotype
Background Recurrent idiopathic recurrent pericarditis (RP) is increasingly recognized as an organ-specific autoinflammatory syndrome driven by the interleukin-1 (IL-1) axis. Behçet’s Disease (BD), a systemic vasculitis, exhibits significant pathogenetic overlap with RP through IL-1 mediated hyperinflammation, particularly in phenotypes dominated by serositis. The clinical evolution of prolonged, seemingly idiopathic RP into overt, systemic BD upon the tapering of targeted therapy remains a critical, yet underreported, observation. Case presentation A 42 years old female with corticosteroid-dependent, colchicine-resistant RP achieved complete and sustained clinical and biochemical remission using the IL-1 receptor antagonist, Anakinra, for almost 30 months, despite the tapering started after 18 months of continuous therapy with Anakinra, associated to colchicine and a quick tapering and withdrawal of corticosteroids. Following the elective tapering of Anakinra, the patient remained stable for three months with a dose of an injection of 100mg of Anakinra three times per week, before suffering a severe pericardial relapse concurrent with the systemic onset of systemic BD. The clinical condition observed fulfilled the International Criteria for Behçet’s Disease (ICBD), featuring recurrent oral and genital ulcerations, erythema nodosum and a positive pathergy test. The immediate reinitiation of Anakinra (100mg daily) led to the rapid and complete resolution of both the pericardial inflammation and all systemic mucocutaneous manifestations. Conclusions This case highlights a potential pathogenetic overlap between refractory RP and serositis-dominant BD phenotypes, suggesting that isolated RP may, in select cases, represent an early mono-organ precursor of a systemic autoinflammatory propensity. Furthermore, it provides clinical rationale for considering IL-1 blockade in serositis-dominant BD, though larger prospective studies are needed to confirm these findings.
2026-08-01 | Recurrent pericarditis in children: evidence, controversies, and emerging perspectives.
Recurrent pericarditis complicates approximately one-third of initial pericarditis episodes in children. Once considered a postinfectious sequel, it is now understood as an autoinflammatory disorder sustained by dysregulated interleukin-1 signaling and inflammasome hyperactivation. This review evaluates therapeutic strategies for idiopathic recurrent pericarditis in patients younger than 18 years using the PICO framework. First-line management with nonsteroidal anti-inflammatory drugs and colchicine remains the therapeutic backbone, with colchicine conferring a roughly 50% reduction in relapse risk. Glucocorticoids, although acutely effective, predispose to steroid-dependence and rebound flares, and should be reserved for refractory disease at low doses. IL-1 receptor antagonism, principally anakinra, has emerged as a transformative steroid-sparing option for colchicine-resistant or steroid-dependent cases, achieving rapid symptom control and durable remission in most treated children. Nonetheless, pediatric evidence remains limited to retrospective cohorts and small case series, highlighting the need for prospective controlled trials, standardized outcome definitions, and long-term safety surveillance of biologic agents.
2026-05-16 | Idiopathic recurrent pericarditis in children: a tertiary care cohort highlighting the emergence and effectiveness of interleukin-1 blockade.
Idiopathic recurrent pericarditis (IRP) is an increasingly recognized inflammatory condition in children, characterized by recurrent flares and therapeutic challenges, with emerging evidence supporting a role for interleukin-1 (IL-1)-mediated pathways. This study aimed to characterize the clinical features of a pediatric IRP cohort at our center, to examine clinically relevant differences between patients requiring and not requiring anakinra, and to evaluate anakinra effectiveness by assessing changes in disease activity before and after treatment. In this single-center retrospective cohort study, 26 children with IRP were evaluated in terms of demographic, clinical, laboratory, genetic, and treatment characteristics. Patients were stratified according to anakinra requirement, and these characteristics were compared between groups. In patients receiving anakinra, treatment effectiveness was assessed by comparing disease activity before and after therapy using annualized attack rate (AAR) and inflammatory markers. The cohort showed a male predominance (19/26, 73%), with a median age at diagnosis of 114 months (IQR, 48-168). Chest pain was the most common presenting symptom (16/26, 62%). Pericardial effusion was present in all patients (26/26, 100%), while pleural effusion was observed in 12/26 (46%). Despite conventional therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids, steroid dependency developed in 9/22 patients (41%). Anakinra was required in 16 patients (62%) and was associated with a marked reduction in disease activity, with a median relative decrease in AAR of 89.4% (IQR, 56.7-100%); a ≥ 50% reduction in AAR was achieved in 12/16 patients (75%). Significant and concordant reductions in inflammatory markers were observed. Relapse frequently occurred during anakinra dose spacing or discontinuation, while corticosteroid withdrawal was achieved in most treated patients. Patients requiring anakinra had higher baseline disease activity. Idiopathic recurrent pericarditis in children represents a heterogeneous and frequently relapsing inflammatory condition in which conventional therapies often fail to achieve sustained disease control. As an IL-1 blockade, anakinra emerges as a key therapeutic option, enabling corticosteroid sparing while effectively achieving disease control through targeting underlying innate immunity pathways. • Idiopathic recurrent pericarditis (IRP) in children is characterized by recurrent inflammatory flares and frequent treatment resistance, with conventional therapies (NSAIDs, colchicine, and corticosteroids) often being insufficient and associated with steroid dependency. • Increasing evidence implicates autoinflammatory pathways in disease pathogenesis, highlighting the potential role of IL-1 inhibition in refractory cases. • The high prevalence of MEFV-associated variants, frequent steroid dependency, and substantial use of IL-1 inhibitors collectively support an auto inflammatory-driven disease model in pediatric IRP. • Anakinra markedly reduces disease activity even in patients with high baseline inflammatory burden; however, sustained disease control requires continuous therapy, as dose spacing is associated with increased relapse rates.
2026-02-28 | Refractory recurrent pericarditis associated with MEFV E148Q variant: selective response to IL-1 receptor antagonism
Interleukin (IL)-1–mediated autoinflammation is increasingly recognised as a driver of recurrent idiopathic pericarditis, particularly in patients with systemic inflammation, glucocorticoid dependence, and suboptimal response to standard therapy, including nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine. Recent studies have shown that low-penetrance variants in autoinflammatory genes such as the Mediterranean fever gene (MEFV) may amplify inflammasome activation, which may underlie treatment resistance in some patients.
2025-11-01 | Rilonacept as monotherapy for long-term recurrent pericarditis management: sustained disease control over three years
Abstract Background Recurrent pericarditis (RP) predominantly shows features consistent with IL-1-mediated chronic autoinflammatory disease (1-4). A recent analysis suggested that supplementing anakinra with colchicine incrementally reduced pericarditis recurrence vs. anakinra alone (5). Rilonacept (a weekly IL-1α and IL-1β cytokine trap with 6-week washout) prevents engagement with IL-1 receptor, inhibiting both IL-1α and IL-1β activity (6). The Phase 3 trial RHAPSODY demonstrated rilonacept efficacy in two independent analyses: Randomized Withdrawal (RW) and Long-Term Extension (LTE) periods (7,8). Purpose Assess long-term recurrence-free persistence with rilonacept as monotherapy in pts with RP during the combined RW and LTE periods of RHAPSODY. Methods Post-hoc analysis. Freedom from recurrence on rilonacept monotherapy was quantified using the Kaplan-Meier (KM) method from RW start (if randomized to rilonacept) or from initiation of bailout rilonacept (if randomized to placebo) until the end of treatment. Prespecified recurrence adjudication criteria were pericarditis pain (numerical rating scale [NRS]) ≥4 plus C-reactive protein (CRP) ≥1 mg/dL. Per RHAPSODY protocol, background therapies were discontinued during the Run-In Period before randomization. In pts treated with rilonacept, concomitant colchicine was not added during the RW period. In the LTE, 6.8% (5/74) of pts added colchicine: one for 2 days of chest pain without CRP elevation, 4 in the absence of chest pain, CRP elevation, or recurrence; these 5 pts were censored in the KM curve at 6 days after last rilonacept dose or at colchicine initiation (whichever was first). One additional pt added colchicine prophylactically before an intentional rilonacept treatment interruption for elective cardiac surgery and experienced a recurrence after this interruption; this pt was not censored from the recurrence-free persistence analysis at colchicine initiation in order to capture this event. Results 74 pts (mean [SD] age 43.9 [15.7] years, 83.8% idiopathic pericarditis, mean [SD] disease duration 2.5 [3.2] years) were analyzed over three years. Rilonacept was well tolerated. Recurrence-free persistence was 95.9% (n=71/74) while receiving rilonacept as monotherapy (Figure 1). The three observed adjudicated recurrences were each associated with temporary interruptions of 1-3 doses of rilonacept. Conclusions Rilonacept as monotherapy provided recurrence-free persistence over the three-year trial duration when used continuously without interruption; pericarditis recurrences occurred only after interruptions. These findings support evidence-based use of rilonacept as monotherapy, minimizing the need for adjunctive treatments and reducing polypharmacy in long-term RP management. Further investigations are warranted to address how to assess pts as candidates for long-term treatment with rilonacept and when to cease rilonacept treatment.
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Drug Discovery Landscape
9 orphan drug designations for Idiopathic recurrent pericarditis, including 1 approved therapy.
9 orphan drug designations for Idiopathic recurrent pericarditis, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
peripherally restricted, selective, small molecule inhibitor of NLRP3 (NLR [nucleotide-binding domain and leucine-rich repeat] family, pyrin domain containing 3) | small molecules | FDA | Zomagen Biosciences Ltd, a wholly owned subsidiary of Ventyx Biosciences, Ltd. | |
colchicine | small molecules | FDA | Pharmascience Inc. | |
fully human IgG2 monoclonal antibody that blocks interleukin-1 receptor 1 | antibodies | FDA | Kiniksa Pharmaceuticals,GmbH,c/o Kiniksa Pharmaceuticals Corp | |
colchicine | small molecules | FDA | Scilex Pharmaceuticals Inc. | |
goflikicept | proteins | FDA | R-Pharm Overseas, Inc. | |
colchicine | small molecules | FDA | ACARPIA Farmaceutici S.r.l. | |
Cannabidiol | small molecules | FDA | Cardiol Therapeutics Inc. | |
Rilonacept | proteins | EMA | FGK Representative Service GmbH | |
rilonacept [Arcalyst] | proteins | FDA | Approved | Kiniksa Pharmaceuticals, Ltd. |
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